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1. Bacher U, Haferlach T, Alpermann T, Zenger M, Kröger N, Beelen DW, Kern W, Schnittger S, Haferlach C: Comparison of cytogenetic clonal evolution patterns following allogeneic hematopoietic transplantation versus conventional treatment in patients at relapse of AML. Biol Blood Marrow Transplant; 2010 Dec;16(12):1649-57
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  • [Title] Comparison of cytogenetic clonal evolution patterns following allogeneic hematopoietic transplantation versus conventional treatment in patients at relapse of AML.
  • Relapse of acute myelogenous leukemia has been associated with clonal cytogenetic evolution, but no study focused specifically on relapse after allogeneic hematopoietic stem cell transplantation (HSCT).
  • We compared karyotypes in 160 patients at both diagnosis and relapse either after allo-HSCT (n = 26) or standard chemotherapy (n = 134) using chromosome banding analysis combined with fluorescein in situ hybridization.
  • At diagnosis, aberrant karyotypes were more frequent in the HSCT than in the chemotherapy cohort (16 of 26; 61.5% versus 63 of 134; 47.0%).
  • Differences in the karyotypes between diagnosis and relapse were more frequent in the allo-cohort (14 of 26; 53.8% versus 49 of 134; 36.6%) than in the conventional cohort (n.s.
  • The mean number of cytogenetic alterations per patient was increasing from 2.0 at diagnosis to 4.0 at relapse in the allo-cohort, in the conventionally treated patients from 0.9 to 1.3 (both P < .001).
  • Thus, higher frequencies of clonal evolution and increasing cytogenetic complexity were observed in the stem cell recipients probably related to the more unfavorable cytogenetic profiles already depicted at diagnosis.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation / methods. Leukemia, Myeloid, Acute / pathology. Leukemia, Myeloid, Acute / therapy

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  • [Copyright] Copyright © 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
  • (PMID = 20558312.001).
  • [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
  • [Publication-type] Journal Article
  • [Publication-country] United States
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2. Navarro WH, Agovi MA, Logan BR, Ballen K, Bolwell BJ, Frangoul H, Gupta V, Hahn T, Ho VT, Juckett M, Lazarus HM, Litzow MR, Liesveld JL, Moreb JS, Marks DI, McCarthy PL, Pasquini MC, Rizzo JD: Obesity does not preclude safe and effective myeloablative hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) in adults. Biol Blood Marrow Transplant; 2010 Oct;16(10):1442-50
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Obesity does not preclude safe and effective myeloablative hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) in adults.
  • We compared outcomes by body mass index (BMI) for adult patients with acute myelogenous leukemia (AML) who underwent autologous (auto, n = 373), related donor (RD, n = