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1. Gil L, Styczynski J, Dytfeld D, Debski R, Kazmierczak M, Kolodziej B, Rafinska B, Kubicka M, Nowicki A, Komarnicki M, Wysocki M: Activity of bortezomib in adult de novo and relapsed acute myeloid leukemia. Anticancer Res; 2007 Nov-Dec;27(6B):4021-5
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  • [Title] Activity of bortezomib in adult de novo and relapsed acute myeloid leukemia.
  • AIM: The aim of the study was the analysis of in vitro drug resistance to bortezomib and other anticancer drugs in de novo and relapsed adult acute myeloid leukemia (AML).
  • PATIENTS AND METHODS: The leukemic cells of 46 adult patients with AML were tested for the in vitro drug resistance profile.
  • The group included 20 de novo and 26 relapsed AML patients, among whom, 12 relapsed after allogeneic hematopoietic stem cell transplantation (HSCT) and 4 after autologous HSCT.
  • RESULTS: No significant differences in drug resistance were found for all tested drugs between de novo and relapsed AML samples, while expression of PGP, MRP1 and LRP was higher in relapsed patients.
  • Patients with refractory or relapsed disease, had higher resistance of myeloblasts to cyclophosphamide (RR = 2.4, p = 0.050), and better sensitivity to busulfan (RR = 0.4, p = 0.054) and topotecan (RR = 0.4, p = 0.031).
  • Those who have died due to refractory/relapsed disease (n = 16) had better sensitivity to bortezomib (RR = 0.6, p = 0.046) and treosulfan (RR = 0.1, p = 0.018).
  • CONCLUSION: In vitro drug resistance in relapsed adult AML is comparable to that in de novo disease.
  • Activity in vitro of bortezomib might be a rationale for its use in refractory/relapsed AML adult patients.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Boronic Acids / pharmacology. Leukemia, Myeloid / drug therapy. Pyrazines / pharmacology
  • [MeSH-minor] Acute Disease. Adolescent. Adult. Aged. Bortezomib. Drug Resistance, Neoplasm. Female. Flow Cytometry. HL-60 Cells. Humans. Male. Middle Aged. Multidrug Resistance-Associated Proteins / biosynthesis. Multidrug Resistance-Associated Proteins / metabolism. P-Glycoprotein / biosynthesis. P-Glycoprotein / metabolism. Vault Ribonucleoprotein Particles / biosynthesis. Vault Ribonucleoprotein Particles / metabolism

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  • (PMID = 18225565.001).
  • [ISSN] 0250-7005
  • [Journal-full-title] Anticancer research
  • [ISO-abbreviation] Anticancer Res.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Greece
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Boronic Acids; 0 / Multidrug Resistance-Associated Proteins; 0 / P-Glycoprotein; 0 / Pyrazines; 0 / Vault Ribonucleoprotein Particles; 0 / major vault protein; 0 / multidrug resistance-associated protein 1; 69G8BD63PP / Bortezomib
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2. Mao G, Yuan F, Absher K, Jennings CD, Howard DS, Jordan CT, Gu L: Preferential loss of mismatch repair function in refractory and relapsed acute myeloid leukemia: potential contribution to AML progression. Cell Res; 2008 Feb;18(2):281-9
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  • [Title] Preferential loss of mismatch repair function in refractory and relapsed acute myeloid leukemia: potential contribution to AML progression.
  • Acute myeloid leukemia (AML) is an aggressive hematological cancer.
  • The molecular mechanisms underlying AML development and relapse remain incompletely defined.
  • To explore whether loss of DNA mismatch repair (MMR) function is involved in AML, we screened two key MMR genes, MSH2 and MLH1, for mutations and promoter hypermethylation in leukemia specimens from 53 AML patients and blood from 17 non-cancer controls.
  • We show here that whereas no amino acid alteration or promoter hypermethylation was detected in all control samples, 18 AML patients exhibited either mutations in MMR genes or hypermethylation in the MLH1 promoter.
  • MMR defects were significantly more frequent in patients with refractory or relapsed AML compared with newly diagnosed patients.
  • These observations suggest for the first time that the loss of MMR function is associated with refractory and relapsed AML and may contribute to disease pathogenesis.
  • [MeSH-major] Adaptor Proteins, Signal Transducing / genetics. DNA Methylation. DNA Mismatch Repair. Leukemia, Myeloid, Acute / genetics. MutS Homolog 2 Protein / genetics. Mutation. Neoplasm Proteins / genetics. Nuclear Proteins / genetics
  • [MeSH-minor] Adolescent. Adult. Aged. Aged, 80 and over. Child. Child, Preschool. Female. Humans. Infant. Male. Middle Aged. Promoter Regions, Genetic / genetics. Recurrence

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  • (PMID = 18227862.001).
  • [ISSN] 1748-7838
  • [Journal-full-title] Cell research
  • [ISO-abbreviation] Cell Res.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA104333
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Adaptor Proteins, Signal Transducing; 0 / MLH1 protein, human; 0 / Neoplasm Proteins; 0 / Nuclear Proteins; EC 3.6.1.3 / MSH2 protein, human; EC 3.6.1.3 / MutS Homolog 2 Protein
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3. Middeldorf I, Galm O, Osieka R, Jost E, Herman JG, Wilop S: Sequence of administration and methylation of SOCS3 may govern response to gemtuzumab ozogamicin in combination with conventional chemotherapy in patients with refractory or relapsed acute myelogenous leukemia (AML). Am J Hematol; 2010 Jul;85(7):477-81
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  • [Title] Sequence of administration and methylation of SOCS3 may govern response to gemtuzumab ozogamicin in combination with conventional chemotherapy in patients with refractory or relapsed acute myelogenous leukemia (AML).
  • In older patients suffering from acute myelogenous leukemia (AML), aggressive chemotherapy is accompanied with high treatment-related morbidity and mortality.
  • Consequently, a variable response of AML cells to anti-CD33-targeted therapy may be caused by modulation of SOCS3 expression.
  • Twenty-four patients with refractory or relapsed CD33-positive AML received GO as a single agent before or after conventional chemotherapy.
  • [MeSH-major] Aminoglycosides / administration & dosage. Antibodies, Monoclonal / administration & dosage. DNA Methylation. Leukemia, Myeloid, Acute / drug therapy. Salvage Therapy / methods. Suppressor of Cytokine Signaling Proteins / genetics
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Antibodies, Monoclonal, Humanized. Antineoplastic Combined Chemotherapy Protocols / administration & dosage. CpG Islands. Drug Administration Schedule. Humans. Middle Aged. Retrospective Studies. Survival Rate. Treatment Outcome

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  • [Copyright] (c) 2010 Wiley-Liss, Inc.
  • (PMID = 20575043.001).
  • [ISSN] 1096-8652
  • [Journal-full-title] American journal of hematology
  • [ISO-abbreviation] Am. J. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Aminoglycosides; 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / SOCS3 protein, human; 0 / Suppressor of Cytokine Signaling Proteins; 0 / gemtuzumab
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4. Seiter K, Katragadda S, Ponce D, Rasul M, Ahmed N: Temozolomide and cisplatin in relapsed/refractory acute leukemia. J Hematol Oncol; 2009;2:21
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  • [Title] Temozolomide and cisplatin in relapsed/refractory acute leukemia.
  • Cisplatin depletes MGMT and increases the sensitivity of leukemia cells to temozolomide.
  • We performed a phase I study of cisplatin and temozolomide in patients with relapsed and refractory acute leukemia.
  • Fifteen patients had AML, 3 had ALL, and 2 had biphenotypic leukemia.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cisplatin / administration & dosage. Dacarbazine / analogs & derivatives. Leukemia, Myeloid, Acute / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • [MeSH-minor] Adult. Aged. Drug Resistance, Neoplasm / drug effects. Female. Humans. Male. Middle Aged. Recurrence. Salvage Therapy. Treatment Failure. Young Adult

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  • (PMID = 19463179.001).
  • [ISSN] 1756-8722
  • [Journal-full-title] Journal of hematology & oncology
  • [ISO-abbreviation] J Hematol Oncol
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 7GR28W0FJI / Dacarbazine; 85622-93-1 / temozolomide; Q20Q21Q62J / Cisplatin
  • [Other-IDs] NLM/ PMC2694825
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5. Kaspers GJ, Reinhardt D, Fleischhack G, Armendariz H, Stark B, Zwaan CM, Zimmermann M, Creutzig U: Low efficacy of methotrexate in childhood acute myeloid leukemia (AML): single-agent therapeutic window study in relapsed AML. Pediatr Blood Cancer; 2006 Oct 15;47(5):539-42
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  • [Title] Low efficacy of methotrexate in childhood acute myeloid leukemia (AML): single-agent therapeutic window study in relapsed AML.
  • BACKGROUND: The efficacy in pediatric acute myeloid leukemia (AML) of single-agent methotrexate (MTX) at a higher dose than previously applied, 1,000 mg/m2, given as a theoretically beneficial 36-hr continuous infusion, is unknown, but may be beneficial based on preclinical data.
  • PROCEDURE: We performed a therapeutic window study in children with first relapsed AML treated in four different countries.
  • By that time, another four patients had been enrolled, of which one patient with a late relapsed AML FAB type M7 showed a good response.
  • CONCLUSIONS: This study shows that single-agent MTX in the applied regimen in pediatric relapsed AML has limited efficacy.
  • However, it also demonstrates the feasibility of an international and therapeutic window phase II study in pediatric relapsed AML.
  • [MeSH-major] Leukemia, Myeloid, Acute / drug therapy. Methotrexate / therapeutic use
  • [MeSH-minor] Adolescent. Adult. Child. Child, Preschool. Dose-Response Relationship, Drug. Female. Humans. Infant. Infusions, Intravenous. Male. Maximum Tolerated Dose. Recurrence. Treatment Outcome


6. Blum W, Klisovic RB, Becker H, Yang X, Rozewski DM, Phelps MA, Garzon R, Walker A, Chandler JC, Whitman SP, Curfman J, Liu S, Schaaf L, Mickle J, Kefauver C, Devine SM, Grever MR, Marcucci G, Byrd JC: Dose escalation of lenalidomide in relapsed or refractory acute leukemias. J Clin Oncol; 2010 Nov 20;28(33):4919-25
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  • [Title] Dose escalation of lenalidomide in relapsed or refractory acute leukemias.
  • We report results of a phase I dose-escalation trial of lenalidomide in relapsed or refractory acute leukemia.
  • PATIENTS AND METHODS: Thirty-one adults with acute myeloid leukemia (AML) and four adults with acute lymphoblastic leukemia (ALL) were enrolled.
  • In AML, five (16%) of 31 patients achieved complete remission (CR); three of three patients with cytogenetic abnormalities achieved cytogenetic CR (none with deletion 5q).
  • All responses occurred in AML with low presenting WBC count.
  • Two of four patients who received lenalidomide as initial therapy for AML relapse after allogeneic transplantation achieved durable CR after development of cutaneous graft-versus-host disease, without donor leukocyte infusion.
  • CONCLUSION: Lenalidomide was safely escalated to 50 mg daily for 21 days, every 4 weeks, and was active with relatively low toxicity in patients with relapsed/refractory AML.
  • Remissions achieved after transplantation suggest a possible immunomodulatory effect of lenalidomide, and results provide enthusiasm for further studies in AML, either alone or in combination with conventional agents or other immunotherapies.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Leukemia, Myeloid, Acute / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Thalidomide / analogs & derivatives
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Antigens, CD / analysis. Antigens, Differentiation, Myelomonocytic / analysis. Humans. Middle Aged. Recurrence. Sialic Acid Binding Ig-like Lectin 3

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  • (PMID = 20956622.001).
  • [ISSN] 1527-7755
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / P50 CA140158; United States / NCI NIH HHS / CA / K23 CA120708; United States / NCI NIH HHS / CA / P50-CA140158; United States / NCI NIH HHS / CA / K23CA120708; United States / NCRR NIH HHS / RR / UL1 RR025755; United States / NCI NIH HHS / CA / P30 CA016058
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, CD; 0 / Antigens, Differentiation, Myelomonocytic; 0 / Antineoplastic Agents; 0 / CD33 protein, human; 0 / Sialic Acid Binding Ig-like Lectin 3; 4Z8R6ORS6L / Thalidomide; F0P408N6V4 / lenalidomide
  • [Other-IDs] NLM/ PMC3020696
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7. Camera A, Rinaldi CR, Palmieri S, Cantore N, Mele G, Mettivier V, Miraglia E, Mastrullo L, Grimaldi F, Luciano L, Guerriero A, Rotoli B, Ferrara F: Sequential continuous infusion of fludarabine and cytarabine associated with liposomal daunorubicin (DaunoXome) (FLAD) in primary refractory or relapsed adult acute myeloid leukemia patients. Ann Hematol; 2009 Feb;88(2):151-8
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  • [Title] Sequential continuous infusion of fludarabine and cytarabine associated with liposomal daunorubicin (DaunoXome) (FLAD) in primary refractory or relapsed adult acute myeloid leukemia patients.
  • A large proportion of adult patients with acute myeloid leukemia (AML) relapse after treatment, and some of them are resistant to primary induction chemotherapy.
  • Sixty-one patients from seven hematological centers with poor-risk AML, primary refractory (n = 16), or relapsed (n = 45) were treated with a salvage regimen, including fludarabine (2 days) and cytarabine (3 days) in a sequential continuous infusion, associated with liposomal daunorubicin (3 days) (FLAD).
  • Complete response rate was 44% and 56% for refractory and relapsed patients, respectively, with an overall response rate of 52% (32 of 61).
  • Twenty patients (62.5%) relapsed after this treatment in a median of 7.3 months; ten patients relapsed after a SCT procedure.
  • A better response rate was obtained in the subgroup of relapsed patients, compared to patients treated for refractory disease.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cytarabine / therapeutic use. Daunorubicin / administration & dosage. Daunorubicin / therapeutic use. Leukemia, Myeloid, Acute / drug therapy. Vidarabine / analogs & derivatives
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Disease-Free Survival. Female. Humans. Infusions, Intravenous. Liposomes. Male. Middle Aged. Recurrence. Salvage Therapy. Stem Cell Transplantation. Survival Rate. Time Factors

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  • (PMID = 18709502.001).
  • [ISSN] 1432-0584
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Liposomes; 04079A1RDZ / Cytarabine; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine; ZS7284E0ZP / Daunorubicin
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8. Das-Gupta EP, Russell NH, Shaw BE, Pearce RM, Byrne JL: Long-term outcome of unrelated donor transplantation for AML using myeloablative conditioning incorporating pretransplant Alemtuzumab. Biol Blood Marrow Transplant; 2007 Jun;13(6):724-33
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  • [Title] Long-term outcome of unrelated donor transplantation for AML using myeloablative conditioning incorporating pretransplant Alemtuzumab.
  • The outcome of 55 patients who underwent matched unrelated donor (MUD) transplantation for acute myelogenous leukemia (AML) following a conditioning regimen of cyclophosphamide and total-body irradiation (TBI) with the addition of Alemtuzumab 10 mg/kg/day on days -5 to -1 is described.
  • The group consisted of adult patients with a median age of 37 years.
  • Grade II-IV acute GVHD occurred in only 2 patients.
  • These results support the use of Alemtuzumab for unrelated donor hematopoietic stem cell transplant (HSCT) for poor risk AML in CR1 and for relapsed AML in CR2.
  • The addition of Alemtuzumab is highly effective in preventing both rejection and severe acute and extensive chronic GVHD without an increased relapse risk.
  • [MeSH-major] Antibodies, Monoclonal / administration & dosage. Antibodies, Neoplasm / administration & dosage. Hematopoietic Stem Cell Transplantation / methods. Leukemia, Myeloid / therapy. Transplantation Conditioning / methods
  • [MeSH-minor] Acute Disease. Adolescent. Adult. Antibodies, Monoclonal, Humanized. Cause of Death. Cyclophosphamide / therapeutic use. Female. Graft Rejection / prevention & control. Graft vs Host Disease / prevention & control. Histocompatibility Testing. Humans. Longitudinal Studies. Male. Middle Aged. Myeloablative Agonists / therapeutic use. Survival Analysis. Tissue Donors. Treatment Outcome. Whole-Body Irradiation

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  • (PMID = 17531783.001).
  • [ISSN] 1083-8791
  • [Journal-full-title] Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • [ISO-abbreviation] Biol. Blood Marrow Transplant.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antibodies, Neoplasm; 0 / Myeloablative Agonists; 3A189DH42V / alemtuzumab; 8N3DW7272P / Cyclophosphamide
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9. Xu J, Xu CG, Liu T, Xiang B, Chang H, He C: [A clinical trial for homoharringtonine and low-dose cytosine arabinoside combined with G-CSF or GM-CSF to treat the relapsed or refractory acute myeloid leukemia (AML), geriatric AML and advanced myelodysplastic syndromes]. Sichuan Da Xue Xue Bao Yi Xue Ban; 2009 Jan;40(1):129-32
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  • [Title] [A clinical trial for homoharringtonine and low-dose cytosine arabinoside combined with G-CSF or GM-CSF to treat the relapsed or refractory acute myeloid leukemia (AML), geriatric AML and advanced myelodysplastic syndromes].
  • OBJECTIVE: To evaluate the effectiveness and toxicity of the regimen combined homoharringtonine, low-dose cytarabine with G-CSF or GM-CSF (HAG regimen) in treating patients with relapsed or refractory AML, geriatric AML and advanced myelodysplastic syndromes (MDS).
  • METHODS: Forty patients with AML or advanced MDS were treated with HAG regimen for remission induction and consolidation therapy.
  • Results 20 of them (50%) achieved complete remission (CR), including 46.2% patients with relapsed or refractory AML, 60% elderly patients with primary AML who were either untreated or treated with only one course of induction therapy previously, and 66.7% patients with MDS-RAEB.
  • Non-hematologic adverse effects were minimal.
  • It seems promising for the treatment of relapsed or refractory AML, geriatric AML and advanced MDS.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Granulocyte Colony-Stimulating Factor / administration & dosage. Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage. Leukemia, Myeloid, Acute / drug therapy. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Aged, 80 and over. Cytarabine / administration & dosage. Female. Follow-Up Studies. Harringtonines / administration & dosage. Humans. Male. Middle Aged. Neoplasm Recurrence, Local / drug therapy. Young Adult


10. Cloos J, Goemans BF, Hess CJ, van Oostveen JW, Waisfisz Q, Corthals S, de Lange D, Boeckx N, Hählen K, Reinhardt D, Creutzig U, Schuurhuis GJ, Zwaan ChM, Kaspers GJ: Stability and prognostic influence of FLT3 mutations in paired initial and relapsed AML samples. Leukemia; 2006 Jul;20(7):1217-20
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  • [Title] Stability and prognostic influence of FLT3 mutations in paired initial and relapsed AML samples.
  • In acute myeloid leukemia (AML), activating mutations in the fms-like tyrosine kinase 3 (FLT3) gene predict poor prognosis.
  • We determined FLT3 internal tandem duplications (FLT3/ITD) and D835 point mutations in paired initial and relapse samples from 80 pediatric and adult AML patients.
  • One D835 point mutation was found in an initial pediatric AML sample.
  • [MeSH-major] Leukemia, Myeloid, Acute / epidemiology. Leukemia, Myeloid, Acute / genetics. Point Mutation. fms-Like Tyrosine Kinase 3 / genetics
  • [MeSH-minor] Adolescent. Adult. Female. Genetic Markers. Genetic Predisposition to Disease / epidemiology. Humans. Leukemia, Erythroblastic, Acute / genetics. Leukemia, Megakaryoblastic, Acute / genetics. Leukemia, Monocytic, Acute / genetics. Leukemia, Myelomonocytic, Acute / genetics. Leukemia, Promyelocytic, Acute / genetics. Male. Neoplasm, Residual / epidemiology. Neoplasm, Residual / genetics. Prognosis. Recurrence. Risk Factors. Tandem Repeat Sequences

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  • (PMID = 16642044.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Genetic Markers; EC 2.7.10.1 / FLT3 protein, human; EC 2.7.10.1 / fms-Like Tyrosine Kinase 3
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11. Locke FL, Artz A, Rich E, Zhang Y, van Besien K, Stock W: Feasibility of clofarabine cytoreduction before allogeneic transplant conditioning for refractory AML. Bone Marrow Transplant; 2010 Dec;45(12):1692-8
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  • [Title] Feasibility of clofarabine cytoreduction before allogeneic transplant conditioning for refractory AML.
  • To control disease before allogeneic hematopoietic cell transplantation (HCT) for relapsed/refractory AML, we used clofarabine cytoreduction.
  • Nine patients relapsed.
  • Outcomes for this cohort of patients with refractory AML remain poor and we are studying this approach in a prospective manner.
  • [MeSH-major] Adenine Nucleotides / therapeutic use. Antineoplastic Agents / therapeutic use. Arabinonucleosides / therapeutic use. Hematopoietic Stem Cell Transplantation / methods. Leukemia, Myeloid, Acute / drug therapy. Transplantation Conditioning / methods
  • [MeSH-minor] Adolescent. Adult. Aged. Combined Modality Therapy. Female. Humans. Male. Middle Aged. Retrospective Studies. Treatment Outcome. Young Adult

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  • (PMID = 20208570.001).
  • [ISSN] 1476-5365
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / K24 CA116471
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Adenine Nucleotides; 0 / Antineoplastic Agents; 0 / Arabinonucleosides; 762RDY0Y2H / clofarabine
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12. Walker AR, Komrokji RS, Ifthikharuddin J, Messina P, Mulford D, Becker M, Friedberg J, Oliva J, Phillips G, Liesveld JL, Abboud C: Phase I study of cladribine, cytarabine (Ara-C), granulocyte colony stimulating factor (G-CSF) (CLAG Regimen) and simultaneous escalating doses of imatinib mesylate (Gleevec) in relapsed/refractory AML. Leuk Res; 2008 Dec;32(12):1830-6
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  • [Title] Phase I study of cladribine, cytarabine (Ara-C), granulocyte colony stimulating factor (G-CSF) (CLAG Regimen) and simultaneous escalating doses of imatinib mesylate (Gleevec) in relapsed/refractory AML.
  • Receptor activated tyrosine kinases such as c-kit, c-fms and PDGFR are known targets of inhibition by imatinib mesylate (Gleevec) and are expressed on AML blasts.
  • Given the synergy in vitro between Ara-C and imatinib mesylate on AML cell growth inhibition, we initiated a Phase I study combining CLAG+imatinib mesylate in AML patients.
  • Patients with relapsed, refractory AML or CML myeloid blast crisis were eligible to receive Cladribine 5mg/m(2) days 3-7, Cytarabine 2gm/m(2) days 3-7, G-CSF 300mcg days 2-7, and escalating doses of imatinib mesylate given on days 1-15.
  • A total of 16 patients were enrolled, 15 AML and 1 CML myeloid blast crisis.
  • [MeSH-major] Antineoplastic Agents / toxicity. Antineoplastic Combined Chemotherapy Protocols / toxicity. Leukemia, Myeloid, Acute / drug therapy. Piperazines / therapeutic use. Pyrimidines / therapeutic use
  • [MeSH-minor] Adult. Aged. Benzamides. Blast Crisis / chemically induced. Bone Marrow / drug effects. Bone Marrow / pathology. Cladribine / administration & dosage. Cytarabine / administration & dosage. Disease-Free Survival. Dose-Response Relationship, Drug. Drug Administration Schedule. Female. Granulocyte Colony-Stimulating Factor / administration & dosage. Humans. Imatinib Mesylate. Male. Middle Aged. Recurrence. Time Factors

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  • (PMID = 18571721.001).
  • [ISSN] 0145-2126
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 47M74X9YT5 / Cladribine; 8A1O1M485B / Imatinib Mesylate; CLAG protocol
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13. Giles FJ, O'Brien S, Rizzieri DA, Vey N, Krug U, Sekeres M, Jacobsen TF, Nilsson BI, Staudacher K: A phase II study with CP-4055 in patients with second salvage AML. J Clin Oncol; 2009 May 20;27(15_suppl):7047

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] A phase II study with CP-4055 in patients with second salvage AML.
  • The aim of this study was to assess efficacy and safety of CP-4055 when given as second salvage therapy to patients (pts) with acute myeloid leukemia (AML).
  • METHODS: Adult pts who received two previous chemotherapy regimens and who had refractory/relapsed AML (CR after first salvage therapy lasting less than 6 months) were enrolled.
  • Clinical activity (IWG criteria for AML), 2 CR (1 with no CR1 or CR2), and 1 CRp (CR rate 15%), were reported.
  • CONCLUSIONS: CP-4055 given as second salvage therapy to AML pts show manageable toxicity when administered at 2,000 mg/m<sup>2</sup>/d, 24 h CIV, in a d1-5 q3w schedule.
  • Clinical activity (2 CR and 1 CRp) has been reported among the first 20 late stage AML pts.

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  • (PMID = 27961426.001).
  • [ISSN] 1527-7755
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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14. McHayleh WM, Redner R, Sehgal R, Raptis A, Agha M, Natale J, Luong T, Schlesselman JJ, Foon K, Boyiadzis M: Etoposide and mitoxantrone in newly diagnosed acute myeloid leukemia patients with persistent leukemia after a course of induction therapy with cytarabine and idarubicin. J Clin Oncol; 2009 May 20;27(15_suppl):7073

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Etoposide and mitoxantrone in newly diagnosed acute myeloid leukemia patients with persistent leukemia after a course of induction therapy with cytarabine and idarubicin.
  • : 7073 Background: The goal of induction chemotherapy in acute myeloid leukemia (AML) is complete remission with restoration of normal bone marrow.
  • If residual leukemia is present after the first course of induction therapy, patients receive a second course identical to the first or receive a non-cross resistant antileukemic regimen.
  • METHODS: In a retrospective study of adult patients with newly-diagnosed AML treated at the University of Pittsburgh Cancer Institute between December 2002 and May 2008, we evaluated the efficacy and toxicity of mitoxantrone (10 mg/m<sup>2</sup>/d) and etoposide (100 mg/m<sup>2</sup>/d), both administered intravenously within 5 days as second course therapy of patients not responding to first-course induction therapy with cytarabine and idarubicin.
  • RESULTS: 74 AML patients (mean age 56 years, range: 18-73 years) completed treatment with etoposide and mitoxantrone; 29 (39%) achieved CR.
  • The 29 patients who achieved CR received postremission therapy: 16 of these eventually relapsed, while 4 others died without evidence of relapse.
  • CONCLUSIONS: Our study suggests that the combination of etoposide and mitoxantorne is an active and well-tolerated regimen as second-course therapy in newly diagnosed AML patients who have persistent leukemia after a first course of induction therapy with cytarabine and idarubicin.

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  • (PMID = 27961456.001).
  • [ISSN] 1527-7755
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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15. Li S, Wang T, Wang J, Li J, Zhang L: [Dynamic detection of FLT3 gene in patients with AML and its significance]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2007 Aug;15(4):705-8
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  • [Title] [Dynamic detection of FLT3 gene in patients with AML and its significance].
  • Minimal residual disease (MRD) is an important cause of relapse and disease-free survival time decrease in patients with acute myeloid leukemia (AML).
  • This study was aimed to explore the role of FLT3 gene in AML pathogenesis and its significanse for detection of MRD.
  • Using genomic PCR, 125 AML patients were detected for FLT3 gene expression before and after chemical therapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT), meantime the AML patients with FLT3 positive expression were observed by follow-up.
  • The results showed that the sensitivity of PCR was 10(-4) in FLT3 gene detection; the rates of FLT3 positive expression were 69.6% and 44.90% in the newly diagnosed AML patients and complete remission (CR) patients respectively.
  • The rate of FLT3 expression coverted to negative was 48.98% in treated AML patients, while no change of FLT 3 expression was found in 6.12% treated patients.
  • The FLT3 expression converted to positive in relapsed patients, and FLT3 expression remains positive in non-remitted patients.
  • The AML relapse rate in FLT3 positive patients was significantly higher than that in FLT3 negative expression patients (p < 0.05).
  • It is concluded that FLT3 gene expression is related to leukemia pathogenesis; the dynamic levels of FLT3 expression before and after treatment can be used for estimating prognosis of AML patients and detecting MRD.

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  • (PMID = 17708787.001).
  • [ISSN] 1009-2137
  • [Journal-full-title] Zhongguo shi yan xue ye xue za zhi
  • [ISO-abbreviation] Zhongguo Shi Yan Xue Ye Xue Za Zhi
  • [Language] CHI
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; EC 2.7.10.1 / FLT3 protein, human; EC 2.7.10.1 / fms-Like Tyrosine Kinase 3
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16. Wang ES, Sait SN, Gold D, Mashtare T, Starostik P, Ford LA, Wetzler M, Nowak NJ, Deeb G: Genomic, immunophenotypic, and NPM1/FLT3 mutational studies on 17 patients with normal karyotype acute myeloid leukemia (AML) followed by aberrant karyotype AML at relapse. Cancer Genet Cytogenet; 2010 Oct 15;202(2):101-7
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  • [Title] Genomic, immunophenotypic, and NPM1/FLT3 mutational studies on 17 patients with normal karyotype acute myeloid leukemia (AML) followed by aberrant karyotype AML at relapse.
  • Normal karyotype (NK) is the most common cytogenetic group in acute myeloid leukemia (AML) diagnosis; however, up to 50% of these patients at relapse will have aberrant karyotype (AK) AML.
  • To determine the etiology of relapsed AK AML cells, we evaluated cytogenetic, immunophenotypic, and molecular results of 17 patients with diagnostic NK AML and relapsed AK AML at our institute.
  • AK AML karyotype was diverse, involving no favorable and largely (8 of 17) complex cytogenetics.
  • High-resolution array-based comparative genomic hybridization (aCGH) performed via paired aCGH on NK AML and AK AML samples from the same patient confirmed cytogenetic aberrations only in the relapse sample.
  • Analysis of 16 additional diagnostic NK AML samples revealed no evidence of submicroscopic aberrations undetected by conventional cytogenetics in any case.
  • These results favor evolution of NK AML leukemia cells with acquisition of novel genetic changes as the most common etiology of AK AML relapse as opposed to secondary leukemogenesis.
  • Additional studies are needed to confirm whether AK AML cells represent selection of rare preexisting clones below aCGH detection and to further characterize the molecular lesions found at time of AK AML relapse.
  • [MeSH-major] Genomics. Immunophenotyping. Leukemia, Myeloid, Acute / enzymology. Leukemia, Myeloid, Acute / genetics. Nuclear Proteins / genetics. fms-Like Tyrosine Kinase 3 / genetics
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Chromosome Aberrations. Comparative Genomic Hybridization. DNA Mutational Analysis. Female. Humans. Karyotyping. Male. Middle Aged. Recurrence. Treatment Outcome. Young Adult

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  • [Copyright] Copyright © 2010 Elsevier Inc. All rights reserved.
  • (PMID = 20875872.001).
  • [ISSN] 1873-4456
  • [Journal-full-title] Cancer genetics and cytogenetics
  • [ISO-abbreviation] Cancer Genet. Cytogenet.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA016156
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Nuclear Proteins; 117896-08-9 / nucleophosmin; EC 2.7.10.1 / fms-Like Tyrosine Kinase 3
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17. Bruserud Ø, Stapnes C, Tronstad KJ, Ryningen A, Anensen N, Gjertsen BT: Protein lysine acetylation in normal and leukaemic haematopoiesis: HDACs as possible therapeutic targets in adult AML. Expert Opin Ther Targets; 2006 Feb;10(1):51-68
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  • [Title] Protein lysine acetylation in normal and leukaemic haematopoiesis: HDACs as possible therapeutic targets in adult AML.
  • Several new therapeutic strategies are now considered for acute myelogenous leukaemia (AML), including modulation of protein lysine acetylation through inhibition of histone deacetylases (HDACs): a large group of enzymes that alters the acetylation and, thereby, the function of a wide range of nuclear and cytoplasmic proteins.
  • The only HDAC inhibitors that have been investigated in clinical studies of AML are butyrate derivatives, valproic acid and depsipeptide.
  • In the first studies, the drugs have usually been used as continuous therapy for several weeks or months, and in most studies the drugs were used alone or in combination with all-trans retinoic acid for treatment of patients with relapsed or primary resistant AML.
  • Complete haematological remission lasting for several months has been reported for a few patients (< 5% of included patients), whereas increased peripheral blood platelet counts seem more common and have been described both for patients with AML and myelodysplastic syndromes.
  • Taken together, these studies suggest that HDAC inhibition can mediate antileukaemic effects in AML, but for most patients the clinical benefit seems limited and further studies of combination therapy are required.
  • [MeSH-major] Drug Delivery Systems / methods. Hematopoiesis / drug effects. Histone Deacetylases / metabolism. Leukemia, Myeloid, Acute / drug therapy. Leukemia, Myeloid, Acute / enzymology. Lysine / metabolism
  • [MeSH-minor] Acetylation / drug effects. Adult. Antineoplastic Agents / therapeutic use. Enzyme Inhibitors / therapeutic use. Histone Deacetylase Inhibitors. Humans

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  • (PMID = 16441228.001).
  • [ISSN] 1744-7631
  • [Journal-full-title] Expert opinion on therapeutic targets
  • [ISO-abbreviation] Expert Opin. Ther. Targets
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Enzyme Inhibitors; 0 / Histone Deacetylase Inhibitors; EC 3.5.1.98 / Histone Deacetylases; K3Z4F929H6 / Lysine
  • [Number-of-references] 136
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18. Wu XX, Da WM, Li HH, Zhao Y, Wang QS, Wang SH, Zhu HY: [Effects of FLAG regimen in treatment of refractory or relapsed acute myeloid leukemia]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2005 Jun;13(3):394-6
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  • [Title] [Effects of FLAG regimen in treatment of refractory or relapsed acute myeloid leukemia].
  • In order to evaluate the effects of FLAG regimen in treatment of refractory and relapsed acute myeloid leukemia (AML), 27 patients with refractory or relapsed acute myeloid leukemia (10 refractory AML patients, 17 relapsed AML patients) were treated with FLAG regimen.
  • It is concluded that FLAG regimen can be employed in treatment of the refractory or relapsed patients who were not respond to other regimen, and the regiment was safe.

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  • (PMID = 15972128.001).
  • [ISSN] 1009-2137
  • [Journal-full-title] Zhongguo shi yan xue ye xue za zhi
  • [ISO-abbreviation] Zhongguo Shi Yan Xue Ye Xue Za Zhi
  • [Language] CHI
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; FA2DM6879K / Vidarabine
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19. Yamaguchi Y, Usui N, Dobashi N, Yano S, Yahagi Y, Takei Y, Sugiyama K, Ogasawara Y, Saito T, Minami J, Kobayashi T, Katsube A, Kamiyama Y, Machishima T, Morikawa N, Otsubo H, Kaito K, Asai O, Aiba K: Gemtuzumab ozogamicin (GO) in relapsed/refractory patients with acute myeloid leukemia. Gan To Kagaku Ryoho; 2009 Jul;36(7):1105-9
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  • [Title] Gemtuzumab ozogamicin (GO) in relapsed/refractory patients with acute myeloid leukemia.
  • We conducted to evaluate the efficacy and toxicity of GO in our patients with relapsed or refractory AML retrospectively.
  • PATIENTS AND METHODS: Data were collected between March 1, 2000, and March 1, 2006, on 10 patients with relapsed or refractory AML(excluding FAB: M3).
  • CONCLUSION: GO is a valuable new treatment option for relapsed or refractory AML patients, however, the benefit from single agent appears insufficient.
  • [MeSH-major] Aminoglycosides / therapeutic use. Antibodies, Monoclonal / therapeutic use. Antineoplastic Agents / therapeutic use. Leukemia, Myeloid, Acute / drug therapy
  • [MeSH-minor] Adult. Aged. Antibodies, Monoclonal, Humanized. Drug-Induced Liver Injury. Female. Humans. Hypersensitivity / etiology. Male. Middle Aged. Recurrence. Remission Induction. Retrospective Studies. Thrombocytopenia / chemically induced

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  • (PMID = 19620797.001).
  • [ISSN] 0385-0684
  • [Journal-full-title] Gan to kagaku ryoho. Cancer & chemotherapy
  • [ISO-abbreviation] Gan To Kagaku Ryoho
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Aminoglycosides; 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antineoplastic Agents; 0 / gemtuzumab
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20. Sirohi B, Cunningham D, Powles R, Murphy F, Arkenau T, Norman A, Oates J, Wotherspoon A, Horwich A: Long-term outcome of autologous stem-cell transplantation in relapsed or refractory Hodgkin's lymphoma. Ann Oncol; 2008 Jul;19(7):1312-9
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  • [Title] Long-term outcome of autologous stem-cell transplantation in relapsed or refractory Hodgkin's lymphoma.
  • BACKGROUND: The purpose of this study was to assess prognostic factors and outcome of patients with relapsed/refractory Hodgkin's lymphoma (HL) who received high-dose chemotherapy and autologous stem-cell transplant (ASCT).
  • Of 119 patients attaining CR, 27 relapsed: 3 after attaining CR for >5 years and 1 after attaining CR for >10 years.
  • Twenty (10%) patients developed second cancer (seven secondary acute myeloid leukaemia (AML)/myelodysplastic syndrome (MDS)).
  • CONCLUSION: These data provide the longest follow-up reported for patients receiving ASCT for relapsed/refractory HL.

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  • (PMID = 18356139.001).
  • [ISSN] 1569-8041
  • [Journal-full-title] Annals of oncology : official journal of the European Society for Medical Oncology
  • [ISO-abbreviation] Ann. Oncol.
  • [Language] ENG
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 0 / Antineoplastic Agents, Phytogenic; 6PLQ3CP4P3 / Etoposide; Q41OR9510P / Melphalan; U68WG3173Y / Carmustine
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21. Lee SR, Yang DH, Ahn JS, Kim YK, Lee JJ, Choi YJ, Shin HJ, Chung JS, Cho YY, Chae YS, Kim JG, Sohn SK, Kim HJ: The clinical outcome of FLAG chemotherapy without idarubicin in patients with relapsed or refractory acute myeloid leukemia. J Korean Med Sci; 2009 Jun;24(3):498-503
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  • [Title] The clinical outcome of FLAG chemotherapy without idarubicin in patients with relapsed or refractory acute myeloid leukemia.
  • A refractory and resistant disease to conventional induction chemotherapy and relapsed disease are considered as the most important adverse prognostic factors for acute myeloid leukemia (AML).
  • Sixty-one patients (median age, 33.6 yr) with relapsed or refractory AML were treated with the FLAG regimen that consisted of fludarabine (30 mg/m(2), days 1-5), cytarabine (2.0 g/m(2), days 1-5) and granulocyte colony-stimulating factor.
  • There was a significant difference in the response rates according to the duration of leukemia-free survival (pre-LFS) before chemotherapy (P=0.05).
  • In conclusion, FLAG chemotherapy without idarubicin is a relatively effective and well-tolerated regimen for relapsed or refractory AML and the use of FLAG chemotherapy has allowed intensive post-remission therapy including HSCT.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cytarabine / therapeutic use. Granulocyte Colony-Stimulating Factor / therapeutic use. Leukemia, Myeloid, Acute / drug therapy. Vidarabine / analogs & derivatives
  • [MeSH-minor] Adult. Aged. Disease-Free Survival. Female. Humans. Idarubicin / therapeutic use. Male. Middle Aged. Recurrence. Treatment Outcome

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  • (PMID = 19543516.001).
  • [ISSN] 1598-6357
  • [Journal-full-title] Journal of Korean medical science
  • [ISO-abbreviation] J. Korean Med. Sci.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Korea (South)
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine; ZRP63D75JW / Idarubicin
  • [Other-IDs] NLM/ PMC2698199
  • [Keywords] NOTNLM ; FLAG Chemotherapy / Leukemia, Myeloid, Acute / Toxicity
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22. Lasa A, Carricondo M, Estivill C, Bussaglia E, Gich I, Brunet S, Aventin A, Sierra J, Nomdedéu JF: WT1 monitoring in core binding factor AML: comparison with specific chimeric products. Leuk Res; 2009 Dec;33(12):1643-9
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  • [Title] WT1 monitoring in core binding factor AML: comparison with specific chimeric products.
  • Minimal residual disease may help to establish clinical decisions in patients with AML.
  • To compare the value of chimeric specific quantitative PCR with WT1 PCR in CBF acute leukemia, 445 samples from 96 AML (49 AML1-ETO+ and 47 CBFB-MYH11+) cases were included in the study.
  • Concordance was also high in relapsed patients (78% in AML1-ETO and 98% in CBFB-MYH11+ cases).
  • [MeSH-major] Genes, Wilms Tumor. Leukemia, Myeloid, Acute / genetics. Monitoring, Physiologic
  • [MeSH-minor] Adolescent. Adult. Aged. Case-Control Studies. Child. Child, Preschool. Female. Humans. Male. Middle Aged. Mutation. RNA / genetics. Recombinant Fusion Proteins / blood. Young Adult

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  • (PMID = 19427034.001).
  • [ISSN] 1873-5835
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Recombinant Fusion Proteins; 63231-63-0 / RNA
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23. Grandics P: Complete remission achieved in a case of both primary and recurrent adult acute myelogeneous leukemia by a novel nutritional therapy. J Altern Complement Med; 2006 Apr;12(3):311-5
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  • [Title] Complete remission achieved in a case of both primary and recurrent adult acute myelogeneous leukemia by a novel nutritional therapy.
  • OBJECTIVES: The aim of this study was to determine the possible clinical benefit of molasses-based dietary compositions (designated as MSQ 13, MSQ 15, and MSQ 18) in a case of both primary and recurrent adult AML.
  • OUTCOME MEASURES: Clinical improvement and regression of AML were the outcome measures.
  • CONCLUSIONS: Treatment with the MSQ dietary compositions resulted in disease regression and the reversal of clinical manifestations over two episodes of AML.
  • Therefore, further studies are warranted to evaluate the utility of this approach for the clinical management of AML.
  • [MeSH-major] Leukemia, Myeloid, Acute / diet therapy. Molasses. Nutrition Therapy / methods
  • [MeSH-minor] Adult. Female. Humans. Remission Induction. Treatment Outcome

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  • (PMID = 16646731.001).
  • [ISSN] 1075-5535
  • [Journal-full-title] Journal of alternative and complementary medicine (New York, N.Y.)
  • [ISO-abbreviation] J Altern Complement Med
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
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24. Raghavan M, Smith LL, Lillington DM, Chaplin T, Kakkas I, Molloy G, Chelala C, Cazier JB, Cavenagh JD, Fitzgibbon J, Lister TA, Young BD: Segmental uniparental disomy is a commonly acquired genetic event in relapsed acute myeloid leukemia. Blood; 2008 Aug 1;112(3):814-21
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  • [Title] Segmental uniparental disomy is a commonly acquired genetic event in relapsed acute myeloid leukemia.
  • Despite advances in the curative treatment of acute myeloid leukemia (AML), recurrence will occur in the majority of cases.
  • At diagnosis, acquisition of segmental uniparental disomy (UPD) by mitotic recombination has been reported in 15% to 20% of AML cases, associated with homozygous mutations in the region of loss of heterozygosity.
  • DNA from 27 paired diagnostic and relapsed AML samples were analyzed using genotyping arrays.
  • Newly acquired segmental UPDs were observed at relapse in 11 AML samples (40%).
  • Three further AML samples had evidence of acquired segmental UPD of 13q in a subclone of the relapsed leukemia.
  • Finally, a single patient with AML acquired segmental UPD of chromosome 4q, for which the candidate gene is unknown.
  • We conclude that acquisition of segmental UPD and the resulting homozygous mutation is a common event associated with relapse of AML.

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  • (PMID = 18490517.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United Kingdom / Cancer Research UK / / A6438; United Kingdom / Cancer Research UK / / A6789; United Kingdom / Cancer Research UK / /
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / CCAAT-Enhancer-Binding Protein-alpha; EC 2.7.10.1 / fms-Like Tyrosine Kinase 3
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25. Lee JH, Choi SJ, Lee JH, Lee YS, Seol M, Ryu SG, Jang S, Park CJ, Chi HS, Lee JS, Kim WK, Lee KH: Continuous infusion intermediate-dose cytarabine, mitoxantrone, plus etoposide for refractory or early relapsed acute myelogenous leukemia. Leuk Res; 2006 Feb;30(2):204-10
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  • [Title] Continuous infusion intermediate-dose cytarabine, mitoxantrone, plus etoposide for refractory or early relapsed acute myelogenous leukemia.
  • For refractory and early relapsed AML, this prospective phase II clinical trial evaluated a salvage chemotherapy regimen, which was consisted of continuous infusion intermediate-dose cytarabine (1g/m(2)/day, 24h i.v. infusion x 5), mitoxantrone (12 mg/m(2)/day x 3), and etoposide (150 mg/m(2)/day x 3).
  • Our results suggest that continuous infusion intermediate-dose cytarabine, together with mitoxantrone and etoposide, may induce CR in a significant proportion of patients with refractory or early relapsed AML, although remission duration was short.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Leukemia, Myeloid, Acute / drug therapy
  • [MeSH-minor] Adult. Cytarabine / administration & dosage. Etoposide / administration & dosage. Female. Humans. Infusions, Intravenous. Male. Middle Aged. Mitoxantrone / administration & dosage. Prognosis. Prospective Studies. Salvage Therapy

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  • [CommentIn] Leuk Res. 2009 May;33(5):610-2 [18990445.001]
  • (PMID = 16055185.001).
  • [ISSN] 0145-2126
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 6PLQ3CP4P3 / Etoposide; BZ114NVM5P / Mitoxantrone
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26. Chowdhury S, Seropian S, Marks PW: Decitabine combined with fractionated gemtuzumab ozogamicin therapy in patients with relapsed or refractory acute myeloid leukemia. Am J Hematol; 2009 Sep;84(9):599-600
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  • [Title] Decitabine combined with fractionated gemtuzumab ozogamicin therapy in patients with relapsed or refractory acute myeloid leukemia.
  • Salvage chemotherapy for patients with relapsed or refractory acute myeloid leukemia (AML) is generally associated with a low-response rate and significant nonhematologic toxicity.
  • Both decitabine and gemtuzumab ozogamicin have activity in AML as single agents and can be administered sequentially with potential synergy due to their toxicity profiles.
  • Twelve patients with AML, who had received a median of three prior regimens (range 1-6), were treated with decitabine 20 mg/m(2) on days 1 through 5 followed by gemtuzumab ozogamicin 3 mg/m(2) on days 6, 9, and 12.
  • [MeSH-major] Aminoglycosides / administration & dosage. Antibodies, Monoclonal / administration & dosage. Azacitidine / analogs & derivatives. Leukemia, Myeloid, Acute / drug therapy
  • [MeSH-minor] Adult. Aged. Antibodies, Monoclonal, Humanized. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Female. Humans. Male. Middle Aged. Salvage Therapy. Treatment Outcome

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  • (PMID = 19650144.001).
  • [ISSN] 1096-8652
  • [Journal-full-title] American journal of hematology
  • [ISO-abbreviation] Am. J. Hematol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Letter
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Aminoglycosides; 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / gemtuzumab; 776B62CQ27 / decitabine; M801H13NRU / Azacitidine
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27. Hashmi KU, Khan B, Ahmed P, Raza S, Hussain I, Mahmood A, Iqbal H, Malik HS, Anwar M: FLAG-IDA in the treatment of refractory/relapsed acute leukaemias: single centre study. J Pak Med Assoc; 2005 Jun;55(6):234-8
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  • [Title] FLAG-IDA in the treatment of refractory/relapsed acute leukaemias: single centre study.
  • OBJECTIVE: To evaluate the efficacy and toxicity profile of the combination of fludarabine, high dose cytarabine, idarubicin, and granulocyte colony stimulating factor in refractory relapsed cases of acute leukaemia, a study is being conducted at Armed Forces Bone Marrow Transplant Centre (AFBMTC) Rawalpindi since January 2003.
  • METHODS: Twelve Patients with refractory/relapsed (Ref/Rel) acute leukaemia (AL) were treated with fludarabine 30 mg/m2 and cytosine arabinoside (AraC) Arac 2 g/m2 for 5 days, idarubicin 10 mg/m2 for 3 days, and granulocyte colony stimulating factor G-CSF 5 micro g/kg from day 0 till neutrophil recovery (ANC > 1.0 x 10(9)/1).
  • RESULTS: Patients included were refractory acute lymphoblastic leukaemia (ALL) (n=2), relapsed ALL (n = 3), refractory acute myeloid leukaemia (AML) (n = 3), secondary AML (n=2) relapsed AML (n = 1) and acute undifferentiated leukaemia (AUL) (n = 1).
  • Out of 8 patients who achieved CR, 4 underwent allogeneic bone marrow transfusion (BMT), 1 is being evaluated for the same, 1 received idorubicin, AraC and etopuside (ICE) and high dose AraC, 1 did not receive further chemotherapy and 1 relapsed two months after remission.
  • CONCLUSION: In our experience, FLAG-IDA is well tolerated and effective regimen in relapsed/refractory acute leukaemias.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Leukemia, Myeloid / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Vidarabine / analogs & derivatives
  • [MeSH-minor] Acute Disease. Adolescent. Adult. Antibiotics, Antineoplastic / therapeutic use. Antimetabolites, Antineoplastic / therapeutic use. Child. Cytarabine / therapeutic use. Female. Granulocyte Colony-Stimulating Factor / therapeutic use. Humans. Idarubicin / therapeutic use. Male. Middle Aged. Recurrence

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  • (PMID = 16045091.001).
  • [ISSN] 0030-9982
  • [Journal-full-title] JPMA. The Journal of the Pakistan Medical Association
  • [ISO-abbreviation] J Pak Med Assoc
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Pakistan
  • [Chemical-registry-number] 0 / Antibiotics, Antineoplastic; 0 / Antimetabolites, Antineoplastic; 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine; ZRP63D75JW / Idarubicin
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28. Qian SX, Li JY, Wu HX, Zhang R, Hong M, Xu W, Qiu HX: [IDA-FLAG regimen in treatment of patients with refractory or relapsed acute leukemia]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2009 Apr;17(2):464-7
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  • [Title] [IDA-FLAG regimen in treatment of patients with refractory or relapsed acute leukemia].
  • The objective of this study was to evaluate the efficacy and toxicity of the fludarabine combination with high-dose cytarabine (Ara C), idarubicin and granulocyte colony-stimulating factor (G-CSF) (IDA-FLAG regimen) in treatment of refractory/relapsed acute leukemia (AL) patients.
  • 4 patients were male aged from 32 to 44 years, consisted of 3 cases of acute myeloid leukaemia (AML) and 1 cases of acute lymphocytic leukaemia (ALL).
  • The results showed that after one course of induction therapy, 4 patients all achieved complete remission (CR), in which 2 patients were in continuous CR after a follow-up of 3 and 4 months; 1 patient relapsed after 10 months and another one patient died of thrombotic thrombocytopenic purpura at 4 months after allogeneic peripheral blood stem cell transplantation.
  • In conclusion, the IDA-FLAG regimen is effective in treatment of patients with refractory and relapsed AL, the adverse effects from this regimen were well tolerated by patients, which gains time for further treatment.

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  • (PMID = 19379589.001).
  • [ISSN] 1009-2137
  • [Journal-full-title] Zhongguo shi yan xue ye xue za zhi
  • [ISO-abbreviation] Zhongguo Shi Yan Xue Ye Xue Za Zhi
  • [Language] CHI
  • [Publication-type] Clinical Trial; English Abstract; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] China
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine; ZRP63D75JW / Idarubicin
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29. Perea G, Lasa A, Aventín A, Domingo A, Villamor N, Queipo de Llano MP, Llorente A, Juncà J, Palacios C, Fernández C, Gallart M, Font L, Tormo M, Florensa L, Bargay J, Martí JM, Vivancos P, Torres P, Berlanga JJ, Badell I, Brunet S, Sierra J, Nomdedéu JF, Grupo Cooperativo para el Estudio y Tratamiento de las Leucemias Agudas y Miel: Prognostic value of minimal residual disease (MRD) in acute myeloid leukemia (AML) with favorable cytogenetics [t(8;21) and inv(16)]. Leukemia; 2006 Jan;20(1):87-94
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  • [Title] Prognostic value of minimal residual disease (MRD) in acute myeloid leukemia (AML) with favorable cytogenetics [t(8;21) and inv(16)].
  • Most patients with acute myeloid leukemia (AML) and t(8;21) or inv(16) have a good prognosis with current anthracycline- and cytarabine-based protocols.
  • A total of 31% (n=17) of CR patients relapsed: seven with t(8;21) and 10 with inv(16).
  • The mean amount of minimal residual disease (MRD) detected by FC in relapsed and nonrelapsed patients was markedly different: 0.3 vs 0.08% (P=0.002) at the end of treatment.
  • The mean number of fusion transcript copies/ ABL x 10(4) also differed between relapsed and non-relapsed patients: 2385 vs 122 (P=0.001) after induction, 56 vs 7.6 after intensification (P=0.0001) and 75 vs 3.3 (P=0.0001) at the end of chemotherapy.
  • Combined use of FC and RQ-PCR may improve MRD detection, and provide useful clinical information on relapse kinetics in AML patients.
  • [MeSH-major] Chromosomes, Human, Pair 16 / genetics. Chromosomes, Human, Pair 21 / genetics. Chromosomes, Human, Pair 8 / genetics. Leukemia, Myeloid / genetics. Neoplasm, Residual / genetics
  • [MeSH-minor] Acute Disease. Adolescent. Adult. Aged. Child. Child, Preschool. Chromosome Inversion. Cytogenetic Analysis. Female. Flow Cytometry. Follow-Up Studies. Humans. Kinetics. Male. Middle Aged. Prognosis. Recurrence. Reverse Transcriptase Polymerase Chain Reaction. Risk Factors. Survival Rate

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  • (PMID = 16281071.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
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30. Minderman H, O'Loughlin KL, Smith PF, Pendyala L, Greco WR, Sweeney KG, Ford LA, Wetzler M, Baer MR: Sequential administration of irinotecan and cytarabine in the treatment of relapsed and refractory acute myeloid leukemia. Cancer Chemother Pharmacol; 2006 Jan;57(1):73-83
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  • [Title] Sequential administration of irinotecan and cytarabine in the treatment of relapsed and refractory acute myeloid leukemia.
  • PURPOSE: Based on reported synergy of the topoisomerase-I (topo-I) inhibitor irinotecan with antimetabolites, irinotecan and cytarabine (Ara-C) were administered sequentially to patients with acute myeloid leukemia (AML) refractory to or relapsed following high-dose Ara-C and anthracycline therapy.
  • EXPERIMENTAL DESIGN: In vitro synergy of irinotecan followed by Ara-C was confirmed in a human AML cell line as a basis for the clinical trial.
  • This combination is active in refractory AML and warrants further study.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid / drug therapy
  • [MeSH-minor] Acute Disease. Adult. Aged. Camptothecin / administration & dosage. Camptothecin / adverse effects. Camptothecin / analogs & derivatives. Camptothecin / pharmacokinetics. Camptothecin / therapeutic use. Cytarabine / administration & dosage. Cytarabine / adverse effects. Cytarabine / pharmacokinetics. Cytarabine / therapeutic use. DNA Damage. DNA Topoisomerases, Type I / metabolism. DNA, Neoplasm / biosynthesis. Dose-Response Relationship, Drug. Drug Synergism. Female. HL-60 Cells. Humans. Male. Middle Aged. Recurrence

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  • (PMID = 16010591.001).
  • [ISSN] 0344-5704
  • [Journal-full-title] Cancer chemotherapy and pharmacology
  • [ISO-abbreviation] Cancer Chemother. Pharmacol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA 89938; United States / NCI NIH HHS / CA / P30 CA16056
  • [Publication-type] Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / DNA, Neoplasm; 04079A1RDZ / Cytarabine; 7673326042 / irinotecan; EC 5.99.1.2 / DNA Topoisomerases, Type I; XT3Z54Z28A / Camptothecin
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31. Armistead PM, de Lima M, Pierce S, Qiao W, Wang X, Thall PF, Giralt S, Ravandi F, Kantarjian H, Champlin R, Estey E: Quantifying the survival benefit for allogeneic hematopoietic stem cell transplantation in relapsed acute myelogenous leukemia. Biol Blood Marrow Transplant; 2009 Nov;15(11):1431-8
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  • [Title] Quantifying the survival benefit for allogeneic hematopoietic stem cell transplantation in relapsed acute myelogenous leukemia.
  • Allogeneic hematopoietic stem cell transplantation (HSCT) is the recommended therapy for patients with relapsed acute myelogenous leukemia (AML), despite little evidence showing a survival benefit in patients who undergo HSCT versus chemotherapy alone.
  • Because a prospective randomized trial addressing this issue is unlikely, we retrospectively reviewed all patients receiving initial salvage therapy for AML at M.D.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation / statistics & numerical data. Leukemia, Myeloid, Acute / surgery. Salvage Therapy / statistics & numerical data
  • [MeSH-minor] Adult. Aged. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Combined Modality Therapy. Cytarabine / administration & dosage. Humans. Kaplan-Meier Estimate. Middle Aged. Recurrence. Remission Induction. Retrospective Studies. Transplantation Conditioning / methods. Transplantation Conditioning / statistics & numerical data. Transplantation, Homologous / statistics & numerical data. Whole-Body Irradiation / adverse effects. Whole-Body Irradiation / utilization

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  • [Cites] Leukemia. 2000 Mar;14(3):476-9 [10720145.001]
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  • (PMID = 19822303.001).
  • [ISSN] 1523-6536
  • [Journal-full-title] Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • [ISO-abbreviation] Biol. Blood Marrow Transplant.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / P01 CA055164; United States / NCI NIH HHS / CA / P30 CA016672; United States / NCI NIH HHS / CA / T32 CA009666
  • [Publication-type] Comparative Study; Evaluation Studies; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine
  • [Other-IDs] NLM/ NIHMS588413; NLM/ PMC4067765
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32. Styczynski J, Wysocki M, Debski R, Czyzewski K, Kolodziej B, Rafinska B, Kubicka M, Koltan S, Koltan A, Pogorzala M, Kurylak A, Olszewska-Slonina D, Balwierz W, Juraszewska E, Wieczorek M, Olejnik I, Krawczuk-Rybak M, Kuzmicz M, Kowalczyk J, Stefaniak J, Badowska W, Sonta-Jakimczyk D, Szczepanski T, Matysiak M, Malinowska I, Stanczak E, Wachowiak J, Konatkowska B, Gil L, Balcerska A, Maciejka-Kapuscinska L: Predictive value of multidrug resistance proteins and cellular drug resistance in childhood relapsed acute lymphoblastic leukemia. J Cancer Res Clin Oncol; 2007 Nov;133(11):875-93
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  • [Title] Predictive value of multidrug resistance proteins and cellular drug resistance in childhood relapsed acute lymphoblastic leukemia.
  • PURPOSE: Cellular resistance in childhood acute leukemias might be related to profile and function of multidrug resistance proteins and apoptosis regulating proteins.
  • (2) correlation with ex vivo drug resistance, and (3) analysis of their prognostic impact on clinical outcome in childhood acute lymphoblastic (ALL) and acute myeloid (AML) leukemia.
  • METHODS: Total number of 787 children diagnosed for initial ALL (n = 527), relapsed ALL (n = 104), initial AML (n = 133) and relapsed AML (n = 23) were included into the study.
  • RESULTS: Both initial AML and relapsed ALL samples showed higher drug resistance than initial ALL samples.
  • No significant differences were found in drug resistance between initial and relapsed AML samples.
  • CONCLUSIONS: The phenomenon of cellular drug resistance in childhood acute leukemias is multifactorial and plays an important role in response to therapy.
  • Expression of MRP1, PGP and LRP proteins, as well as their co-expression play possible role in childhood relapsed ALL.
  • [MeSH-major] Drug Resistance, Multiple. Drug Resistance, Neoplasm. Multidrug Resistance-Associated Proteins / metabolism. P-Glycoprotein / metabolism. Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism. Vault Ribonucleoprotein Particles / metabolism
  • [MeSH-minor] Adolescent. Adult. Antineoplastic Agents / pharmacology. Child. Child, Preschool. Female. Flow Cytometry. Gene Expression Regulation, Leukemic. Humans. Immunophenotyping. Infant. Infant, Newborn. Male. Neoplasm Recurrence, Local / diagnosis. Prognosis

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  • [ErratumIn] J Cancer Res Clin Oncol. 2007 Nov;133(11):895. Wachowiak, Jacek [added]; Konatkowska, Benigna [added]; Gil, Lidia [added]; Balcerska, Anna [added]; Maciejka-Kapuscinska, Lucyna [added]
  • (PMID = 17671794.001).
  • [ISSN] 0171-5216
  • [Journal-full-title] Journal of cancer research and clinical oncology
  • [ISO-abbreviation] J. Cancer Res. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Multidrug Resistance-Associated Proteins; 0 / P-Glycoprotein; 0 / Vault Ribonucleoprotein Particles; 0 / major vault protein
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33. Hołowiecki J, Grosicki S, Kyrcz-Krzemien S, Skotnicki AB, Piatkowska-Jakubas B, Warzocha K, Seferynska I, Zdziarska B: Daunorubicin, cytarabine and fludarabine (DAF) for remission induction in relapsed or refractory acute myeloid leukemia. Evaluation of safety, tolerance and early outcome--Polish Adult Leukemia Group (PALG) pilot study. Ann Hematol; 2008 May;87(5):361-7
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  • [Title] Daunorubicin, cytarabine and fludarabine (DAF) for remission induction in relapsed or refractory acute myeloid leukemia. Evaluation of safety, tolerance and early outcome--Polish Adult Leukemia Group (PALG) pilot study.
  • Based on these findings and encouraging results of the addition of cladribine to standard daunorubicin+Ara-C induction regimen (DAC) in acute myeloid leukemia (AML), the Polish Adult Leukemia Group (PALG) conducted a pilot study on the administration of cytarabine, daunorubicin, and fludarabine (DAF) as a reinduction treatment of AML to assess tolerance, toxicity, and early outcome.
  • Thirty-four AML patients with median age 39, 24% relapsed and 76% refractory, were included into the study between September 2003 and August 2004.
  • The probability of leukemia-free survival (LFS) for 1 year was 38% (95% CI 22-54%).
  • Summarizing, DAF regimen used as the induction therapy in relapsed/refractory AML was well tolerated with acceptable toxicity and early efficacy.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid, Acute / drug therapy
  • [MeSH-minor] Adult. Cytarabine / administration & dosage. Daunorubicin / administration & dosage. Disease-Free Survival. Female. Humans. Male. Middle Aged. Pilot Projects. Poland. Remission Induction. Vidarabine / administration & dosage. Vidarabine / analogs & derivatives

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  • (PMID = 18074133.001).
  • [ISSN] 0939-5555
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Multicenter Study
  • [Publication-country] Germany
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine; ZS7284E0ZP / Daunorubicin
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34. Denz U, Bertz H, Ihorst G, Wäsch R, Finke J: Improved outcome in relapsed and refractory myeloid malignancies for unrelated vs related donor allogeneic peripheral blood-derived hematopoietic cell transplantation. Bone Marrow Transplant; 2010 Aug;45(8):1309-15
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  • [Title] Improved outcome in relapsed and refractory myeloid malignancies for unrelated vs related donor allogeneic peripheral blood-derived hematopoietic cell transplantation.
  • There are limited data on the comparison of unrelated vs related peripheral blood-derived hematopoietic cell transplantation (HCT) in patients with AML and its implications in high-risk patients.
  • In this single-center retrospective study, we report on a total of 92 consecutive patients with AML (n=87) or myelodysplastic syndrome (MDS; n=5), who were treated between 1996 and 2006 with a uniform preparative regimen of BU and CY and peripheral blood-derived HCT from related (n=46) or unrelated donors (n=46).
  • At transplantation, 45 patients were in CR, 11 were untreated and 36 had relapsed or refractory disease.
  • Unrelated HCT benefited high-risk AML patients with an unfavorable remission status better than related HCT.
  • [MeSH-major] Leukemia, Myeloid, Acute / therapy. Myelodysplastic Syndromes / therapy. Peripheral Blood Stem Cell Transplantation / methods. Salvage Therapy / methods. Tissue Donors
  • [MeSH-minor] Adolescent. Adult. Cyclophosphamide / therapeutic use. Female. Humans. Male. Middle Aged. Remission Induction. Retrospective Studies. Transplantation, Homologous. Treatment Outcome. Young Adult


35. Chevallier P, Hunault-Berger M, Larosa F, Dauriac C, Garand R, Harousseau JL: A phase II trial of high-dose imatinib mesylate for relapsed or refractory c-kit positive and Bcr-Abl negative acute myeloid leukaemia: the AFR-15 trial. Leuk Res; 2009 Aug;33(8):1124-6
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  • [Title] A phase II trial of high-dose imatinib mesylate for relapsed or refractory c-kit positive and Bcr-Abl negative acute myeloid leukaemia: the AFR-15 trial.
  • This was a phase II investigation of high-dose imatinib in 15 adult patients with relapsed or refractory c-kit positive and Bcr-Abl negative acute myeloid leukaemia (AML).
  • While no activity was seen in this phase II trial, the findings of the study do not rule out efficacy in subsets of AML with imatinib-sensitive Kit mutations.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Genes, abl. Leukemia, Myeloid, Acute / drug therapy. Piperazines / administration & dosage. Proto-Oncogene Proteins c-kit. Pyrimidines / administration & dosage
  • [MeSH-minor] Adult. Aged. Benzamides. Disease-Free Survival. Female. Humans. Imatinib Mesylate. Male. Middle Aged. Survival Rate. Time Factors

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  • (PMID = 18990444.001).
  • [ISSN] 1873-5835
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Proto-Oncogene Proteins c-kit
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36. Sung WJ, Kim DH, Sohn SK, Kim JG, Baek JH, Jeon SB, Moon JH, Ahn BM, Lee KB: Phase II trial of amsacrine plus intermediate-dose Ara-C (IDAC) with or without etoposide as salvage therapy for refractory or relapsed acute leukemia. Jpn J Clin Oncol; 2005 Oct;35(10):612-6
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  • [Title] Phase II trial of amsacrine plus intermediate-dose Ara-C (IDAC) with or without etoposide as salvage therapy for refractory or relapsed acute leukemia.
  • OBJECTIVE: The current trial attempted to evaluate the efficacy and toxicity of a salvage therapy consisting of amsacrine plus intermediate-dose Ara-C (IDAC) with or without etoposide for acute leukemia patients in refractory or relapsed states.
  • METHODS: A total of 51 patients with refractory or relapsed acute leukemia were included in the current trial.
  • Twenty-nine patients with acute myeloid leukemia (AML) received a salvage therapy of amsacrine plus IDAC and etoposide, while 22 patients with acute lymphoblastic leukemia (ALL) received amsacrine plus IDAC.
  • RESULTS: The overall complete remission rate was 55% (45% for AML, 68% for ALL) and the median duration of overall survival was 144 days (95% confidence interval = 101-186 days).
  • CONCLUSION: A salvage therapy consisting of amsacrine plus IDAC with or without etoposide appears to be safe and an effective bridge therapy into a stem cell transplantation programme for patients with refractory or relapsed acute leukemia.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid, Acute / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Salvage Therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Amsacrine / administration & dosage. Cytarabine / administration & dosage. Diarrhea / chemically induced. Drug Administration Schedule. Etoposide / administration & dosage. Female. Humans. Male. Middle Aged. Nausea / chemically induced. Remission Induction. Survival Rate. Treatment Outcome. Vomiting, Anticipatory / etiology

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  • (PMID = 16172175.001).
  • [ISSN] 0368-2811
  • [Journal-full-title] Japanese journal of clinical oncology
  • [ISO-abbreviation] Jpn. J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 00DPD30SOY / Amsacrine; 04079A1RDZ / Cytarabine; 6PLQ3CP4P3 / Etoposide
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37. Zhu BG, Qian SX, Hong M, Lu H, Wu HX, Zhang SJ, Qiu HX, Xu W, Li JY: [Low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor priming in 50 patients with relapsed acute myeloid leukemia]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2009 Jun;17(3):760-4
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  • [Title] [Low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor priming in 50 patients with relapsed acute myeloid leukemia].
  • To evaluate the efficacy and toxicity of low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (G-CSF) protocol for patients with relapsed acute myeloid leukemia (AML).
  • A total of fifty relapsed patients have been enrolled, including 13 early relapsed and 37 late relapsed.
  • Out of them, 7 patients relapsed after allogeneic peripheral blood stem cell transplantation (allo-PBSCT), 3 patients relapsed after autologous peripheral blood stem cell transplantation (auto-PBSCT), 25 patients relapsed after received regimens including high dose cytarabine and 15 patients relapsed after CR or stopping chemical therapy themself in course of consolidatory therapy.
  • 30 relapsed patients received CAG regimen, and 20 patients (control group) received an anthracycline in combination with cytarabine.
  • In conclusion, CAG regimen as the induction therapy is effective and well tolerable with low side effects for relapsed patients who had received high dose cytarabine, auto-PBSCT or allo-PBSCT.

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  • (PMID = 19549403.001).
  • [ISSN] 1009-2137
  • [Journal-full-title] Zhongguo shi yan xue ye xue za zhi
  • [ISO-abbreviation] Zhongguo Shi Yan Xue Ye Xue Za Zhi
  • [Language] CHI
  • [Publication-type] Controlled Clinical Trial; English Abstract; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] China
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 74KXF8I502 / Aclarubicin
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38. Li QH, DU X, Huang ZL, Luo CW, Zhong LY, Lin W: [Therapeutic effects of chemotherapeutic regimens containing pirarubicin on the treatment of high-risk or refractory and relapsed acute leukemia in adults]. Zhonghua Yi Xue Za Zhi; 2005 May 11;85(17):1195-7
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  • [Title] [Therapeutic effects of chemotherapeutic regimens containing pirarubicin on the treatment of high-risk or refractory and relapsed acute leukemia in adults].
  • OBJECTIVE: To evaluate the therapeutic effects of chemotherapeutic regimen containing pirarubicin (THP) on the treatment of high-risk or refractory and relapsed acute leukemia (AL) in adults.
  • METHODS: Forty patients with high-risk or refractory and relapsed AL, 26 males and 14 females, aged 33 (14-63) received treatment regimens with THP: TA regimen [THP + cytosine-arabinoside (Ara-C)] for acute myeloid leukemia (AML) and TAOP regimen [THP + Ara-C + vincristine (VCR) + prednisone (Pred)] for acute lymphocytic leukemia (ALL) or biphenotype-AL.
  • Forty matched patients received mitoxantron (MIT) + Ara-C for AML or MIT + Ara-C + VCR + Pred for ALL and biphenotype AL as controls.
  • CONCLUSION: Regimens with THP are more effective on treatment of high-risk or refractory and relapsed AL in adults, however, with more serious marrow suppression and higher incidence of infection.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Doxorubicin / analogs & derivatives. Leukemia, Myeloid, Acute / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • [MeSH-minor] Adolescent. Adult. Cytarabine / administration & dosage. Female. Humans. Male. Middle Aged. Recurrence. Vincristine / administration & dosage

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  • (PMID = 16029595.001).
  • [ISSN] 0376-2491
  • [Journal-full-title] Zhonghua yi xue za zhi
  • [ISO-abbreviation] Zhonghua Yi Xue Za Zhi
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] China
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 5J49Q6B70F / Vincristine; 80168379AG / Doxorubicin; D58G680W0G / pirarubicin
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39. Zhang WG, Wang FX, Chen YX, Cao XM, He AL, Liu J, Ma XR, Zhao WH, Liu SH, Wang JL: Combination chemotherapy with low-dose cytarabine, homoharringtonine, and granulocyte colony-stimulating factor priming in patients with relapsed or refractory acute myeloid leukemia. Am J Hematol; 2008 Mar;83(3):185-8
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  • [Title] Combination chemotherapy with low-dose cytarabine, homoharringtonine, and granulocyte colony-stimulating factor priming in patients with relapsed or refractory acute myeloid leukemia.
  • As sensitization of leukemic cells with granulocyte colony-stimulating factor (G-csf) can enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML), a pilot study was conducted in order to evaluate the effect of G-csf priming combined with low-dose chemotherapy in patients with relapsed and refractory AML.
  • Thirty-six AML patients were enrolled, 23 refractory and 13 relapsed.
  • The G-HA regimen is effective in remission induction for refractory and relapsed AML patients and well tolerated in maintenance therapy in some subgroups of elderly patients.
  • Further studies are necessary to elucidate optimum dose and schedule for this regimen to enhance the treatment efficacy of relapsed or refractory AML patients.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid, Acute / drug therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Clinical Trials, Phase I as Topic. Cytarabine / administration & dosage. Female. Granulocyte Colony-Stimulating Factor / administration & dosage. Harringtonines / administration & dosage. Humans. Male. Middle Aged. Neutropenia / chemically induced. Retrospective Studies. Treatment Outcome

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  • [Copyright] (c) 2007 Wiley-Liss, Inc.
  • (PMID = 17899614.001).
  • [ISSN] 0361-8609
  • [Journal-full-title] American journal of hematology
  • [ISO-abbreviation] Am. J. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Harringtonines; 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 6FG8041S5B / homoharringtonine
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40. Lee SS, Lee JH, Lee JH, Kim DY, Kim SH, Lim SN, Lee YS, Seol M, Ryu SG, Kang YA, Jang S, Park CJ, Chi HS, Yun SC, Lee KH: Single-dose mitoxantrone in combination with continuous infusion intermediate-dose cytarabine plus etoposide for treatment of refractory or early relapsed acute myeloid leukemia. Leuk Res; 2009 Apr;33(4):511-7
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  • [Title] Single-dose mitoxantrone in combination with continuous infusion intermediate-dose cytarabine plus etoposide for treatment of refractory or early relapsed acute myeloid leukemia.
  • This prospective phase II clinical trial evaluated the effects of single-dose mitoxantrone (36 mg/m2 on day 1) in combination with continuous infusion intermediate-dose cytarabine plus etoposide in 25 patients with refractory or early relapsed acute myeloid leukemia (AML).
  • In conclusion, single-dose mitoxantrone was inferior to conventional divided-dose mitoxantrone for treatment of refractory or early relapsed AML in terms of CR rate.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid, Acute / drug therapy. Neoplasm Recurrence, Local / drug therapy. Salvage Therapy / methods
  • [MeSH-minor] Adult. Cytarabine / administration & dosage. Cytarabine / adverse effects. Etoposide / administration & dosage. Etoposide / adverse effects. Female. Humans. Kaplan-Meier Estimate. Male. Middle Aged. Mitoxantrone / administration & dosage. Mitoxantrone / adverse effects. Treatment Outcome

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  • (PMID = 18819710.001).
  • [ISSN] 1873-5835
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 6PLQ3CP4P3 / Etoposide; BZ114NVM5P / Mitoxantrone
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41. Yao YY, Zhu Q, Zou LF, Dou HJ, Chen YM, Tang Y, Hu JP: [Clinical study on fludarabine combined with cytarabine regimen in the treatment of patients with refractory and relapsed acute myeloid leukemia]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2009 Jun;17(3):774-6
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  • [Title] [Clinical study on fludarabine combined with cytarabine regimen in the treatment of patients with refractory and relapsed acute myeloid leukemia].
  • The aim of study was to evaluate the clinical efficacy and toxicity of fludarabine combined with cytarabine (FA) regimen in the treatment of patients with refractory and/or relapsed acute myeloid leukemia (AML).
  • Nineteen cases with refractory/relapsed AML were treated with FA regimen in which fludarabine phosphate 25 mg/(m(2) x d), d1-5; cytarabine (Ara-C) 2 g/(m(2) x d), d1-5.
  • In conclusion, FA regimen is an effective regimen for treatment of refractory and relapsed AML.

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  • (PMID = 19549406.001).
  • [ISSN] 1009-2137
  • [Journal-full-title] Zhongguo shi yan xue ye xue za zhi
  • [ISO-abbreviation] Zhongguo Shi Yan Xue Ye Xue Za Zhi
  • [Language] CHI
  • [Publication-type] Clinical Trial; English Abstract; Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine
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42. Yamada K, Mizusawa M, Harima A, Kajiwara K, Hamaki T, Hoshi K, Kozai Y, Kodo H: Induction of remission of relapsed acute myeloid leukemia after unrelated donor cord blood transplantation by concomitant low-dose cytarabine and calcitriol in adults. Eur J Haematol; 2006 Oct;77(4):345-8
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  • [Title] Induction of remission of relapsed acute myeloid leukemia after unrelated donor cord blood transplantation by concomitant low-dose cytarabine and calcitriol in adults.
  • Low-dose cytarabine and calcitriol (LDCA + VD3) combination therapy was performed in two adult patients with acute myeloid leukemia (AML) that relapsed within 1 yr after unrelated donor cord blood transplantation (URD CBT) performed in a relapse or non-remission stage.
  • Although LDCA + VD3 therapy is minimally intensive chemotherapy, it may prolong the survival time of patients with relapsed AML after URD CBT.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cord Blood Stem Cell Transplantation. Leukemia, Myeloid / surgery. Remission Induction
  • [MeSH-minor] Aclarubicin / administration & dosage. Acute Disease. Calcitriol / administration & dosage. Cytarabine / administration & dosage. Dose-Response Relationship, Drug. Female. Humans. Middle Aged. Recurrence. Reverse Transcriptase Polymerase Chain Reaction

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  • (PMID = 16930144.001).
  • [ISSN] 0902-4441
  • [Journal-full-title] European journal of haematology
  • [ISO-abbreviation] Eur. J. Haematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Denmark
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 74KXF8I502 / Aclarubicin; FXC9231JVH / Calcitriol
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43. Shih LY, Liang DC, Huang CF, Wu JH, Lin TL, Wang PN, Dunn P, Kuo MC, Tang TC: AML patients with CEBPalpha mutations mostly retain identical mutant patterns but frequently change in allelic distribution at relapse: a comparative analysis on paired diagnosis and relapse samples. Leukemia; 2006 Apr;20(4):604-9
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  • [Title] AML patients with CEBPalpha mutations mostly retain identical mutant patterns but frequently change in allelic distribution at relapse: a comparative analysis on paired diagnosis and relapse samples.
  • The roles of CEBPalpha mutations and its cooperating mutations in the relapse of acute myeloid leukemia (AML) are not clear.
  • CEBPalpha mutations were analyzed on 149 patients with de novo AML at both diagnosis and relapse.
  • Twenty patients relapsed with identical mutant patterns, two lost CEBPalpha mutations and none acquired the mutations at relapse.
  • Our study showed that 91% of de novo AML harboring CEBPalpha mutations at diagnosis retained the identical mutant patterns but frequently changed in the allelic distribution at relapse.
  • [MeSH-major] CCAAT-Enhancer-Binding Protein-alpha / genetics. Leukemia, Myeloid, Acute / diagnosis. Leukemia, Myeloid, Acute / genetics. Mutation
  • [MeSH-minor] Adolescent. Adult. Aged. Alleles. Bone Marrow / pathology. Child. Child, Preschool. DNA Mutational Analysis. Disease Progression. Female. Genes, ras / genetics. Humans. Infant. Male. Middle Aged. Recurrence. fms-Like Tyrosine Kinase 3 / genetics

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  • (PMID = 16453003.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / CCAAT-Enhancer-Binding Protein-alpha; EC 2.7.10.1 / FLT3 protein, human; EC 2.7.10.1 / fms-Like Tyrosine Kinase 3
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44. Sampath D, Cortes J, Estrov Z, Du M, Shi Z, Andreeff M, Gandhi V, Plunkett W: Pharmacodynamics of cytarabine alone and in combination with 7-hydroxystaurosporine (UCN-01) in AML blasts in vitro and during a clinical trial. Blood; 2006 Mar 15;107(6):2517-24
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  • [Title] Pharmacodynamics of cytarabine alone and in combination with 7-hydroxystaurosporine (UCN-01) in AML blasts in vitro and during a clinical trial.
  • Similarly, primary acute myelogenous leukemia (AML) blasts exposed to ara-C and UCN-01 demonstrated a selective loss in cloning potential when compared with normal progenitors.
  • Therefore, we evaluated a pilot clinical trial of ara-C in combination with UCN-01 in patients with relapsed AML.
  • Constitutively phosphorylated Akt kinase declined on addition of UCN-01 to the ara-C infusion, an action accompanied by an activation of JNK and reduction in absolute AML blast counts.
  • Thus, use of UCN-01 in combination with ara-C decreases Chk1 phosphorylation, inhibits the Akt survival pathway, and activates JNK during the course of therapy, offering a rationale for the cytotoxic action of this combination during AML treatment.

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  • (PMID = 16293603.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / P30 CA016672; United States / NCI NIH HHS / CA / CA62461; United States / NCI NIH HHS / CA / CA55164; United States / NCI NIH HHS / CA / CA32839; United States / NCI NIH HHS / CA / P50 CA16672; United States / NCI NIH HHS / CA / CA28596
  • [Publication-type] Clinical Trial; Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 7BU5H4V94A / 7-hydroxystaurosporine; EC 2.7.- / Protein Kinases; EC 2.7.11.1 / Checkpoint kinase 1; EC 2.7.11.1 / Oncogene Protein v-akt; EC 2.7.11.22 / CDK2 protein, human; EC 2.7.11.22 / Cyclin-Dependent Kinase 2; EC 2.7.11.24 / JNK Mitogen-Activated Protein Kinases; H88EPA0A3N / Staurosporine
  • [Other-IDs] NLM/ PMC1895741
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45. Hosing C, Saliba RM, Shahjahan M, Estey EH, Couriel D, Giralt S, Andersson B, Champlin RE, De Lima M: Disease burden may identify patients more likely to benefit from second allogeneic hematopoietic stem cell transplantation to treat relapsed acute myelogenous leukemia. Bone Marrow Transplant; 2005 Jul;36(2):157-62
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  • [Title] Disease burden may identify patients more likely to benefit from second allogeneic hematopoietic stem cell transplantation to treat relapsed acute myelogenous leukemia.
  • The major cause of failure after allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) is disease relapse or progression.
  • We analyzed the outcome of second HSCT for treatment of patients with relapsed, refractory AML/myelodysplastic syndrome (MDS) at our institution.
  • A total of 20 patients (28%) had low leukemia burden as measured by the absence of peripheral blood blasts and <or=5% blasts in the bone marrow at the time of the second transplant.
  • Although, the overall median survival after the second transplant was 6 months, a subset of patients who had low leukemia burden at the time of the second transplant had a 5-year survival of 25 vs 12% in those with a high leukemia burden.
  • [MeSH-major] Leukemia, Myeloid, Acute / prevention & control. Salvage Therapy. Stem Cell Transplantation. Tumor Burden
  • [MeSH-minor] Adolescent. Adult. Aged. Bone Marrow / pathology. Disease-Free Survival. Female. Humans. Male. Middle Aged. Recurrence. Retrospective Studies


46. Metzelder SK, Wollmer E, Neubauer A, Burchert A: [Sorafenib in relapsed and refractory FLT3-ITD positive acute myeloid leukemia: a novel treatment option]. Dtsch Med Wochenschr; 2010 Sep;135(38):1852-6
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  • [Title] [Sorafenib in relapsed and refractory FLT3-ITD positive acute myeloid leukemia: a novel treatment option].
  • BACKGROUND: The therapeutic options for relapsed or refractory FLT3-ITD positive AML are limited, particularly in case of a prior allogenic stem cell transplantation (SCT) or poor performance status.
  • PATIENTS AND METHODS: Between 2007 and 2010 eight patients (4 men, 4 women; age 40-75 years) with relapsed or refractory FLT3-ITD positive acute myeloid leukemia (AML) before (n=4) and after allogenic SCT (n=5) were treated off-label with sorafenib.
  • CONCLUSION: Sorafenib is apparently an effective treatment alternative for patients with relapsed or refractory FLT3-ITD positive AML.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Benzenesulfonates / therapeutic use. DNA Mutational Analysis. Leukemia, Myeloid, Acute / drug therapy. Leukemia, Myeloid, Acute / genetics. Off-Label Use. Pyridines / therapeutic use
  • [MeSH-minor] Adult. Aged. Combined Modality Therapy. Dose-Response Relationship, Drug. Female. Hematopoietic Stem Cell Transplantation. Humans. Male. Middle Aged. Niacinamide / analogs & derivatives. Phenylurea Compounds. Remission Induction. Retreatment

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  • [Copyright] © Georg Thieme Verlag KG Stuttgart · New York.
  • (PMID = 20740398.001).
  • [ISSN] 1439-4413
  • [Journal-full-title] Deutsche medizinische Wochenschrift (1946)
  • [ISO-abbreviation] Dtsch. Med. Wochenschr.
  • [Language] ger
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzenesulfonates; 0 / Phenylurea Compounds; 0 / Pyridines; 25X51I8RD4 / Niacinamide; 9ZOQ3TZI87 / sorafenib
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47. Owonikoko T, Agha M, Balassanian R, Smith R, Raptis A: Gemtuzumab therapy for isolated extramedullary AML relapse following allogeneic stem-cell transplant. Nat Clin Pract Oncol; 2007 Aug;4(8):491-5
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  • [Title] Gemtuzumab therapy for isolated extramedullary AML relapse following allogeneic stem-cell transplant.
  • BACKGROUND: A 19-year-old male with primary refractory acute myeloid leukemia received salvage therapy with mitoxantrone and cytarabine combination.
  • The disease relapsed in the bone marrow (BM) 9 months after the initial stem-cell transplant, and was successfully treated by repeat transplant from the same donor.
  • DIAGNOSIS: Isolated extramedullary relapse of acute myeloid leukemia after stem-cell transplant.
  • MANAGEMENT: Primary leukemia treatment with idarubicin, cytarabine, etoposide, dexamethasone, tioguanine on protocol and salvage therapy with mitoxantrone and cytarabine combination for primary refractory disease.
  • A matched-unrelated-donor stem-cell transplant for consolidation and donor-lymphocyte infusions were performed, followed by repeat unrelated-donor transplant for leukemia relapse in the marrow, radiation therapy and gemtuzumab ozogamicin for multiple sites of extramedullary leukemia relapse.
  • [MeSH-major] Aminoglycosides / therapeutic use. Antibodies, Monoclonal / therapeutic use. Antineoplastic Agents / therapeutic use. Hematopoietic Stem Cell Transplantation / adverse effects. Neoplasm Recurrence, Local / drug therapy. Sarcoma, Myeloid / drug therapy
  • [MeSH-minor] Adult. Antibodies, Monoclonal, Humanized. Humans. Male

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  • (PMID = 17657254.001).
  • [ISSN] 1743-4262
  • [Journal-full-title] Nature clinical practice. Oncology
  • [ISO-abbreviation] Nat Clin Pract Oncol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Aminoglycosides; 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antineoplastic Agents; 0 / gemtuzumab
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48. Weisser M, Haferlach C, Haferlach T, Schnittger S: Advanced age and high initial WBC influence the outcome of inv(3) (q21q26)/t(3;3) (q21;q26) positive AML. Leuk Lymphoma; 2007 Nov;48(11):2145-51
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  • [Title] Advanced age and high initial WBC influence the outcome of inv(3) (q21q26)/t(3;3) (q21;q26) positive AML.
  • AML with inv(3)/t(3;3) are generally considered of having a poor prognosis.
  • For further insight in this rare entity the outcome of 65 inv(3)/t(3;3) positive AML cases were examined with special emphasis o n patient a nd disease related factors at diagnosis.
  • Eight patients (50%) relapsed.
  • Our data (1) confirm that inv(3)/t(3;3) AML has a poor prognosis (2) show that age and initial WBC are risk factors for prognosis;.
  • [MeSH-major] Aged. Chromosome Inversion. Chromosomes, Human, Pair 3. Leukemia, Myeloid, Acute / diagnosis. Leukemia, Myeloid, Acute / genetics. Leukocyte Count. Translocation, Genetic
  • [MeSH-minor] Adult. Age Factors. Aged, 80 and over. Aminoglutethimide / therapeutic use. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cohort Studies. Cytarabine / therapeutic use. Danazol / therapeutic use. Female. Follow-Up Studies. Hematopoietic Stem Cell Transplantation. Humans. Karyotyping. Male. Middle Aged. Mitoxantrone / therapeutic use. Prognosis. Survival Analysis. Tamoxifen / therapeutic use

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  • [CommentIn] Leuk Lymphoma. 2007 Nov;48(11):2096-7 [17990175.001]
  • (PMID = 17926191.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Evaluation Studies; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 094ZI81Y45 / Tamoxifen; 0O54ZQ14I9 / Aminoglutethimide; BZ114NVM5P / Mitoxantrone; N29QWW3BUO / Danazol; MAC chemotherapy protocol; TAD protocol
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49. Gorman MF, Ji L, Ko RH, Barnette P, Bostrom B, Hutchinson R, Raetz E, Seibel NL, Twist CJ, Eckroth E, Sposto R, Gaynon PS, Loh ML: Outcome for children treated for relapsed or refractory acute myelogenous leukemia (rAML): a Therapeutic Advances in Childhood Leukemia (TACL) Consortium study. Pediatr Blood Cancer; 2010 Sep;55(3):421-9
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  • [Title] Outcome for children treated for relapsed or refractory acute myelogenous leukemia (rAML): a Therapeutic Advances in Childhood Leukemia (TACL) Consortium study.
  • BACKGROUND: Current event-free survival (EFS) rates for children with newly diagnosed acute myeloid leukemia (AML) approach 50-60%.
  • This report highlights efforts to assess the response rates and survival outcomes after first or greater relapse in children with AML.
  • PROCEDURE: We performed a retrospective cohort review of pediatric patients with relapsed and refractory AML (rAML) previously treated at TACL institutions between the years of 1995 and 2004.
  • [MeSH-major] Leukemia, Myeloid, Acute / drug therapy
  • [MeSH-minor] Adolescent. Child. Child, Preschool. Disease-Free Survival. Female. Humans. Infant. Male. Prognosis. Recurrence. Remission Induction. Retreatment. Survival Rate. Treatment Outcome. Young Adult

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  • [Copyright] 2010 Wiley-Liss, Inc.
  • (PMID = 20658611.001).
  • [ISSN] 1545-5017
  • [Journal-full-title] Pediatric blood & cancer
  • [ISO-abbreviation] Pediatr Blood Cancer
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / K22 CA113557
  • [Publication-type] Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
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50. Kobayashi Y, Tobinai K, Takeshita A, Naito K, Asai O, Dobashi N, Furusawa S, Saito K, Mitani K, Morishima Y, Ogura M, Yoshiba F, Hotta T, Bessho M, Matsuda S, Takeuchi J, Miyawaki S, Naoe T, Usui N, Ohno R: Phase I/II study of humanized anti-CD33 antibody conjugated with calicheamicin, gemtuzumab ozogamicin, in relapsed or refractory acute myeloid leukemia: final results of Japanese multicenter cooperative study. Int J Hematol; 2009 May;89(4):460-9
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  • [Title] Phase I/II study of humanized anti-CD33 antibody conjugated with calicheamicin, gemtuzumab ozogamicin, in relapsed or refractory acute myeloid leukemia: final results of Japanese multicenter cooperative study.
  • The primary objective of this study was to investigate the tolerability, efficacy and pharmacokinetic profile of gemtuzumab ozogamicin (GO) in patients with relapsed and/or refractory CD33-positive acute myeloid leukemia (AML).
  • The pharmacokinetic study revealed that Cmax and AUC were equivalent to those of non-Japanese patients.
  • GO is safe and effective as a single agent among Japanese CD33-positive AML patients.
  • Remission lasted longer in a subset of patients than in non-Japanese patients in earlier studies.
  • [MeSH-major] Aminoglycosides / therapeutic use. Antibodies, Monoclonal / therapeutic use. Antigens, CD / immunology. Antigens, Differentiation, Myelomonocytic / immunology. Antineoplastic Agents / therapeutic use. Biomarkers, Tumor / immunology. Leukemia, Myeloid, Acute / drug therapy
  • [MeSH-minor] Adult. Aged. Antibodies, Monoclonal, Humanized. Dose-Response Relationship, Drug. Female. Humans. Japan. Male. Middle Aged. Recurrence. Sialic Acid Binding Ig-like Lectin 3

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  • (PMID = 19360457.001).
  • [ISSN] 1865-3774
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Aminoglycosides; 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antigens, CD; 0 / Antigens, Differentiation, Myelomonocytic; 0 / Antineoplastic Agents; 0 / Biomarkers, Tumor; 0 / CD33 protein, human; 0 / Sialic Acid Binding Ig-like Lectin 3; 0 / gemtuzumab
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51. Jeha S, Razzouk B, Rytting M, Rheingold S, Albano E, Kadota R, Luchtman-Jones L, Bomgaars L, Gaynon P, Goldman S, Ritchey K, Arceci R, Altman A, Stine K, Steinherz L, Steinherz P: Phase II study of clofarabine in pediatric patients with refractory or relapsed acute myeloid leukemia. J Clin Oncol; 2009 Sep 10;27(26):4392-7
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  • [Title] Phase II study of clofarabine in pediatric patients with refractory or relapsed acute myeloid leukemia.
  • PURPOSE: To determine the efficacy and safety of clofarabine in pediatric patients with refractory or relapsed acute myeloid leukemia (AML).
  • PATIENTS AND METHODS: A phase II, open-label, multicenter study was conducted with single-agent clofarabine in pediatric patients with refractory or relapsed AML.
  • CONCLUSION: Clofarabine is active in pediatric patients with multiply relapsed or refractory AML.
  • [MeSH-major] Adenine Nucleotides / therapeutic use. Arabinonucleosides / therapeutic use. Leukemia, Myeloid / drug therapy
  • [MeSH-minor] Acute Disease. Adolescent. Antineoplastic Agents / adverse effects. Antineoplastic Agents / therapeutic use. Child. Child, Preschool. Drug Resistance, Neoplasm. Female. Fever / etiology. Hematopoietic Stem Cell Transplantation / adverse effects. Hematopoietic Stem Cell Transplantation / methods. Humans. Male. Nausea / etiology. Neutropenia / etiology. Recurrence. Remission Induction. Treatment Outcome. Young Adult

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  • (PMID = 19652076.001).
  • [ISSN] 1527-7755
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / P30 CA021765; United States / NCI NIH HHS / CA / CA21765
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Adenine Nucleotides; 0 / Antineoplastic Agents; 0 / Arabinonucleosides; 762RDY0Y2H / clofarabine
  • [Other-IDs] NLM/ PMC2744276
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52. Hijiya N, Gaynon P, Barry E, Silverman L, Thomson B, Chu R, Cooper T, Kadota R, Rytting M, Steinherz P, Shen V, Jeha S, Abichandani R, Carroll WL: A multi-center phase I study of clofarabine, etoposide and cyclophosphamide in combination in pediatric patients with refractory or relapsed acute leukemia. Leukemia; 2009 Dec;23(12):2259-64
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  • [Title] A multi-center phase I study of clofarabine, etoposide and cyclophosphamide in combination in pediatric patients with refractory or relapsed acute leukemia.
  • This Phase I study of clofarabine with etoposide and cyclophosphamide for children with relapsed/refractory acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) was conducted to determine the maximum tolerated dose (MTD), dose-limiting toxicities and the recommended phase 2 doses (RP2Ds).
  • A total of 25 patients (20 ALL and 5 AML) were enrolled in five cohorts.
  • Complete remission (CR) was achieved in 10 patients (ALL: nine; AML: one), and CR without platelet recovery in six patients (ALL: two; AML: four) for an overall response rate of 64% (ALL: 55%; AML: 100%).
  • In conclusion, the combination of clofarabine, etoposide and cyclophosphamide was well tolerated and effective in pediatric patients with relapsed/refractory leukemia.
  • [MeSH-major] Adenine Nucleotides / administration & dosage. Arabinonucleosides / administration & dosage. Cyclophosphamide / administration & dosage. Etoposide / administration & dosage. Leukemia / drug therapy. Salvage Therapy / methods
  • [MeSH-minor] Acute Disease. Adolescent. Antineoplastic Combined Chemotherapy Protocols / adverse effects. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Antineoplastic Combined Chemotherapy Protocols / toxicity. Child. Child, Preschool. Drug-Induced Liver Injury. Hematopoietic Stem Cell Transplantation. Humans. Infant. Leukemia, Myeloid, Acute / complications. Leukemia, Myeloid, Acute / drug therapy. Maximum Tolerated Dose. Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Remission Induction. Treatment Outcome. Young Adult

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  • (PMID = 19741725.001).
  • [ISSN] 1476-5551
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Adenine Nucleotides; 0 / Arabinonucleosides; 6PLQ3CP4P3 / Etoposide; 762RDY0Y2H / clofarabine; 8N3DW7272P / Cyclophosphamide
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53. Yamauchi T, Mori Y, Miyamoto T, Kamezaki K, Aoki T, Yamamoto A, Takenaka K, Iwasaki H, Harada N, Nagafuji K, Teshima T, Akashi K: Second unrelated cord blood transplantation using a reduced-intensity conditioning regimen combined with gemtuzumab ozogamicin in patients with relapsed acute myelogenous leukemia. Int J Hematol; 2009 Oct;90(3):416-20
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  • [Title] Second unrelated cord blood transplantation using a reduced-intensity conditioning regimen combined with gemtuzumab ozogamicin in patients with relapsed acute myelogenous leukemia.
  • Gemtuzumab ozogamicin (GO) is an effective molecular-targeted agent for CD33-positive acute myelogenous leukemia (AML) patients who are resistant to conventional chemotherapy.
  • We report here for the first time three AML cases that relapsed after allogeneic SCT and underwent unrelated cord blood transplantation (UCBT) following reduced-intensity conditioning (RIC) comprising fludarabine, melphalan, and low-dose total body irradiation combined with GO.
  • Non-relapse mortality at day 100 was not documented.
  • Notably, one patient who responded to GO survived for 6 months after UCBT in remission with excellent performance status, while the remaining cases relapsed early.
  • [MeSH-major] Aminoglycosides / therapeutic use. Antibodies, Monoclonal / therapeutic use. Antineoplastic Agents / therapeutic use. Cord Blood Stem Cell Transplantation. Leukemia, Myeloid, Acute / drug therapy. Transplantation Conditioning / methods
  • [MeSH-minor] Adult. Antibodies, Monoclonal, Humanized. Combined Modality Therapy. Fatal Outcome. Female. Humans. Male. Middle Aged. Recurrence

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  • (PMID = 19697098.001).
  • [ISSN] 1865-3774
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Aminoglycosides; 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antineoplastic Agents; 0 / gemtuzumab
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54. Kalaycio M, Rybicki L, Pohlman B, Sobecks R, Ball E, Cook D, Andresen S, Kuczkowski E, Bolwell B: CD8+ T-cell-depleted, matched unrelated donor, allogeneic bone marrow transplantation for advanced AML using busulfan-based preparative regimens. Bone Marrow Transplant; 2005 Feb;35(3):247-52
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  • [Title] CD8+ T-cell-depleted, matched unrelated donor, allogeneic bone marrow transplantation for advanced AML using busulfan-based preparative regimens.
  • Between March 1993 and June 2002, we treated 33 relapsed acute myelogenous leukemia (AML) patients with busulfan-based preparative regimens and selective TCD.
  • Although 67% of evaluable patients developed acute GVHD, severe grade III-IV acute GVHD only developed in 19%.
  • The severity of acute GVHD correlated with the degree of CD8+ TCD.
  • Median relapse-free survival was 5 months among 20 patients treated with active AML, and 28 months among 13 patients treated in complete remission.
  • Our results confirm that MUD BMT with CD8+ TCD for AML is a potentially curative treatment option.
  • [MeSH-major] Bone Marrow Transplantation / methods. Busulfan / administration & dosage. CD8-Positive T-Lymphocytes. Leukemia, Myeloid, Acute / therapy. Lymphocyte Depletion / methods
  • [MeSH-minor] Adult. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carmustine / therapeutic use. Cyclophosphamide / therapeutic use. Etoposide / therapeutic use. Female. Graft Survival. Graft vs Host Disease / prevention & control. Histocompatibility. Histocompatibility Testing. Humans. Male. Middle Aged. Salvage Therapy / methods. Survival Analysis. Tissue Donors. Transplantation Conditioning / methods. Transplantation, Homologous. Treatment Outcome

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  • (PMID = 15580282.001).
  • [ISSN] 0268-3369
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 6PLQ3CP4P3 / Etoposide; 8N3DW7272P / Cyclophosphamide; G1LN9045DK / Busulfan; U68WG3173Y / Carmustine; CBV protocol
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55. Harousseau JL, Lancet JE, Reiffers J, Lowenberg B, Thomas X, Huguet F, Fenaux P, Zhang S, Rackoff W, De Porre P, Stone R, Farnesyltransferase Inhibition Global Human Trials (FIGHT) Acute Myeloid Leukemia Study Group: A phase 2 study of the oral farnesyltransferase inhibitor tipifarnib in patients with refractory or relapsed acute myeloid leukemia. Blood; 2007 Jun 15;109(12):5151-6
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  • [Title] A phase 2 study of the oral farnesyltransferase inhibitor tipifarnib in patients with refractory or relapsed acute myeloid leukemia.
  • This phase 2 study evaluated the efficacy and safety of the oral farnesyltransferase inhibitor tipifarnib in adults with refractory or relapsed acute myeloid leukemia (AML).
  • Single-agent treatment with tipifarnib induced durable CR/CRp, which was associated with prolonged survival, in some patients with refractory or relapsed AML.
  • [MeSH-major] Leukemia, Myeloid / drug therapy. Quinolones / administration & dosage. Salvage Therapy / methods
  • [MeSH-minor] Acute Disease. Adolescent. Adult. Aged. Aged, 80 and over. Antineoplastic Agents / adverse effects. Antineoplastic Agents / therapeutic use. Blast Crisis / pathology. Blast Crisis / prevention & control. Bone Marrow Cells / pathology. Farnesyltranstransferase / antagonists & inhibitors. Female. Humans. Male. Middle Aged. Remission Induction / methods. Survival Rate. Treatment Outcome

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  • (PMID = 17351110.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Quinolones; 192185-72-1 / tipifarnib; EC 2.5.1.29 / Farnesyltranstransferase
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56. Takami A, Okumura H, Yamazaki H, Kami M, Kim SW, Asakura H, Endo T, Nishio M, Minauchi K, Kumano K, Sugimori N, Mori S, Takemoto Y, Shimadoi S, Ozaki J, Takaue Y, Nakao S: Prospective trial of high-dose chemotherapy followed by infusions of peripheral blood stem cells and dose-escalated donor lymphocytes for relapsed leukemia after allogeneic stem cell transplantation. Int J Hematol; 2005 Dec;82(5):449-55
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  • [Title] Prospective trial of high-dose chemotherapy followed by infusions of peripheral blood stem cells and dose-escalated donor lymphocytes for relapsed leukemia after allogeneic stem cell transplantation.
  • To determine whether induction of graft-versus-host disease (GVHD) improves the outcome of acute relapsed leukemia after stem cell transplantation (SCT), we used high-dose cytarabine (ara-C) followed by infusions of donor-derived buffy coats containing peripheral blood stem cells to treat 12 patients with relapsed leukemia.
  • Donor lymphocyte infusion (DLI) was repeated at least twice over a 5-week interval for patients in whom grade II to IV acute GVHD did not develop after the first DLI.
  • Grade II to IV acute GVHD developed in 4 (33%) of the patients.
  • Chronic GVHD developed in 3 patients, 2 of whom had not experienced acute GVHD.
  • Four (67%) of the 6 patients who developed grade II to IV acute and/or chronic GVHD after DLI responded, but none of the other 6 patients responded.
  • Four (33%) of the patients (2 with acute myelogenous leukemia [AML] and 2 with acute lymphoblastic leukemia [ALL]) achieved complete remission lasting longer than 4 months after the first DLI, but 3 of them had relapses in bone sites.
  • Of these 4 patients, 1 patient with AML and 2 with ALL were alive 8 to 27 months after DLI.
  • These findings indicate that high-dose ara-C combined with megadose DLI may produce durable remission of acute leukemia that has relapsed after SCT when GVHD is induced.
  • [MeSH-major] Antimetabolites, Antineoplastic / administration & dosage. Cytarabine / administration & dosage. Graft vs Host Disease / therapy. Leukemia / therapy. Lymphocyte Transfusion. Peripheral Blood Stem Cell Transplantation
  • [MeSH-minor] Adult. Disease-Free Survival. Female. Humans. Male. Middle Aged. Prospective Studies. Recurrence. Remission Induction. Transplantation, Homologous. Treatment Outcome

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  • (PMID = 16533751.001).
  • [ISSN] 0925-5710
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 04079A1RDZ / Cytarabine
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57. Schimmer AD, Estey EH, Borthakur G, Carter BZ, Schiller GJ, Tallman MS, Altman JK, Karp JE, Kassis J, Hedley DW, Brandwein J, Xu W, Mak DH, LaCasse E, Jacob C, Morris SJ, Jolivet J, Andreeff M: Phase I/II trial of AEG35156 X-linked inhibitor of apoptosis protein antisense oligonucleotide combined with idarubicin and cytarabine in patients with relapsed or primary refractory acute myeloid leukemia. J Clin Oncol; 2009 Oct 01;27(28):4741-6
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  • [Title] Phase I/II trial of AEG35156 X-linked inhibitor of apoptosis protein antisense oligonucleotide combined with idarubicin and cytarabine in patients with relapsed or primary refractory acute myeloid leukemia.
  • PURPOSE: X-linked inhibitor of apoptosis protein (XIAP) is an inhibitor of caspases 3 and 9 which are overexpressed in acute myeloid leukemia (AML) and may contribute to chemoresistance.
  • PATIENTS AND METHODS: Twenty-four patients with rapidly relapsed or refractory AML were treated with escalating doses of AEG35156 (12 to 250 mg/m(2)) as an intravenous solution over 2 hours and 32 patients were treated with the highest planned dose of 350 mg/m(2) in combination with idarubicin and high-dose cytarabine reinduction chemotherapy.
  • CONCLUSION: At the highest dose tested, AEG35156 knocks down its target and appears very effective when combined with chemotherapy in patients with AML refractory to a single induction regimen.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid / drug therapy
  • [MeSH-minor] Acute Disease. Adult. Aged. Cytarabine / administration & dosage. Cytarabine / adverse effects. Dose-Response Relationship, Drug. Drug Resistance, Neoplasm. Female. Gene Expression Regulation, Neoplastic / drug effects. Humans. Idarubicin / administration & dosage. Idarubicin / adverse effects. Male. Middle Aged. Oligonucleotides / administration & dosage. Peripheral Nervous System Diseases / chemically induced. RNA, Messenger / genetics. RNA, Messenger / metabolism. Recurrence. Reverse Transcriptase Polymerase Chain Reaction. Treatment Outcome. X-Linked Inhibitor of Apoptosis Protein / genetics

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  • (PMID = 19652057.001).
  • [ISSN] 1527-7755
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / P30 CA016672
  • [Publication-type] Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / AEG 35156; 0 / Oligonucleotides; 0 / RNA, Messenger; 0 / X-Linked Inhibitor of Apoptosis Protein; 04079A1RDZ / Cytarabine; ZRP63D75JW / Idarubicin
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58. Miyawaki S, Emi N, Mitani K, Oyashiki K, Kitamura K, Morishita T, Ogawa H, Komatsu N, Soma T, Tamaki T, Kosugi H, Ohnishi K, Mizoguchi H, Hiraoka A, Kodera Y, Ueda R, Morishima Y, Nakagawa M, Tobita T, Sugimoto K, Chiba S, Inoue N, Hamaguchi M, Koga D, Tamaki H, Naoe T, Sugiyama H, Takaku F: [Clinical course of the disease and the level of WT1 mRNA in 191 patients with acute myeloid leukemia (AML): joint research by 23 institutions in Japan]. Rinsho Ketsueki; 2005 Dec;46(12):1279-87
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  • [Title] [Clinical course of the disease and the level of WT1 mRNA in 191 patients with acute myeloid leukemia (AML): joint research by 23 institutions in Japan].
  • We evaluated the clinical course of acute myeloid leukemia (AML) and the levels of WT1 mRNA in 191 AML patients.
  • Of 114 previously untreated patients with AML, 107 cases were positive for WT1 mRNA (93.9% : 107/114).
  • On the other hand, WT1 mRNA was expressed in 87.0% of non-remission cases (47/54), maintaining 50 copies/microg of RNA or higher ("positive").
  • In all 29 cases who relapsed during the follow-up observation period after achieving remission, WT1 mRNA levels declined transiently approximately around the time of achieving remission and then rose again when the disease relapsed.
  • Moreover, we determined the time of elevation of WT1 mRNA in 29 relapsed cases.
  • In 79.3% of relapsed cases (23/29), WT1 mRNA levels rose above 200 copies/microg RNA, 43 days (median) before the diagnosis of "relapse".
  • Given the percent of the correct diagnosis, WT1 mRNA at 200 copies/microg RNA appeared to be a reasonable cut-off level for early detection of AML-relapse.
  • Besides these promising data, this kit is suitable for routine monitoring of AML because this kit utilizes peripheral blood as a test specimen, reducing the patient's burden at the time of collection of clinical samples as compared with bone marrow aspirate.
  • [MeSH-major] Biomarkers, Tumor / blood. Leukemia, Myeloid, Acute / diagnosis. RNA, Messenger / blood. RNA, Neoplasm / blood. WT1 Proteins / genetics
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Early Diagnosis. Female. Humans. Japan. Male. Middle Aged. Monitoring, Physiologic / methods. Neoplasm Recurrence, Local / diagnosis. Neoplasm, Residual / diagnosis. Polymerase Chain Reaction / methods. Reagent Kits, Diagnostic

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  • (PMID = 16447800.001).
  • [ISSN] 0485-1439
  • [Journal-full-title] [Rinshō ketsueki] The Japanese journal of clinical hematology
  • [ISO-abbreviation] Rinsho Ketsueki
  • [Language] jpn
  • [Publication-type] English Abstract; Journal Article; Multicenter Study
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / RNA, Messenger; 0 / RNA, Neoplasm; 0 / Reagent Kits, Diagnostic; 0 / WT1 Proteins
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59. Qin TJ, Xu ZF, Wang JY, Zhou CL, Xiao ZJ: [Clinical study on regimen cyclophosphamide, Ara-C and topotecan (CAT) in treatment of patients with refractory or relapsed acute myelogenous leukemia]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2009 Oct;17(5):1342-6
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  • [Title] [Clinical study on regimen cyclophosphamide, Ara-C and topotecan (CAT) in treatment of patients with refractory or relapsed acute myelogenous leukemia].
  • Up to now, no consensus has been reached on the standard salvage regimen for patients with refractory or relapsed acute myeloid leukemia (AML).
  • This study was purposed to evaluate the efficacy and safety of combination chemotherapy composing of cyclophosphamide (Cy), cytosine arabinoside (Ara-C) and topotecan (CAT regimen) for 37 refractory or relapsed AML patients.
  • Among 18 relapsed cases, 6 cases had CR (33.3%), 2 cases achieved PR (11.1%), and 10 cases were with NR (55.6%).
  • There was no statistically significant difference in RR between refractory and relapsed groups (31.6% and 44.4%, respectively) (p=0.42).
  • Mild non-hematologic toxicities were mainly gastrointestinal, as nausea, vomiting, diarrhea.
  • The incidence of severe (grade III-IV) non-hematologic toxicity, such as oral mucositis and infection was 37.8% and 86.5% respectively.
  • The median OS for responders was longer than that for non-responders (9 vs 2 months respectively, p=0.00).
  • In conclusion, the CAT regimen of lower dose is well tolerated and has certain anti-leukemia effect, and worthy to be further investigated.

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  • (PMID = 19840480.001).
  • [ISSN] 1009-2137
  • [Journal-full-title] Zhongguo shi yan xue ye xue za zhi
  • [ISO-abbreviation] Zhongguo Shi Yan Xue Ye Xue Za Zhi
  • [Language] CHI
  • [Publication-type] Clinical Trial; English Abstract; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] China
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 7M7YKX2N15 / Topotecan; 8N3DW7272P / Cyclophosphamide
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60. Rao AV, Younis IR, Sand GJ, Spasojevic I, Adams DJ, Decastro CM, Gockerman JP, Peterson BL, Petros WP, Moore JO, Rizzieri DA: Phase I evaluation of gemcitabine, mitoxantrone, and their effect on plasma disposition of fludarabine in patients with relapsed or refractory acute myeloid leukemia. Leuk Lymphoma; 2008 Aug;49(8):1523-9
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  • [Title] Phase I evaluation of gemcitabine, mitoxantrone, and their effect on plasma disposition of fludarabine in patients with relapsed or refractory acute myeloid leukemia.
  • Our aim was to estimate the duration of maximum tolerated dose (MTD) duration for gemcitabine given as a continuous infusion in combination with fludarabine and mitoxantrone and to evaluate potential pharmacokinetic (PK) interactions in 17 patients with refractory or relapsed acute myeloid leukaemia (AML).
  • [MeSH-major] Deoxycytidine / analogs & derivatives. Leukemia, Myeloid, Acute / drug therapy. Mitoxantrone / administration & dosage. Vidarabine / analogs & derivatives
  • [MeSH-minor] Adult. Aged. Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Antineoplastic Combined Chemotherapy Protocols / toxicity. Drug Synergism. Female. Half-Life. Humans. Male. Maximum Tolerated Dose. Middle Aged. Salvage Therapy / methods. Tissue Distribution

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  • (PMID = 18766965.001).
  • [ISSN] 1029-2403
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0W860991D6 / Deoxycytidine; B76N6SBZ8R / gemcitabine; BZ114NVM5P / Mitoxantrone; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine
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61. Chantry AD, Snowden JA, Craddock C, Peggs K, Roddie C, Craig JI, Orchard K, Towlson KE, Pearce RM, Marks DI, BSBMT Clinical Trials Committee: Long-term outcomes of myeloablation and autologous transplantation of relapsed acute myeloid leukemia in second remission: a British Society of Blood and Marrow Transplantation registry study. Biol Blood Marrow Transplant; 2006 Dec;12(12):1310-7
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  • [Title] Long-term outcomes of myeloablation and autologous transplantation of relapsed acute myeloid leukemia in second remission: a British Society of Blood and Marrow Transplantation registry study.
  • Relapsed acute myeloid leukemia (AML) in adults has a poor prognosis if treated with chemotherapy alone.
  • The BSBMT registry database was used to retrospectively identify 152 adult patients (age, 16-69 years) with AML in second remission treated with autologous transplantation in 1982-2003.
  • This study provides long-term follow-up data in one of the largest series of patients with standard-risk and good-risk AML in CR2 treated with autologous transplantation and supports earlier observations that long-term survival is achievable in about 1/3 of patients overall and in about 2/3 of patients with M3 with a relatively low NRM.
  • [MeSH-major] Bone Marrow Transplantation / statistics & numerical data. Leukemia, Myeloid / surgery. Peripheral Blood Stem Cell Transplantation / statistics & numerical data. Salvage Therapy. Transplantation Conditioning / statistics & numerical data. Transplantation, Autologous / statistics & numerical data
  • [MeSH-minor] Acute Disease. Adolescent. Adult. Age Factors. Aged. Busulfan / administration & dosage. Busulfan / adverse effects. Cyclophosphamide / administration & dosage. Cyclophosphamide / adverse effects. Etoposide / administration & dosage. Etoposide / adverse effects. Female. Follow-Up Studies. Great Britain / epidemiology. Humans. Kaplan-Meier Estimate. Male. Melphalan / administration & dosage. Melphalan / adverse effects. Middle Aged. Registries / statistics & numerical data. Remission Induction. Retrospective Studies. Risk Factors. Survival Analysis. Whole-Body Irradiation / statistics & numerical data

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  • (PMID = 17162213.001).
  • [ISSN] 1083-8791
  • [Journal-full-title] Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • [ISO-abbreviation] Biol. Blood Marrow Transplant.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 6PLQ3CP4P3 / Etoposide; 8N3DW7272P / Cyclophosphamide; G1LN9045DK / Busulfan; Q41OR9510P / Melphalan
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62. Advani AS, Tiu R, Saunthararajah Y, Maciejewski J, Copelan EA, Sobecks R, Sekeres MA, Bates J, Rush ML, Tripp B, Salvado A, Noon E, Howard M, Jin T, Hsi E, Egorin MJ, Lim K, Cotta CV, Price C, Kalaycio M: A Phase 1 study of imatinib mesylate in combination with cytarabine and daunorubicin for c-kit positive relapsed acute myeloid leukemia. Leuk Res; 2010 Dec;34(12):1622-6
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  • [Title] A Phase 1 study of imatinib mesylate in combination with cytarabine and daunorubicin for c-kit positive relapsed acute myeloid leukemia.
  • The c-kit receptor is expressed in 95% of relapsed acute myeloid leukemias (AMLs) and mediates leukemic proliferation.
  • We conducted a Phase 1 study of the c-kit inhibitor, imatinib mesylate (IM), in combination with cytarabine and daunorubicin (7+3) in c-kit+ relapsed AML.
  • Cytotoxic therapy that includes IM for relapsed AML is well-tolerated and effective.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Leukemia, Myeloid, Acute / prevention & control. Proto-Oncogene Proteins c-kit
  • [MeSH-minor] Adult. Aged. Benzamides. Cytarabine / administration & dosage. Cytarabine / adverse effects. Daunorubicin / administration & dosage. Daunorubicin / adverse effects. Female. Humans. Imatinib Mesylate. Male. Maximum Tolerated Dose. Middle Aged. Phosphorylation / drug effects. Piperazines / administration & dosage. Piperazines / adverse effects. Pyrimidines / administration & dosage. Pyrimidines / adverse effects. Recurrence. STAT5 Transcription Factor / metabolism

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  • [Copyright] Copyright © 2010 Elsevier Ltd. All rights reserved.
  • (PMID = 20427086.001).
  • [ISSN] 1873-5835
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 0 / STAT5 Transcription Factor; 04079A1RDZ / Cytarabine; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Proto-Oncogene Proteins c-kit; ZS7284E0ZP / Daunorubicin
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63. Giles F, Verstovsek S, Faderl S, Vey N, Karp J, Roboz G, Khan KD, Cooper M, Bilgrami SF, Ferrant A, Daenen S, Karsten V, Cahill A, Albitar M, Kantarjian H, O'Brien S, Feldman E: A phase II study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients with very high risk relapsed acute myeloid leukemia. Leuk Res; 2006 Dec;30(12):1591-5
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  • [Title] A phase II study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients with very high risk relapsed acute myeloid leukemia.
  • Cloretazine (VNP40101M) is a sulfonylhydrazine alkylating agent with significant anti-leukemia activity.
  • A multicenter phase II study of cloretazine was conducted in patients with first relapse of acute myeloid leukemia (AML) following an initial complete remission (CR) of less than 12 months.
  • The study cloretazine regimen had minimal activity in a very high risk subset of patients with relapsed AML.
  • [MeSH-major] Hydrazines / administration & dosage. Leukemia, Myeloid / drug therapy. Sulfonamides / administration & dosage
  • [MeSH-minor] Acute Disease. Adolescent. Adult. Aged. Aged, 80 and over. Cohort Studies. Female. Humans. Infusions, Intravenous. Male. Middle Aged. Recurrence. Remission Induction. Risk Factors. Survival Rate. Treatment Outcome

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  • (PMID = 16574225.001).
  • [ISSN] 0145-2126
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Letter; Multicenter Study
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Hydrazines; 0 / Sulfonamides; 14J2G0U3NQ / laromustine
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64. Litzow MR, Othus M, Cripe LD, Gore SD, Lazarus HM, Lee SJ, Bennett JM, Paietta EM, Dewald GW, Rowe JM, Tallman MS, Eastern Cooperative Oncology Group Leukemia Committee: Failure of three novel regimens to improve outcome for patients with relapsed or refractory acute myeloid leukaemia: a report from the Eastern Cooperative Oncology Group. Br J Haematol; 2010 Jan;148(2):217-25
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  • [Title] Failure of three novel regimens to improve outcome for patients with relapsed or refractory acute myeloid leukaemia: a report from the Eastern Cooperative Oncology Group.
  • The treatment of relapsed acute myeloid leukaemia (AML) remains unsatisfactory.
  • Eligible patients had primary refractory AML, a first relapse after a remission of <1 year, or a second or greater relapse.
  • No patients who had relapsed within 6 months of initial CR or who had suffered multiple relapses responded.
  • More than 95% of patients subsequently died of AML.
  • We conclude that none of these three regimens were effective enough in the treatment of high-risk relapsed or refractory AML to warrant further study.
  • [MeSH-major] Antimetabolites, Antineoplastic / therapeutic use. Antineoplastic Agents / therapeutic use. Immunosuppressive Agents / therapeutic use. Leukemia, Myeloid, Acute / drug therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Aminoglycosides / therapeutic use. Antibodies, Monoclonal / therapeutic use. Antibodies, Monoclonal, Humanized. Cyclophosphamide / therapeutic use. Cytarabine / therapeutic use. Daunorubicin / administration & dosage. Daunorubicin / therapeutic use. Drug Therapy, Combination. Female. Humans. Liposomes. Male. Middle Aged. Recurrence. Remission Induction. Survival Analysis. Topotecan / therapeutic use

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  • (PMID = 19804455.001).
  • [ISSN] 1365-2141
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Databank-accession-numbers] ClinicalTrials.gov/ NCT00005962
  • [Grant] United States / NCI NIH HHS / CA / T32 CA009337; United States / NCI NIH HHS / CA / CA14958; United States / NCI NIH HHS / CA / CA14548; United States / NCI NIH HHS / CA / U10 CA013650; United States / NCI NIH HHS / CA / U10 CA014958; United States / NCI NIH HHS / CA / CA66636; United States / NCI NIH HHS / CA / U10 CA021115; United States / NCI NIH HHS / CA / U10 CA049883; United States / NCI NIH HHS / CA / CA13650; United States / NCI NIH HHS / CA / U10 CA017145; United States / NCI NIH HHS / CA / U10 CA021115-31; United States / NCI NIH HHS / CA / CA11083; United States / NCI NIH HHS / CA / U10 CA066636; United States / NCI NIH HHS / CA / CA17145; United States / NCI NIH HHS / CA / U10 CA016116; United States / NCI NIH HHS / CA / U10 CA014548; United States / NCI NIH HHS / CA / U10 CA023318; United States / NCI NIH HHS / CA / U10 CA011083; United States / NCI NIH HHS / CA / CA49883; United States / NCI NIH HHS / CA / CA21115; United States / NCI NIH HHS / CA / U24 CA114737; United States / NCI NIH HHS / CA / CA23318; United States / NCI NIH HHS / CA / CA16116
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Aminoglycosides; 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antimetabolites, Antineoplastic; 0 / Antineoplastic Agents; 0 / Immunosuppressive Agents; 0 / Liposomes; 04079A1RDZ / Cytarabine; 7M7YKX2N15 / Topotecan; 8N3DW7272P / Cyclophosphamide; 93NS566KF7 / gemtuzumab; ZS7284E0ZP / Daunorubicin
  • [Other-IDs] NLM/ NIHMS152429; NLM/ PMC2809127
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65. Kobayashi K, Kami M, Murashige N, Kusumi E, Kishi Y, Hamaki T, Hori A, Matsumura T, Yuji K, Masuo S, Mori S, Miyakoshi S, Tanosaki R, Mitamura T, Takaue Y, Taniguchi S, Tokyo SCT Consortium Institution: Outcomes of patients with acute leukaemia who relapsed after reduced-intensity stem cell transplantation from HLA-identical or one antigen-mismatched related donors. Br J Haematol; 2005 Jun;129(6):795-802
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  • [Title] Outcomes of patients with acute leukaemia who relapsed after reduced-intensity stem cell transplantation from HLA-identical or one antigen-mismatched related donors.
  • We reviewed the medical records of 19 patients with acute leukaemia [acute myeloid leukaemia (AML), 16; acute lymphoblastic leukaemia (ALL), 3] who relapsed after RIST from related donors using purine-analogue-based regimens.
  • Cumulative incidences of relapse-related and non-relapse-related deaths at 2 years after relapse were 37% and 32% respectively.
  • Some AML patients who relapse after RIST achieve durable remission with allogeneic immunotherapy-based interventions; however they carry a significant risk of non-relapse mortality.
  • [MeSH-major] HLA Antigens / analysis. Hematopoietic Stem Cell Transplantation / methods. Leukemia, Myeloid / therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • [MeSH-minor] Acute Disease. Adult. Aged. Cause of Death. Female. Graft vs Host Disease / etiology. Histocompatibility Testing. Humans. Male. Middle Aged. Prognosis. Recurrence. Retrospective Studies. Survival Analysis. Treatment Outcome

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  • (PMID = 15953007.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / HLA Antigens
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66. Milligan DW, Wheatley K, Littlewood T, Craig JI, Burnett AK, NCRI Haematological Oncology Clinical Studies Group: Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial. Blood; 2006 Jun 15;107(12):4614-22
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  • [Title] Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial.
  • The optimum chemotherapy schedule for reinduction of patients with high-risk acute myeloid leukemia (relapsed, resistant/refractory, or adverse genetic disease) is uncertain.
  • The MRC AML (Medical Research Council Acute Myeloid Leukemia) Working Group designed a trial comparing fludarabine and high-dose cytosine (FLA) with standard chemotherapy comprising cytosine arabinoside, daunorubicin, and etoposide (ADE).
  • In conclusion these findings indicate that FLA may be inferior to standard chemotherapy in high-risk AML and that the outcome is not improved with the addition of either G-CSF or ATRA.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Granulocyte Colony-Stimulating Factor / administration & dosage. Leukemia, Myeloid, Acute / drug therapy. Tretinoin / administration & dosage
  • [MeSH-minor] Adolescent. Adult. Aged. Cytarabine / administration & dosage. Daunorubicin / administration & dosage. Disease-Free Survival. Etoposide / administration & dosage. Female. Filgrastim. Humans. Male. Middle Aged. Recombinant Proteins. Remission Induction. Retrospective Studies. Risk Factors. Survival Rate. Treatment Outcome

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  • [CommentIn] Blood. 2006 Dec 1;108(12):3950-1; author reply 3951 [17114571.001]
  • (PMID = 16484584.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Grant] United Kingdom / Medical Research Council / / G0300133
  • [Publication-type] Comparative Study; Journal Article; Randomized Controlled Trial
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Recombinant Proteins; 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 5688UTC01R / Tretinoin; 6PLQ3CP4P3 / Etoposide; PVI5M0M1GW / Filgrastim; ZS7284E0ZP / Daunorubicin; DAV regimen
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67. Perl AE, Kasner MT, Tsai DE, Vogl DT, Loren AW, Schuster SJ, Porter DL, Stadtmauer EA, Goldstein SC, Frey NV, Nasta SD, Hexner EO, Dierov JK, Swider CR, Bagg A, Gewirtz AM, Carroll M, Luger SM: A phase I study of the mammalian target of rapamycin inhibitor sirolimus and MEC chemotherapy in relapsed and refractory acute myelogenous leukemia. Clin Cancer Res; 2009 Nov 1;15(21):6732-9
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  • [Title] A phase I study of the mammalian target of rapamycin inhibitor sirolimus and MEC chemotherapy in relapsed and refractory acute myelogenous leukemia.
  • PURPOSE: Inhibiting mammalian target of rapamycin (mTOR) signaling in acute myelogenous leukemia (AML) blasts and leukemic stem cells may enhance their sensitivity to cytotoxic agents.
  • We sought to determine the safety and describe the toxicity of this approach by adding the mTOR inhibitor, sirolimus (rapamycin), to intensive AML induction chemotherapy.
  • EXPERIMENTAL DESIGN: We performed a phase I dose escalation study of sirolimus with the chemotherapy regimen MEC (mitoxantrone, etoposide, and cytarabine) in patients with relapsed, refractory, or untreated secondary AML.
  • Future studies are planned with different schedules to clarify the clinical and biochemical effects of sirolimus in AML and to determine whether target inhibition predicts chemotherapy response.
  • [MeSH-major] Antibiotics, Antineoplastic / administration & dosage. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid, Acute / drug therapy. Sirolimus / administration & dosage
  • [MeSH-minor] Adult. Aged. Carboplatin / therapeutic use. Drug Administration Schedule. Drug Resistance, Neoplasm. Etoposide / therapeutic use. Female. Humans. Male. Maximum Tolerated Dose. Melphalan / therapeutic use. Middle Aged. Protein Kinases / metabolism. Recurrence. Signal Transduction. TOR Serine-Threonine Kinases

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  • (PMID = 19843663.001).
  • [ISSN] 1078-0432
  • [Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research
  • [ISO-abbreviation] Clin. Cancer Res.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibiotics, Antineoplastic; 6PLQ3CP4P3 / Etoposide; BG3F62OND5 / Carboplatin; EC 2.7.- / Protein Kinases; EC 2.7.1.1 / MTOR protein, human; EC 2.7.1.1 / TOR Serine-Threonine Kinases; Q41OR9510P / Melphalan; W36ZG6FT64 / Sirolimus; MEC regimen
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68. Angiolillo AL, Whitlock J, Chen Z, Krailo M, Reaman G, Children's Oncology Group: Phase II study of gemcitabine in children with relapsed acute lymphoblastic leukemia or acute myelogenous leukemia (ADVL0022): a Children's Oncology Group Report. Pediatr Blood Cancer; 2006 Feb;46(2):193-7
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  • [Title] Phase II study of gemcitabine in children with relapsed acute lymphoblastic leukemia or acute myelogenous leukemia (ADVL0022): a Children's Oncology Group Report.
  • BACKGROUND: To determine the response rate and toxicity to gemcitabine administered as 10 mg/m2/min x 360 min weekly for 3 weeks in children with relapsed acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML).
  • RESULTS: One of 20 evaluable patients with ALL and none of 10 evaluable patients with AML had complete responses to gemcitabine; there were no partial responses.
  • CONCLUSIONS: Gemcitabine at the dose and schedule in this trial was not effective for children with relapsed AML or ALL.
  • [MeSH-major] Antimetabolites, Antineoplastic / administration & dosage. Deoxycytidine / analogs & derivatives. Leukemia, Myeloid, Acute / prevention & control. Precursor Cell Lymphoblastic Leukemia-Lymphoma / prevention & control
  • [MeSH-minor] Adolescent. Adult. Child. Child, Preschool. Disease-Free Survival. Female. Humans. Infant. Male. Recurrence. Treatment Failure


69. Feldman EJ, Brandwein J, Stone R, Kalaycio M, Moore J, O'Connor J, Wedel N, Roboz GJ, Miller C, Chopra R, Jurcic JC, Brown R, Ehmann WC, Schulman P, Frankel SR, De Angelo D, Scheinberg D: Phase III randomized multicenter study of a humanized anti-CD33 monoclonal antibody, lintuzumab, in combination with chemotherapy, versus chemotherapy alone in patients with refractory or first-relapsed acute myeloid leukemia. J Clin Oncol; 2005 Jun 20;23(18):4110-6
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  • [Title] Phase III randomized multicenter study of a humanized anti-CD33 monoclonal antibody, lintuzumab, in combination with chemotherapy, versus chemotherapy alone in patients with refractory or first-relapsed acute myeloid leukemia.
  • In this study, the efficacy of lintuzumab in combination with induction chemotherapy was compared with chemotherapy alone in adults with first relapsed or primary refractory acute myeloid leukemia (AML).
  • PATIENTS AND METHODS: Patients with relapsed or primary resistant AML (duration of first response, zero to 12 months) were randomly assigned to receive either mitoxantrone 8 mg/m(2), etoposide 80 mg/m(2), and cytarabine 1 g/m(2) daily for 6 days (MEC) in combination with lintuzumab 12 mg/m(2), or MEC alone.
  • CONCLUSION: The addition of lintuzumab to salvage induction chemotherapy was safe, but did not result in a statistically significant improvement in response rate or survival in patients with refractory/relapsed AML.
  • [MeSH-major] Antibodies, Monoclonal / administration & dosage. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid, Acute / drug therapy
  • [MeSH-minor] Adult. Aged. Antibodies, Monoclonal, Humanized. Cytarabine / administration & dosage. Etoposide / administration & dosage. Female. Humans. Male. Middle Aged. Mitoxantrone / administration & dosage. Proportional Hazards Models. Recurrence. Survival Analysis. Treatment Outcome

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  • (PMID = 15961759.001).
  • [ISSN] 0732-183X
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / lintuzumab; 04079A1RDZ / Cytarabine; 6PLQ3CP4P3 / Etoposide; BZ114NVM5P / Mitoxantrone
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70. Wierzbowska A, Robak T, Pluta A, Wawrzyniak E, Cebula B, Hołowiecki J, Kyrcz-Krzemień S, Grosicki S, Giebel S, Skotnicki AB, Piatkowska-Jakubas B, Kuliczkowski K, Kiełbiński M, Zawilska K, Kłoczko J, Wrzesień-Kuś A, Polish Adult Leukemia Group: Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol; 2008 Feb;80(2):115-26
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  • [Title] Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group.
  • OBJECTIVES: Patients with primary refractory AML and with early relapses have unfavorable prognoses and require innovative therapeutic approaches.
  • In the current report, we present the final results of multi-center phase II study evaluating the efficacy and toxicity of CLAG-M salvage regimen in poor risk refractory/relapsed AML patients.
  • RESULTS: One hundred and eighteen patients from 11 centers were registered; 78 primary resistant and 40 relapsed.
  • CONCLUSIONS: We conclude that CLAG-M is a well-tolerated and highly effective salvage regimen in poor risk refractory/relapsed AML.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cladribine / administration & dosage. Cytarabine / administration & dosage. Granulocyte Colony-Stimulating Factor / administration & dosage. Leukemia, Myeloid, Acute / drug therapy. Mitoxantrone / administration & dosage. Salvage Therapy / methods
  • [MeSH-minor] Adult. Aged. Female. Humans. Male. Middle Aged. Multivariate Analysis. Odds Ratio. Poland. Recurrence. Stem Cell Transplantation. Treatment Outcome

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  • (PMID = 18076637.001).
  • [ISSN] 1600-0609
  • [Journal-full-title] European journal of haematology
  • [ISO-abbreviation] Eur. J. Haematol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Denmark
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 47M74X9YT5 / Cladribine; BZ114NVM5P / Mitoxantrone
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71. Kuendgen A, Knipp S, Fox F, Strupp C, Hildebrandt B, Steidl C, Germing U, Haas R, Gattermann N: Results of a phase 2 study of valproic acid alone or in combination with all-trans retinoic acid in 75 patients with myelodysplastic syndrome and relapsed or refractory acute myeloid leukemia. Ann Hematol; 2005 Dec;84 Suppl 1:61-6
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  • [Title] Results of a phase 2 study of valproic acid alone or in combination with all-trans retinoic acid in 75 patients with myelodysplastic syndrome and relapsed or refractory acute myeloid leukemia.
  • Valproic acid (VPA) inhibits histone deacetylase activity and induces differentiation of acute myeloid leukemia (AML) blasts in vitro.
  • We observed clinical responses to VPA in patients with myelodysplastic syndrome (MDS) and AML.
  • Of these, 66 were started on VPA monotherapy, with later addition of all-trans retinoic acid (ATRA) in patients who did not respond or relapsed.
  • However, of ten VPA responders who relapsed, four achieved a second response after addition of ATRA.
  • The response rate was 6% in refractory anemia with excess blasts (I + II), 16% in AML, and 0% in chronic myelomonocytic leukemia.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Histone Deacetylase Inhibitors. Leukemia, Myeloid / drug therapy. Myelodysplastic Syndromes / drug therapy. Valproic Acid / therapeutic use
  • [MeSH-minor] Acute Disease. Adult. Aged. Aged, 80 and over. Cell Differentiation / drug effects. Female. Histone Deacetylases / drug effects. Humans. Kaplan-Meier Estimate. Male. Middle Aged. Remission Induction. Treatment Outcome. Tretinoin / administration & dosage


72. Brethon B, Auvrignon A, Galambrun C, Yakouben K, Leblanc T, Bertrand Y, Leverger G, Baruchel A: Efficacy and tolerability of gemtuzumab ozogamicin (anti-CD33 monoclonal antibody, CMA-676, Mylotarg) in children with relapsed/refractory myeloid leukemia. BMC Cancer; 2006;6:172
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  • [Title] Efficacy and tolerability of gemtuzumab ozogamicin (anti-CD33 monoclonal antibody, CMA-676, Mylotarg) in children with relapsed/refractory myeloid leukemia.
  • BACKGROUND: Gemtuzumab ozogamicin (GO) is a cytotoxic anti-CD33 monoclonal antibody that has given promising preliminary results in adult myeloid CD33+ AML.
  • Three patients (2 MDS/AML, 1 JMML) were refractory to first-line treatment, 8 patients with de novo AML were in refractory first relapse, and one patient with de novo AML was in 2nd relapse after stem cell transplantation (SCT).
  • CONCLUSION: These results warrant a prospective trial of GO in a larger population of children with AML.
  • [MeSH-major] Aminoglycosides / therapeutic use. Antibodies, Monoclonal / therapeutic use. Antineoplastic Agents / therapeutic use. Immunotoxins / therapeutic use. Leukemia, Myeloid / drug therapy

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  • (PMID = 16805911.001).
  • [ISSN] 1471-2407
  • [Journal-full-title] BMC cancer
  • [ISO-abbreviation] BMC Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Multicenter Study
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Aminoglycosides; 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antigens, CD; 0 / Antigens, Differentiation, Myelomonocytic; 0 / Antineoplastic Agents; 0 / CD33 protein, human; 0 / Immunotoxins; 0 / Sialic Acid Binding Ig-like Lectin 3; 0 / gemtuzumab
  • [Other-IDs] NLM/ PMC1523361
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73. Lübbert M, Bertz H, Wäsch R, Marks R, Rüter B, Claus R, Finke J: Efficacy of a 3-day, low-dose treatment with 5-azacytidine followed by donor lymphocyte infusions in older patients with acute myeloid leukemia or chronic myelomonocytic leukemia relapsed after allografting. Bone Marrow Transplant; 2010 Apr;45(4):627-32
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  • [Title] Efficacy of a 3-day, low-dose treatment with 5-azacytidine followed by donor lymphocyte infusions in older patients with acute myeloid leukemia or chronic myelomonocytic leukemia relapsed after allografting.
  • We have piloted a low-dose schedule of 5-azacytidine followed by donor lymphocyte infusions (DLIs) in patients with relapse of AML or chronic myelomonocytic leukemia (CMMoL) after allografting.
  • Of the 26 patients (median age 62 years, range 28-75) with relapsed AML (n=24) or CMMoL (n=2), 11 (42%) had poor-risk cytogenetics.
  • Only two patients developed de novo acute GvHD after the combination of 5-azacytidine and DLI.
  • In conclusion, this non-intensive outpatient regimen of 5-azacytidine followed by DLI is feasible, with a very low aGVHD rate.
  • [MeSH-major] Antimetabolites, Antineoplastic / administration & dosage. Azacitidine / administration & dosage. Leukemia, Myeloid, Acute / therapy. Leukemia, Myelomonocytic, Chronic / therapy. Lymphocyte Transfusion. Transplantation Conditioning
  • [MeSH-minor] Adult. Aged. DNA Methylation. Drug Administration Schedule. Epigenesis, Genetic. Female. Graft vs Host Disease. Humans. Kaplan-Meier Estimate. Male. Middle Aged. Neoplasm Recurrence, Local / therapy. Pilot Projects. Stem Cell Transplantation. Transplantation Chimera. Transplantation, Homologous


74. Pollyea DA, Artz AS, Stock W, Daugherty C, Godley L, Odenike OM, Rich E, Smith SM, Zimmerman T, Zhang Y, Huo D, Larson R, van Besien K: Outcomes of patients with AML and MDS who relapse or progress after reduced intensity allogeneic hematopoietic cell transplantation. Bone Marrow Transplant; 2007 Dec;40(11):1027-32
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  • [Title] Outcomes of patients with AML and MDS who relapse or progress after reduced intensity allogeneic hematopoietic cell transplantation.
  • Seventy consecutive patients with high-risk myeloid malignancies underwent transplant and 25 (36%) relapsed, a median of 120 days later.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation / adverse effects. Leukemia, Myeloid, Acute / therapy. Myelodysplastic Syndromes / therapy. Neoplasm Recurrence, Local / therapy. Salvage Therapy / methods
  • [MeSH-minor] Adult. Aged. Antibodies, Monoclonal / therapeutic use. Antibodies, Monoclonal, Humanized. Antibodies, Neoplasm / therapeutic use. Female. Humans. Male. Melphalan / therapeutic use. Middle Aged. Prognosis. Survival Analysis. Transplantation Conditioning / adverse effects. Transplantation Conditioning / methods. Treatment Outcome. Vidarabine / analogs & derivatives. Vidarabine / therapeutic use

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  • (PMID = 17846595.001).
  • [ISSN] 0268-3369
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antibodies, Neoplasm; 3A189DH42V / alemtuzumab; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine; Q41OR9510P / Melphalan
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75. O'Brien MM, Lacayo NJ, Lum BL, Kshirsagar S, Buck S, Ravindranath Y, Bernstein M, Weinstein H, Chang MN, Arceci RJ, Sikic BI, Dahl GV: Phase I study of valspodar (PSC-833) with mitoxantrone and etoposide in refractory and relapsed pediatric acute leukemia: a report from the Children's Oncology Group. Pediatr Blood Cancer; 2010 May;54(5):694-702
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  • [Title] Phase I study of valspodar (PSC-833) with mitoxantrone and etoposide in refractory and relapsed pediatric acute leukemia: a report from the Children's Oncology Group.
  • BACKGROUND: Valspodar, a non-immunosuppressive analog of cylosporine, is a potent P-glycoprotein (MDR1) inhibitor.
  • As MDR1-mediated efflux of chemotherapeutic agents from leukemic blasts may contribute to drug resistance, a phase 1 study of valspodar combined with mitoxantrone and etoposide in pediatric patients with relapsed or refractory leukemias was performed.
  • Three of 11 patients with acute lymphoblastic leukemia (ALL) had complete responses while no patient with acute myeloid leukemia (AML) had an objective response.

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  • (PMID = 20209646.001).
  • [ISSN] 1545-5017
  • [Journal-full-title] Pediatric blood & cancer
  • [ISO-abbreviation] Pediatr Blood Cancer
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R01 CA052168-12S1; United States / NCI NIH HHS / CA / U10 CA98413; United States / PHS HHS / / R01 52168; United States / NCI NIH HHS / CA / U10 CA098413; United States / NCRR NIH HHS / RR / M01 RR 00070; United States / NCI NIH HHS / CA / U10 CA098543; United States / NCI NIH HHS / CA / R01 CA052168; United States / NCRR NIH HHS / RR / M01 RR000070; United States / NCI NIH HHS / CA / U10 CA98543
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Cyclosporins; 0 / P-Glycoprotein; 121584-18-7 / valspodar; 6PLQ3CP4P3 / Etoposide; BZ114NVM5P / Mitoxantrone
  • [Other-IDs] NLM/ NIHMS155713; NLM/ PMC2838930
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76. Li JM, Shen Y, Wu DP, Liang H, Jin J, Chen FY, Song YP, Song EY, Qiu XF, Hou M, Qiu ZC, Shen ZX: Aclarubicin and low-dose Cytosine arabinoside in combination with granulocyte colony-stimulating factor in treating acute myeloid leukemia patients with relapsed or refractory disease and myelodysplastic syndrome: a multicenter study of 112 Chinese patients. Int J Hematol; 2005 Jul;82(1):48-54
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  • [Title] Aclarubicin and low-dose Cytosine arabinoside in combination with granulocyte colony-stimulating factor in treating acute myeloid leukemia patients with relapsed or refractory disease and myelodysplastic syndrome: a multicenter study of 112 Chinese patients.
  • One hundred twelve patients with geriatric acute myeloid leukemia (AML), refractory or relapsed AML, or myelodysplastic syndrome and refractory anemia with excess of blasts in transformation (MDS-RAEBt) were entered into this study to receive CAG (aclarubicin and low-dose cytosine arabinoside [Ara-C]in combination with granulocyte colony-stimulating factor [G-CSF]) with the objective of evaluating the efficacy and tolerance of this regimen.
  • We demonstrated comparable overall complete remission rates for the 4 groups of patients: 30.8% (8/26) in the elderly patients, 48.4% (30/62) in the refractory AML patients, 44.4% (8/18) in the relapsed AML patients, and 38.5% (5/13) in the MDS-RAEBt patients.
  • The CAG regimen seems promising, with acceptable toxicity, for the treatment of various categories of poor-prognosis AML and MDS-RAEBt.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid / drug therapy. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Aclarubicin / administration & dosage. Acute Disease. Adolescent. Adult. Aged. Aged, 80 and over. Cytarabine / administration & dosage. Dose-Response Relationship, Drug. Female. Granulocyte Colony-Stimulating Factor / administration & dosage. Humans. Injections, Subcutaneous. Male. Middle Aged. Neutropenia / chemically induced. Survival Analysis. Thrombocytopenia / chemically induced. Treatment Outcome


77. Bishton MJ, Leahy MF, Hicks RJ, Turner JH, McQuillan AD, Seymour JF: Repeat treatment with iodine-131-rituximab is safe and effective in patients with relapsed indolent B-cell non-Hodgkin's lymphoma who had previously responded to iodine-131-rituximab. Ann Oncol; 2008 Sep;19(9):1629-33
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  • [Title] Repeat treatment with iodine-131-rituximab is safe and effective in patients with relapsed indolent B-cell non-Hodgkin's lymphoma who had previously responded to iodine-131-rituximab.
  • The severity of cytopenia, development of myelodysplasia (MDS), acute myeloid leukemia (AML) and hypothyroidism was noted.
  • One patient developed AML, with no other cases of MDS.

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  • (PMID = 18522934.001).
  • [ISSN] 1569-8041
  • [Journal-full-title] Annals of oncology : official journal of the European Society for Medical Oncology
  • [ISO-abbreviation] Ann. Oncol.
  • [Language] ENG
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Antigens, CD20; 0 / Iodine Radioisotopes; 4F4X42SYQ6 / Rituximab
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78. Taksin AL, Legrand O, Raffoux E, de Revel T, Thomas X, Contentin N, Bouabdallah R, Pautas C, Turlure P, Reman O, Gardin C, Varet B, de Botton S, Pousset F, Farhat H, Chevret S, Dombret H, Castaigne S: High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the alfa group. Leukemia; 2007 Jan;21(1):66-71
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  • [Title] High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the alfa group.
  • Pivotal phase II studies in acute myeloblastic leukemia (AML) patients in first relapse have used gemtuzumab ozogamicin (GO) (Mylotarg) at a dose of 9 mg/m(2) on days 1 and 14.
  • Fifty-seven patients with AML in first relapse received GO at a dose of 3 mg/m(2) on days 1, 4 and 7 for one course.
  • [MeSH-major] Aminoglycosides / administration & dosage. Antibodies, Monoclonal / administration & dosage. Antineoplastic Agents / administration & dosage. Leukemia, Myeloid, Acute / drug therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Antibodies, Monoclonal, Humanized. Antigens, CD / blood. Antigens, Differentiation, Myelomonocytic / blood. Disease-Free Survival. Drug Administration Schedule. Humans. Middle Aged. Multidrug Resistance-Associated Proteins / blood. P-Glycoprotein / blood. Recurrence. Remission Induction. Sialic Acid Binding Ig-like Lectin 3

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  • (PMID = 17051246.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Multicenter Study
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Aminoglycosides; 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antigens, CD; 0 / Antigens, Differentiation, Myelomonocytic; 0 / Antineoplastic Agents; 0 / CD33 protein, human; 0 / Multidrug Resistance-Associated Proteins; 0 / P-Glycoprotein; 0 / Sialic Acid Binding Ig-like Lectin 3; 0 / gemtuzumab; 0 / multidrug resistance-associated protein 1
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79. Fan LP, Shen JZ, Ye BG, Lin FA, Fu HY, Zhou HR, Shen SF, Yu AF: [Detection of p16 gene methylation status in adult patients with acute leukemia by using n-MSP]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2007 Apr;15(2):258-61
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  • [Title] [Detection of p16 gene methylation status in adult patients with acute leukemia by using n-MSP].
  • The study was aimed to explore the relationship between patterns of methylation or deletion and the development of acute leukemia, and further to clarify the possible mechanism in the development of adult acute leukemia.
  • Nested methylation-specific polymerase chain reaction (n-MSP) was adopted to analyze p16 gene methylation or deletion patterns in 82 adult acute leukemia patients with different subtypes and stages.
  • The results indicated that rate of p16 gene methylation was 39.0% in 82 adult acute leukemia patients, among them, 41.4% in acute myelogenous leukemia (AML) and 33.3% in acute lymphoblastic leukemia (ALL).
  • It were found that 36.6% of de novo AL patients and 54.5% of relapsed AL patients developed the hypermethylation of p16 gene.
  • Out of the 82 patients, 6 seemed to have deletion of p16 gene, including 1 AML (1.7%) and 5 ALL (20.8%).
  • It is concluded that methylation of p16 gene may play a more important role than homozygous deletion of p16 gene in the leukemogenesis and progression of adult acute leukemia.

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  • (PMID = 17493327.001).
  • [ISSN] 1009-2137
  • [Journal-full-title] Zhongguo shi yan xue ye xue za zhi
  • [ISO-abbreviation] Zhongguo Shi Yan Xue Ye Xue Za Zhi
  • [Language] CHI
  • [Publication-type] English Abstract; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] China
  • [Chemical-registry-number] 0 / DNA, Neoplasm
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80. Zhou PY, Li WJ, Wei CX, Zhou Z: [Expression of PRAME gene in adult acute leukemia and its significance in prognosis]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2007 Dec;15(6):1177-81
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  • [Title] [Expression of PRAME gene in adult acute leukemia and its significance in prognosis].
  • The study was aimed to investigate the expression of preferentially expressed antigen of melanoma (PRAME) gene in adult acute leukemia and its clinical significance.
  • The expression of the PRAME gene of bone marrow was measured by reverse transcriptase polymerase chain reaction (RT-PCR) in 73 adult newly diagnosed acute leukemia patients, 3 relapsed patients, 7 patients with idiopathic thrombocytopenic purpura (ITP) and 8 healthy donors, as well as two AL cell-lines (K562 and U937).
  • The results indicated that PRAME mRNA was expressed in 42.9% AML patients (n=24) and 20% ALL patients (n=4), also in two leukemia cell-lines K562 and U937, but not in eight health donors and seven ITP patients.
  • PRAME gene was overexpressed in adult acute leukemia patients and leukemia cell-lines.
  • It is concluded that the expression of PRAME is an indicator of favorable prognosis and can be a useful tool for monitoring minimal residual disease (MRD) in adult acute leukemia.
  • Differential expression between adult acute leukemia patients and healthy volunteers suggests that the immunogenic antigens PRAME are potential candidates for immunotherapy in adult acute leukemia.

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  • (PMID = 18088461.001).
  • [ISSN] 1009-2137
  • [Journal-full-title] Zhongguo shi yan xue ye xue za zhi
  • [ISO-abbreviation] Zhongguo Shi Yan Xue Ye Xue Za Zhi
  • [Language] CHI
  • [Publication-type] English Abstract; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Antigens, Neoplasm; 0 / PRAME protein, human; 0 / RNA, Messenger
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81. Styczynski J, Gil L, Derwich K, Wachowiak J, Balwierz W, Badowska W, Krawczuk-Rybak M, Matysiak M, Wieczorek M, Balcerska A, Sonta-Jakimczyk D, Stefaniak J, Kowalczyk J, Urasinski T, Sobol G, Komarnicki M, Wysocki M: Comparison of clofarabine activity in childhood and adult acute leukemia: individual tumor response study. Anticancer Res; 2009 May;29(5):1643-50
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  • [Title] Comparison of clofarabine activity in childhood and adult acute leukemia: individual tumor response study.
  • The aim of the study was the analysis of ex vivo activity of clofarabine and 14 other anticancer drugs in pediatric and adult acute lymphoblastic (ALL) and myeloid (AML) leukemia.
  • PATIENTS AND METHODS: The ex vivo drug resistance profile was analyzed in 282 patients, including 201 children with ALL de novo, 24 children with relapsed ALL, 25 children with AML de novo and 32 adults with AML.
  • Its activity in acute myeloid leukemia was independent of patient age.
  • An activity of clofarabine in relapsed pediatric ALL patients was as good as in newly-diagnosed ones.
  • CONCLUSION: In comparison to childhood acute lymphoblastic leukemia, lack of differences in ex vivo activity gives rationale for use of clofarabine in refractory and relapsed pediatric and adult patients with acute myeloid leukemia.
  • [MeSH-major] Adenine Nucleotides / therapeutic use. Antineoplastic Agents / therapeutic use. Arabinonucleosides / therapeutic use. Leukemia / drug therapy
  • [MeSH-minor] Acute Disease. Adolescent. Adult. Child. Child, Preschool. Humans. Infant. Middle Aged. Treatment Outcome. Young Adult

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  • (PMID = 19443380.001).
  • [ISSN] 0250-7005
  • [Journal-full-title] Anticancer research
  • [ISO-abbreviation] Anticancer Res.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Greece
  • [Chemical-registry-number] 0 / Adenine Nucleotides; 0 / Antineoplastic Agents; 0 / Arabinonucleosides; 762RDY0Y2H / clofarabine
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82. Chevallier P, Mahe B, Garand R, Talmant P, Harousseau JL, Delaunay J: Combination of chemotherapy and gemtuzumab ozogamicin in adult Philadelphia positive acute lymphoblastic leukemia patient harboring CD33 expression. Int J Hematol; 2008 Sep;88(2):209-11
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  • [Title] Combination of chemotherapy and gemtuzumab ozogamicin in adult Philadelphia positive acute lymphoblastic leukemia patient harboring CD33 expression.
  • It was developed at the end of the nineties as 90% of the leukemic blast population of patients with acute myeloid leukaemia (AML) express the CD33 surface antigen (Dinndorf et al. [1] Blood 1986;67:1048-53).
  • GO is currently approved in monotherapy for the treatment of CD33+ AML patients in first relapse, showing a 26% overall response rate and a median disease-free-survival of 5.2 months for responders (Larson et al. [2] Cancer 2005;104:1442-52).
  • CD33 antigen expression is also observed at diagnosis (in 15% of cases) (Pui et al. [3] J Clin Oncol 1998;16:3768-73) or at relapse (Guglielmi et al. [4] Leukemia 1997; 11:1501-7) of acute lymphoblastic leukaemia (ALL), representing a potential cellular target for ALL patients.
  • Case series have already demonstrated the efficacy of GO in children with relapsed CD33+ ALL with documentation of complete remission (CR) (Balduzzi et al. [5] Leukemia 2003;17:2247-8; Cotter et al. [6] Br J Haematol 2003;122:686-91; Zwaan et al. [7] Leukemia 2003;17:468-70).
  • In the other hand, there is no report at our knowledge of the use of GO in the setting of adult CD33+ ALL patient.
  • [MeSH-major] Aminoglycosides / administration & dosage. Antibodies, Monoclonal / administration & dosage. Antineoplastic Agents / administration & dosage. Philadelphia Chromosome. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • [MeSH-minor] Adult. Antibodies, Monoclonal, Humanized. Antigens, CD / metabolism. Antigens, Differentiation, Myelomonocytic / metabolism. Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Combined Modality Therapy. Fatal Outcome. Hematopoietic Stem Cell Transplantation. Humans. Male. Remission Induction. Sialic Acid Binding Ig-like Lectin 3

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  • (PMID = 18668307.001).
  • [ISSN] 0925-5710
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Aminoglycosides; 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antigens, CD; 0 / Antigens, Differentiation, Myelomonocytic; 0 / Antineoplastic Agents; 0 / CD33 protein, human; 0 / Sialic Acid Binding Ig-like Lectin 3; 0 / gemtuzumab
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83. Guo Y, Köck K, Ritter CA, Chen ZS, Grube M, Jedlitschky G, Illmer T, Ayres M, Beck JF, Siegmund W, Ehninger G, Gandhi V, Kroemer HK, Kruh GD, Schaich M: Expression of ABCC-type nucleotide exporters in blasts of adult acute myeloid leukemia: relation to long-term survival. Clin Cancer Res; 2009 Mar 1;15(5):1762-9
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  • [Title] Expression of ABCC-type nucleotide exporters in blasts of adult acute myeloid leukemia: relation to long-term survival.
  • PURPOSE: Successful treatment of acute myeloid leukemia (AML) remains a therapeutic challenge, with a high percentage of patients suffering from persistent or relapsed disease.
  • The nucleoside analogue cytosine arabinoside (AraC) is administered to all patients with AML.
  • EXPERIMENTAL DESIGN: Expression of ABCC transporters MRP4, MRP5, and MRP8 in blast samples from 50 AML patients was investigated by real-time reverse transcription-PCR analysis and correlated with clinical outcome measures.
  • CONCLUSION: These data suggest that MRP8 is differentially expressed in AML blasts, that expression of MRP8 serves as a predictive marker for treatment outcome in AML, and that efflux of AraC metabolites by MRP8 is a mechanism that contributes to resistance of AML blasts.
  • [MeSH-major] ATP-Binding Cassette Transporters / metabolism. Blast Crisis. Leukemia, Myeloid, Acute / metabolism. Leukemia, Myeloid, Acute / pathology. Multidrug Resistance-Associated Proteins / metabolism
  • [MeSH-minor] Adult. Aged. Cell Membrane / metabolism. Cytarabine / metabolism. Drug Resistance, Neoplasm. Female. Humans. LLC-PK1 Cells. Male. Middle Aged. Prognosis. RNA, Messenger / genetics. RNA, Messenger / metabolism. Reverse Transcriptase Polymerase Chain Reaction. Stem Cells / metabolism. Stem Cells / pathology. Survival Rate

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  • (PMID = 19240178.001).
  • [ISSN] 1078-0432
  • [Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research
  • [ISO-abbreviation] Clin. Cancer Res.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA113474; United States / NCI NIH HHS / CA / CA57629; United States / NCI NIH HHS / CA / CA73728
  • [Publication-type] Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / ABCC11 protein, human; 0 / ABCC4 protein, human; 0 / ABCC5 protein, human; 0 / Multidrug Resistance-Associated Proteins; 0 / RNA, Messenger; 04079A1RDZ / Cytarabine
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84. Ciurea SO, Saliba R, Rondon G, Pesoa S, Cano P, Fernandez-Vina M, Qureshi S, Worth LL, McMannis J, Kebriaei P, Jones RB, Korbling M, Qazilbash M, Shpall EJ, Giralt S, de Lima M, Champlin RE, Gajewski J: Reduced-intensity conditioning using fludarabine, melphalan and thiotepa for adult patients undergoing haploidentical SCT. Bone Marrow Transplant; 2010 Mar;45(3):429-36
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  • [Title] Reduced-intensity conditioning using fludarabine, melphalan and thiotepa for adult patients undergoing haploidentical SCT.
  • A total of 21 out of 22 patients with AML/myelodysplastic syndrome (MDS) achieved remission after transplant (16 with relapsed/refractory AML).
  • Five out of the 12 patients (42%) with AML/MDS with <15% BM blasts survived long term as compared with none with more advanced disease (P=0.03).
  • HaploSCT with this fludarabine, melphalan and thiotepa and ATG RIC is an effective, well-tolerated conditioning regimen for patients with AML/MDS with low disease burden at the time of transplant and allowed a high rate of engraftment in patients without DSA.
  • [MeSH-minor] Adolescent. Adult. Antilymphocyte Serum / administration & dosage. Child. Female. Hematologic Neoplasms / therapy. Humans. Infection / etiology. Leukemia, Myeloid, Acute / therapy. Male. Melphalan / administration & dosage. Middle Aged. Myelodysplastic Syndromes / therapy. Survival Rate. T-Lymphocytes / immunology. Thiotepa / administration & dosage. Transplantation, Homologous. Treatment Outcome. Vidarabine / administration & dosage. Vidarabine / analogs & derivatives. Young Adult

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  • (PMID = 19668237.001).
  • [ISSN] 1476-5365
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / P01 CA055164
  • [Publication-type] Clinical Trial, Phase II; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antilymphocyte Serum; 0 / Myeloablative Agonists; 905Z5W3GKH / Thiotepa; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine; Q41OR9510P / Melphalan
  • [Other-IDs] NLM/ NIHMS598753; NLM/ PMC4080627
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85. Wrzesień-Kuś A, Robak T, Wierzbowska A, Lech-Marańda E, Pluta A, Wawrzyniak E, Krawczyńska A, Kuliczkowski K, Mazur G, Kiebiński M, Dmoszyńska A, Wach M, Hellmann A, Baran W, Hołowiecki J, Kyrcz-Krzemień S, Grosicki S, Polish Adult Leukemia Group: A multicenter, open, noncomparative, phase II study of the combination of cladribine (2-chlorodeoxyadenosine), cytarabine, granulocyte colony-stimulating factor and mitoxantrone as induction therapy in refractory acute myeloid leukemia: a report of the Polish Adult Leukemia Group. Ann Hematol; 2005 Sep;84(9):557-64
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  • [Title] A multicenter, open, noncomparative, phase II study of the combination of cladribine (2-chlorodeoxyadenosine), cytarabine, granulocyte colony-stimulating factor and mitoxantrone as induction therapy in refractory acute myeloid leukemia: a report of the Polish Adult Leukemia Group.
  • Purine nucleoside analogues, cladribine (2-chlorodeoxyadenosine, 2-CdA) and fludarabine (FAMP) are active agents in acute myeloid leukemias (AMLs).
  • The current multicenter phase II study was initiated to evaluate the efficacy and toxicity of induction treatment consisting of 2-CdA (5 mg/m2), Ara-C (2 g/m2), mitoxantrone (MIT, 10 mg/m2) and granulocyte colony-stimulating factor (G-CSF) (CLAG-M) in refractory AML.
  • Forty-three patients from five centers were registered: 25 primary resistant and 18 relapsed.
  • We conclude that CLAG-M regimen has significant antileukemia activity in refractory AML, which seems to be better than the activity of many other regimens.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid / drug therapy
  • [MeSH-minor] Acute Disease. Adult. Aged. Cladribine / administration & dosage. Cytarabine / administration & dosage. Drug Therapy, Combination. Female. Granulocyte Colony-Stimulating Factor / administration & dosage. Hematologic Diseases / chemically induced. Hematopoietic Stem Cell Transplantation. Humans. Male. Middle Aged. Mitoxantrone / administration & dosage. Remission Induction / methods. Salvage Therapy / methods. Survival Analysis

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  • (PMID = 15856358.001).
  • [ISSN] 0939-5555
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article; Multicenter Study
  • [Publication-country] Germany
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 47M74X9YT5 / Cladribine; BZ114NVM5P / Mitoxantrone; CLAG protocol
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86. Fazlina N, Maha A, Jamal R, Zarina AL, Cheong SK, Hamidah H, Ainoon O, Zulkifli SZ, Hamidah NH: Expression of multidrug resistance (MDR) proteins and in vitro drug resistance in acute leukemias. Hematology; 2007 Feb;12(1):33-7
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  • [Title] Expression of multidrug resistance (MDR) proteins and in vitro drug resistance in acute leukemias.
  • The expression of the multidrug resistance (MDR) proteins may influence the outcome of treatment in patients with acute leukemia.
  • A total of 82 newly diagnosed acute leukemia cases (43 adult myeloid leukaemia, AML cases and 39 acute lymphoblastic leukaemia, ALL cases) and 16 relapsed cases (8 AML cases and 8 ALL cases) were studied.
  • In newly diagnosed cases, we found that childhood ALL samples showed higher IC50 values of dnr (0.040 +/- 2.320) compared to adult AML samples (0.021 +/- 0.158).
  • In contrast, newly diagnosed adult AML samples showed higher IC50 values of ara-C (0.157 +/- 0.529) compared to childhood ALL samples (0.100 +/- 2.350).
  • In relapsed cases, two samples of childhood ALL showed IC50 values of dnr (0.910 +/- 1.760) and ara-C (1.310 +/- 2.390), which was higher compared to childhood AML samples (0.129 +/- 0.214 and 0.210 +/- 0.003, respectively).
  • In conclusion, we found that MTS assay is an easy, rapid and non laborious method to study in vitro drug resistance in acute leukaemia cases.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Drug Resistance, Multiple. Drug Resistance, Neoplasm. Leukemia / metabolism. Neoplasm Proteins / metabolism. P-Glycoproteins / metabolism
  • [MeSH-minor] Acute Disease. Adolescent. Adult. Age Factors. Aged. Aged, 80 and over. Cell Survival. Child. Child, Preschool. Coloring Agents / analysis. Cytarabine / pharmacology. Daunorubicin / pharmacology. Female. Humans. Infant. Inhibitory Concentration 50. Leukemia, Myeloid / drug therapy. Leukemia, Myeloid / metabolism. Male. Methylphenazonium Methosulfate / pharmacology. Middle Aged. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism. Recurrence. Staining and Labeling / methods. Tetrazolium Salts / analysis. Thiazoles / analysis. Treatment Outcome. Tumor Cells, Cultured / drug effects. Tumor Cells, Cultured / ultrastructure

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  • (PMID = 17364990.001).
  • [ISSN] 1607-8454
  • [Journal-full-title] Hematology (Amsterdam, Netherlands)
  • [ISO-abbreviation] Hematology
  • [Language] eng
  • [Publication-type] Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Coloring Agents; 0 / Neoplasm Proteins; 0 / P-Glycoproteins; 0 / Tetrazolium Salts; 0 / Thiazoles; 04079A1RDZ / Cytarabine; 138169-43-4 / 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; 299-11-6 / Methylphenazonium Methosulfate; ZS7284E0ZP / Daunorubicin
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87. Allen SL, Kolitz JE, Lundberg AS, Bennett JM, Capizzi RL, Budman DR: Phase I trials of amonafide as monotherapy and in combination with cytarabine in patients with poor-risk acute myeloid leukemia. Leuk Res; 2010 Apr;34(4):487-91
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  • [Title] Phase I trials of amonafide as monotherapy and in combination with cytarabine in patients with poor-risk acute myeloid leukemia.
  • Amonafide-l-malate (amonafide) is a unique DNA intercalator that maintains activity in the presence of MDR mechanisms, a frequent cause of treatment-failure in secondary AML.
  • 43 patients with relapsed/refractory or secondary AML or CML blast crisis were enrolled into two phase I dose-escalation studies investigating amonafide as monotherapy or in combination with cytarabine.
  • Between both trials responses occurred in 9/20 patients with secondary AML.
  • Both trials demonstrated an acceptable safety profile and significant antileukemic activity in patients with poor-risk AML, especially those with secondary AML.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cytarabine / administration & dosage. Leukemia, Myeloid, Acute / drug therapy. Naphthalimides / administration & dosage
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Female. Humans. Male. Middle Aged. Remission Induction. Risk Factors. Treatment Outcome. Young Adult

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  • [Copyright] Copyright (c) 2009 Elsevier Ltd. All rights reserved.
  • (PMID = 19748672.001).
  • [ISSN] 1873-5835
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Naphthalimides; 04079A1RDZ / Cytarabine; 1Q8D39N37L / amonafide
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88. Tang JM, Meng FY, Ma WL: [Evolution of gene expression profile in 3 cases of acute myeloid leukemia]. Zhonghua Xue Ye Xue Za Zhi; 2005 Nov;26(11):653-5
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  • [Title] [Evolution of gene expression profile in 3 cases of acute myeloid leukemia].
  • OBJECTIVE: To investigate the mechanism of refractoriness of acute myeloid leukemia (AML) by studying the changes of gene mRNA expression from primary diagnosis to relapsed disease in AML.
  • METHODS: Differences in gene expression profile of bone marrow mononuclear cells were compared between primary diagnosis and relapsed/refractory disease in 3 patients with M(2a) subtype of AML using Agilent human 1B 60mer oligonucleotide microarray.
  • RESULTS: Common alterations were found in 10 genes among the 20173 genes tested at relapsed/refractory disease as compared with that at primary diagnosis in 3 patients.
  • CONCLUSION: Development of relapsed/refractory disease in AML-M(2a) might be associated with the mRNA expression changes in the 10 genes tested including DAPK1.
  • The alteration of these genes may be indications for the early diagnosis of refractoriness of AML, and these genes might provide new therapeutic targets for the treatment of refractory AML.
  • [MeSH-major] Gene Expression Profiling. Leukemia, Myeloid, Acute / genetics
  • [MeSH-minor] Adult. Female. Gene Expression Regulation, Leukemic. Humans. Male. Middle Aged. Oligonucleotide Array Sequence Analysis

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  • (PMID = 16620549.001).
  • [ISSN] 0253-2727
  • [Journal-full-title] Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi
  • [ISO-abbreviation] Zhonghua Xue Ye Xue Za Zhi
  • [Language] chi
  • [Publication-type] Case Reports; English Abstract; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] China
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89. Szotkowski T, Muzik J, Voglova J, Koza V, Maaloufova J, Kozak T, Jarosova M, Michalova K, Zak P, Steinerova K, Vydra J, Lanska M, Katrincsakova B, Sicova K, Pavlik T, Dusek L, Indrak K: Prognostic factors and treatment outcome in 1,516 adult patients with de novo and secondary acute myeloid leukemia in 1999-2009 in 5 hematology intensive care centers in the Czech Republic. Neoplasma; 2010;57(6):578-89
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  • [Title] Prognostic factors and treatment outcome in 1,516 adult patients with de novo and secondary acute myeloid leukemia in 1999-2009 in 5 hematology intensive care centers in the Czech Republic.
  • Acute myeloid leukemia (AML) is a severe condition with a high mortality.
  • The study represents a detailed analysis of the role of these factors and treatment outcomes based on a long-term follow-up of patients treated in 5 hematology intensive care centers in the Czech Republic.The studied group comprised 1,188 patients with de novo AML and 328 patients with secondary AML.
  • Curatively treated patients achieved fewer complete remissions and relapsed more often than those with de novo AML.
  • Patients with secondary AML had lower rates of allogeneic transplantation as part of consolidation therapy and a significantly shorter median overall survival.
  • However, the treatment outcome of de novo AML patients is not satisfactory, the only exception being those with acute promyelocytic leukemia.
  • [MeSH-major] Leukemia, Myeloid, Acute / mortality. Neoplasms, Second Primary / mortality
  • [MeSH-minor] Adult. Age Factors. Aged. Aged, 80 and over. Chromosome Aberrations. Female. Hematopoietic Stem Cell Transplantation. Humans. Leukocyte Count. Male. Middle Aged. Prognosis. Time Factors. Treatment Outcome


90. Zhang Y, Zhang SJ, Qiu HX, Qiao C, Sun HM, Li JY: [Analysis of CEBPA mutation in acute myeloid leukemia]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2010 Aug;18(4):859-62
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  • [Title] [Analysis of CEBPA mutation in acute myeloid leukemia].
  • In order to evaluate the incidence of CCAAT/enhancer binding protein alpha (cebpa) gene mutation in patients with acute myeloid leukemia (AML), 22 AML patients with normal karyotype (NK-AML) were enrolled in this study, including de novo AML and relapsed AML.
  • The results showed that the cebpa mutations including deletion and insertion were found in 4 out of 22 AML patients (18.2%) and all of these 4 patients were M(2).
  • It is concluded that PCR combined with direct sequencing and clone sequencing can be used to detect cebpa mutations. cebpa mutations are mainly identified in M(2) subtype of NK-AML patients, its significance for prognosis needs to further investigate.

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  • (PMID = 20723288.001).
  • [ISSN] 1009-2137
  • [Journal-full-title] Zhongguo shi yan xue ye xue za zhi
  • [ISO-abbreviation] Zhongguo Shi Yan Xue Ye Xue Za Zhi
  • [Language] CHI
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 0 / CCAAT-Enhancer-Binding Protein-alpha
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91. Zou XL, Liu T, Meng WT, Huang XO: [Expression of tumor suppressor gene pten in patients with myelodysplastic syndrome and acute myeloid leukemia]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2008 Oct;16(5):1086-90
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  • [Title] [Expression of tumor suppressor gene pten in patients with myelodysplastic syndrome and acute myeloid leukemia].
  • To study the expression and significance of pten gene in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), RT-PCR and Western blot were respectively applied to detect pten mRNA and PTEN protein in Jurkat cells (as negative control), in bone marrow nucleated cells of 35 patients with MDS, 45 patients with AML and 20 normal control.
  • The results showed that pten mRNA expression could not be detected in Jurkat cells, and the positive rate in MDS patients (77.1%) was significantly lower than that in normal control group (90.0%) (p > 0.05), while significant difference was found between AML patients and normal control (60.0% vs 90.0%, p < 0.05); the positive rate in MDS-RAEB patients (70.0%) was lower than that in MDS-RCMD (86.7%); positive rate in de novo and relapsed AML patients (53.3%) was lower than that in AML patients in CR (73.3%), but statistics tests did not show significant difference (p > 0.05).
  • The results of relative expression level of pten mRNA in all groups indicated that both relative expression levels in MDS patients and AML patients were definitely lower than that in normal control group (p < 0.005); the relative expression level in MDS-RAEB patients was lower than that in MDS-RCMD patients (p < 0.05); and in de novo and relapsed AML patients was obviously lower than that in AML patients in CR (p < 0.001).
  • However, there was no significant difference between MDS and AML patients (p > 0.05).
  • The positive rate of PTEN protein expression in both MDS (65.7%) and AML (54.8%) patients were lower than that in normal control (90.0%) (p < 0.05), and there was no significant difference when comparing MDS-RCMD patients (80.0%) with MDS-RAEB patients (55.0%) (p > 0.05), but positive rate of PTEN protein expression in de novo and relapsed AML patients (44.4%) was significantly lower than that in AML patients in CR (73.3%) (p < 0.05).
  • It is concluded that the complete loss of pten mRNA in MDS and AML is uncommon, but the relative expression level in both diseases is significantly lower than that in normal people.
  • The positive rates of PTEN protein expression in both MDS and AML patients are lower, compared with normal people, but are not in accordance with the expression of pten mRNA.
  • The abnormalities of pten gene expression may be involved in the pathogenesis of MDS and AML.


92. Hoshino T, Matsushima T, Saitoh Y, Yamane A, Takizawa M, Irisawa H, Saitoh T, Handa H, Tsukamoto N, Karasawa M, Murakami H, Nojima Y: Sacroiliitis as an initial manifestation of acute myelogenous leukemia. Int J Hematol; 2006 Dec;84(5):421-4
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  • [Title] Sacroiliitis as an initial manifestation of acute myelogenous leukemia.
  • We herein report a 28-year-old female patient who presented with sacroiliitis as an initial manifestation of acute myelogenous leukemia (AML).
  • Although she was initially diagnosed with myelodysplastic syndrome (MDS), blasts rapidly increased and AML developed 1 month after the diagnosis of MDS with Sacroiliitis.
  • Induction chemotherapy failed to induce a complete remission of AML, but it did effectively treat the sacroiliitis.
  • However, the sacroiliitis relapsed when the leukemia cells progressed thereafter.
  • The close relationship between the occurrence of sacroiliitis and AML suggested that autoimmune sacroiliitis was a paraneoplastic phenomenon of AML in this patient.
  • Although autoimmune disorders develop in a substantial number of MDS patients, they are rarely observed in de novo AML.
  • No previous report has described sacroiliitis as the initial manifestation of de novo AML.
  • [MeSH-major] Leukemia, Myeloid, Acute. Sacroiliac Joint. Spondylitis, Ankylosing
  • [MeSH-minor] Adrenal Cortex Hormones / therapeutic use. Adult. Blast Crisis / diagnosis. Blast Crisis / radiography. Blast Crisis / therapy. Bone Marrow Transplantation. Fatal Outcome. Female. Humans. Recurrence. Transplantation, Homologous


93. Sakamaki H: [The role of gemtuzumab ozogamicin in the treatment of acute myeloid leukemia patients]. Gan To Kagaku Ryoho; 2008 Sep;35(9):1629-34
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  • [Title] [The role of gemtuzumab ozogamicin in the treatment of acute myeloid leukemia patients].
  • Gemtuzumab Ozogamicin (GO) targets leukemia cells expressing CD33 by means of a monoclonal antibody conjugated to a cytotoxic agent, calicheamicin.
  • GO has been approved in Japan as monotherapy for the treatment of patients with relapsed/refractory acute myeloid leukemia (AML)since 2005.
  • GO administered as a single agent has resulted in overall response rates of about 30% in previously relapsed adult AML.
  • Although caution is advised when administering GO within 115 days of a stem cell transplantation (SCT) procedure because of veno-occlusive disease, recent clinical studies overseas suggest that GO can be integrated into reduced-intensity conditioning therapy before allogeneic SCT in patients with relapsed AML.
  • [MeSH-major] Aminoglycosides / immunology. Aminoglycosides / therapeutic use. Antibodies, Monoclonal / immunology. Antibodies, Monoclonal / therapeutic use. Antineoplastic Agents / immunology. Antineoplastic Agents / therapeutic use. Leukemia, Myeloid, Acute / drug therapy. Leukemia, Myeloid, Acute / immunology

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  • (PMID = 18799927.001).
  • [ISSN] 0385-0684
  • [Journal-full-title] Gan to kagaku ryoho. Cancer & chemotherapy
  • [ISO-abbreviation] Gan To Kagaku Ryoho
  • [Language] jpn
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Aminoglycosides; 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antineoplastic Agents; 0 / gemtuzumab
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94. Khanim FL, Hayden RE, Birtwistle J, Lodi A, Tiziani S, Davies NJ, Ride JP, Viant MR, Gunther UL, Mountford JC, Schrewe H, Green RM, Murray JA, Drayson MT, Bunce CM: Combined bezafibrate and medroxyprogesterone acetate: potential novel therapy for acute myeloid leukaemia. PLoS One; 2009;4(12):e8147
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  • [Title] Combined bezafibrate and medroxyprogesterone acetate: potential novel therapy for acute myeloid leukaemia.
  • BACKGROUND: The majority of acute myeloid leukaemia (AML) patients are over sixty years of age.
  • PRINCIPAL FINDINGS: Here we demonstrate the potent anti-leukaemic activity of the combination of the lipid-regulating drug bezafibrate (BEZ) and the sex hormone medroxyprogesterone acetate (MPA) against AML cell lines and primary AML cells.
  • B/M treatment resulted in growth arrest, apoptosis and cell differentiation in both AML cell lines and primary AML cells and these actions were recapitulated by treatment with 15d-PGJ(2).
  • Importantly, the actions of B/M had little effect on the survival of normal adult myeloid progenitors.
  • SIGNIFICANCE: Collectively our data demonstrate that B/M treatment of AML cells elevated ROS and delivered the anti-neoplastic actions of 15d-PGJ(2).
  • These observations provide the mechanistic rationale for the redeployment of B/M in elderly and relapsed AML.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Bezafibrate / therapeutic use. Leukemia, Myeloid, Acute / drug therapy. Medroxyprogesterone Acetate / therapeutic use

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  • (PMID = 19997560.001).
  • [ISSN] 1932-6203
  • [Journal-full-title] PloS one
  • [ISO-abbreviation] PLoS ONE
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / 15-deoxyprostaglandin J2; 0 / Antigens, CD34; 0 / I-kappa B Proteins; 0 / PPAR gamma; 0 / Reactive Oxygen Species; 11103-57-4 / Vitamin A; 1C6V77QF41 / Cholecalciferol; C2QI4IOI2G / Medroxyprogesterone Acetate; EC 1.1.- / 3-Hydroxysteroid Dehydrogenases; EC 1.1.1.- / AKR1C3 protein, human; EC 1.1.1.- / Hydroxyprostaglandin Dehydrogenases; GAN16C9B8O / Glutathione; RXY07S6CZ2 / Prostaglandin D2; Y9449Q51XH / Bezafibrate
  • [Other-IDs] NLM/ PMC2785482
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95. Zhong LY, Li QH, Huang ZL, Lin W, Lu ZS, Weng JY, Wu SJ, Du X: Regimen containing perarubicin for the treatment of newly diagnosed young patients with acute myeloid leukemia. Ai Zheng; 2009 Jun;28(6):619-25
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  • [Title] Regimen containing perarubicin for the treatment of newly diagnosed young patients with acute myeloid leukemia.
  • BACKGROUND AND OBJECTIVE: Chemotherapy regimen containing anthracyclines has been used as the standard treatment for acute myeloid leukemia (AML).
  • This study was to compare the efficacy and toxicity of the chemotherapy regimen containing perarubicin (THP) with that containing mitoxantrone (MIT) for young patients with newly diagnosed AML.
  • METHODS: A total of 129 patients with newly diagnosed AML, aged 16 to 60 years olds, were assigned for induction chemotherapy containing one to two courses with standard-dose cytarabine (Ara-C) and an anthracycline antibiotic, THP or MIT.
  • Nine (34.61%) and 11 (22.92%) out of CR patients treated by THP and MIT, respectively, relapsed within one year (P=0.28).
  • CONCLUSIONS: Regimen containing THP plus Ara-C can be used for young adults with newly diagnosed AML for remission induction, but it is not superior to the regimen with MIT.
  • Consolidation chemotherapy with THP or MIT is feasible for young adults with AML after CR.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Doxorubicin / analogs & derivatives. Leukemia, Myeloid, Acute / drug therapy
  • [MeSH-minor] Adolescent. Adult. Agranulocytosis / chemically induced. Alopecia / chemically induced. Cytarabine / administration & dosage. Female. Humans. Male. Middle Aged. Mitoxantrone / administration & dosage. Nausea / chemically induced. Recurrence. Remission Induction. Young Adult

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  • (PMID = 19635200.001).
  • [Journal-full-title] Ai zheng = Aizheng = Chinese journal of cancer
  • [ISO-abbreviation] Ai Zheng
  • [Language] eng
  • [Publication-type] Clinical Trial; Comparative Study; Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 80168379AG / Doxorubicin; BZ114NVM5P / Mitoxantrone; D58G680W0G / pirarubicin
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96. Whitman SP, Ruppert AS, Marcucci G, Mrózek K, Paschka P, Langer C, Baldus CD, Wen J, Vukosavljevic T, Powell BL, Carroll AJ, Kolitz JE, Larson RA, Caligiuri MA, Bloomfield CD: Long-term disease-free survivors with cytogenetically normal acute myeloid leukemia and MLL partial tandem duplication: a Cancer and Leukemia Group B study. Blood; 2007 Jun 15;109(12):5164-7
ClinicalTrials.gov. clinical trials - ClinicalTrials.gov .

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  • [Title] Long-term disease-free survivors with cytogenetically normal acute myeloid leukemia and MLL partial tandem duplication: a Cancer and Leukemia Group B study.
  • The clinical impact of MLL partial tandem duplication (MLL-PTD) was evaluated in 238 adults aged 18 to 59 years with cytogenetically normal (CN) de novo acute myeloid leukemia (AML) who were treated intensively on similar Cancer and Leukemia Group B protocols 9621 and 19808.
  • Thirteen MLL-PTD(+) patients relapsed within 1.4 years of achieving CR.
  • MLL-PTD(+) patients who relapsed more often had other adverse CN-AML-associated molecular markers.
  • Intensive consolidation therapy that included autologous peripheral stem-cell transplantation during CR1 may have contributed to the better outcome of this historically poor-prognosis group of CN-AML patients with MLL-PTD.

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  • (PMID = 17341662.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R01 CA102031; United States / NCI NIH HHS / CA / CA16058; United States / NCI NIH HHS / CA / CA102031; United States / NCI NIH HHS / CA / CA101140; United States / NCI NIH HHS / CA / U10 CA077658; United States / NCI NIH HHS / CA / CA098933; United States / NCI NIH HHS / CA / CA089341; United States / NCI NIH HHS / CA / CA41287; United States / NCI NIH HHS / CA / R01 CA089341; United States / NCI NIH HHS / CA / U10 CA101140; United States / NCI NIH HHS / CA / U10 CA041287; United States / NCI NIH HHS / CA / R01 CA098933; United States / NCI NIH HHS / CA / K01 CA096887; United States / NCI NIH HHS / CA / P30 CA016058; United States / NCI NIH HHS / CA / CA77658; United States / NCI NIH HHS / CA / CA096887
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / MLL protein, human; 149025-06-9 / Myeloid-Lymphoid Leukemia Protein; EC 2.1.1.43 / Histone-Lysine N-Methyltransferase
  • [Other-IDs] NLM/ PMC1890839
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97. Abd El-Ghaffar HA, Aladle DA, Farahat SE, Abd El-Hady N: P-glycoprotein (P-170) expression in acute leukemias. Hematology; 2006 Feb;11(1):35-41
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  • [Title] P-glycoprotein (P-170) expression in acute leukemias.
  • Multidrug resistance (MDR) is still a major obstacle to chemotherapy success in acute myeloid leukemia (AML) and to a less extent acute lymphoblastic leukemia (ALL).
  • This study was planned to study the expression of P-glycoprotein/170 in patients with acute leukemia and the effect of Cyclosporin A (CSA) as a modulator of P-glycoprotein functional activity.
  • The study was carried out on 20 patients with acute leukemia (14 AML cases and 6 ALL cases).
  • Flow cytometric analysis of P-gp/170 surface expression was performed using UIC-2 MoAb together with the functional assay using Rhodamine 123 (Rh 123) and Cyclosporin A as a modulator.P-gp/170 was expressed on the leukemic cells of 37.5% of relapsed patients (40.0% of AML and 33.3% of ALL cases), whereas 27.2% of de novo patients expressed P-gp/170 (33.3% of AML cases and 0% of ALL cases).
  • The functional activity of MDR-1 gp was 71.4% in AML and 33.3% in ALL patients compared with16.6% in normal lymphocytes.
  • From this study, it is clear that P-gp/170 is expressed to a higher degree in leukemic cells and this is greater in relapsed compared to de novo cases and more in AML than ALL blasts.
  • [MeSH-major] Drug Resistance, Multiple. Drug Resistance, Neoplasm. Gene Expression Regulation, Leukemic. Leukemia, Myeloid, Acute / metabolism. P-Glycoprotein / metabolism. Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • [MeSH-minor] Adolescent. Adult. Child. Child, Preschool. Female. Flow Cytometry / methods. Humans. Male. Middle Aged

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  • (PMID = 16522547.001).
  • [ISSN] 1024-5332
  • [Journal-full-title] Hematology (Amsterdam, Netherlands)
  • [ISO-abbreviation] Hematology
  • [Language] eng
  • [Publication-type] Clinical Trial; Comparative Study; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / P-Glycoprotein
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98. Martin MG, Augustin KM, Uy GL, Welch JS, Hladnik L, Goyal S, Tiwari D, Monahan RS, Reichley RM, Cashen AF, Stockerl-Goldstein K, Westervelt P, Abboud CN, Dipersio JF, Vij R: Salvage therapy for acute myeloid leukemia with fludarabine, cytarabine, and idarubicin with or without gemtuzumab ozogamicin and with concurrent or sequential G-CSF. Am J Hematol; 2009 Nov;84(11):733-7
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  • [Title] Salvage therapy for acute myeloid leukemia with fludarabine, cytarabine, and idarubicin with or without gemtuzumab ozogamicin and with concurrent or sequential G-CSF.
  • The current salvage therapies for relapsed/refractory acute myeloid leukemia (AML) are unsatisfactory.
  • Over the past 7 years, we have used two salvage regimens: fludarabine, cytarabine, and idarubicin with (FLAG-IM) or without gemtuzumab ozogamicin (GO) (9 mg/m(2) on Day 8) (FLAG-I) in relapsed/refractory AML.
  • The addition of GO, at this dose and schedule, to FLAG-I failed to improve the outcomes in patients with relapsed/refractory AML.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Granulocyte Colony-Stimulating Factor / administration & dosage. Leukemia, Myeloid, Acute / drug therapy. Salvage Therapy / methods
  • [MeSH-minor] Adolescent. Adult. Aged. Aminoglycosides / administration & dosage. Antibodies, Monoclonal / administration & dosage. Antibodies, Monoclonal, Humanized. Cytarabine / administration & dosage. Drug Evaluation. Female. Humans. Idarubicin / administration & dosage. Male. Middle Aged. Remission Induction. Retrospective Studies. Survival Analysis. Treatment Outcome. Vidarabine / administration & dosage. Vidarabine / analogs & derivatives. Young Adult

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  • (PMID = 19806665.001).
  • [ISSN] 1096-8652
  • [Journal-full-title] American journal of hematology
  • [ISO-abbreviation] Am. J. Hematol.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Aminoglycosides; 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / gemtuzumab; 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine; ZRP63D75JW / Idarubicin
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99. Grigg AP, Gibson J, Bardy PG, Reynolds J, Shuttleworth P, Koelmeyer RL, Szer J, Roberts AW, To LB, Kennedy G, Bradstock KF: A prospective multicenter trial of peripheral blood stem cell sibling allografts for acute myeloid leukemia in first complete remission using fludarabine-cyclophosphamide reduced intensity conditioning. Biol Blood Marrow Transplant; 2007 May;13(5):560-7
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  • [Title] A prospective multicenter trial of peripheral blood stem cell sibling allografts for acute myeloid leukemia in first complete remission using fludarabine-cyclophosphamide reduced intensity conditioning.
  • The role of allogeneic transplantation in patients with de novo acute myeloid leukemia in first complete remission (AML-CR1) is controversial.
  • Aiming to preserve a graft-versus-leukemia effect, but minimize morbidity and mortality from conditioning-related toxicity and graft-versus-host disease (GVHD), we conducted a prospective multicenter study of reduced-intensity conditioning (RIC) as preparation for peripheral blood stem cell sibling allografts in patients with intermediate or poor risk AML-CR1.
  • The overall incidence of grade II-IV acute GVHD was low (21%), but the 3 patients (9%) who developed grade IV GVHD died.
  • Donor T cell chimerism was rapid and generally complete, but complete myeloid chimerism was delayed.
  • Thirteen patients (38%) relapsed, 12 within a year of transplant.
  • These observations justify a prospective comparison of RIC versus myeloablative conditioning allografts for AML-CR1.
  • [MeSH-major] Acute Disease / therapy. Hematopoietic Stem Cell Transplantation / methods. Leukemia, Myeloid / therapy. Peripheral Blood Stem Cell Transplantation / methods. Transplantation Conditioning / methods
  • [MeSH-minor] Adult. Chimerism. Cyclophosphamide / therapeutic use. Disease-Free Survival. Female. Fertility. Graft vs Host Disease. Humans. Kaplan-Meier Estimate. Karnofsky Performance Status. Male. Middle Aged. Prospective Studies. Transplantation, Homologous / methods. Vidarabine / analogs & derivatives. Vidarabine / therapeutic use

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  • (PMID = 17448915.001).
  • [ISSN] 1083-8791
  • [Journal-full-title] Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • [ISO-abbreviation] Biol. Blood Marrow Transplant.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Multicenter Study
  • [Publication-country] United States
  • [Chemical-registry-number] 8N3DW7272P / Cyclophosphamide; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine
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100. Matondo M, Bousquet-Dubouch MP, Gallay N, Uttenweiler-Joseph S, Recher C, Payrastre B, Manenti S, Monsarrat B, Burlet-Schiltz O: Proteasome inhibitor-induced apoptosis in acute myeloid leukemia: a correlation with the proteasome status. Leuk Res; 2010 Apr;34(4):498-506
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  • [Title] Proteasome inhibitor-induced apoptosis in acute myeloid leukemia: a correlation with the proteasome status.
  • The proteasome inhibitor bortezomib has recently been approved for the treatment of relapsed and refractory multiple myeloma.
  • In this study, we investigated the induction of apoptosis by proteasome inhibitors in several human acute myeloid leukemia (AML) cell lines and in primary cells from patients.
  • We demonstrate that these drugs induce a high level of apoptosis in the KG1a cell line, in which the therapeutic drug daunorubicin is poorly active, compared to other AML cell lines.
  • Moreover, the level of 20S proteasome in KG1a cells was also high compared to other AML cell lines, suggesting a relationship between the high sensitivity to proteasome inhibitors and an elevated amount of 20S proteasome.
  • Altogether, our results suggest that various AML subtypes may present different responses to proteasome inhibitors, that these molecules can be potentially considered as interesting therapeutic alternatives for these pathologies, and that the amount of 20S proteasome in AML cells may be predictive of the cellular response to these inhibitors.
  • [MeSH-major] Apoptosis / drug effects. Leukemia, Myeloid, Acute / pathology. Protease Inhibitors / pharmacology. Proteasome Endopeptidase Complex / metabolism. Proteasome Inhibitors
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Antineoplastic Agents / pharmacology. Boronic Acids / pharmacology. Bortezomib. Daunorubicin / pharmacology. Drug Resistance, Neoplasm / drug effects. Drug Resistance, Neoplasm / physiology. Female. HL-60 Cells. Humans. Leupeptins / pharmacology. Male. Middle Aged. Prognosis. Pyrazines / pharmacology. Tumor Cells, Cultured. U937 Cells

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  • [Copyright] Copyright (c) 2009 Elsevier Ltd. All rights reserved.
  • [CommentIn] Leuk Res. 2010 Apr;34(4):411-2 [19819547.001]
  • (PMID = 19811823.001).
  • [ISSN] 1873-5835
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Boronic Acids; 0 / Leupeptins; 0 / Protease Inhibitors; 0 / Proteasome Inhibitors; 0 / Pyrazines; 133407-82-6 / benzyloxycarbonylleucyl-leucyl-leucine aldehyde; 69G8BD63PP / Bortezomib; EC 3.4.25.1 / Proteasome Endopeptidase Complex; ZS7284E0ZP / Daunorubicin
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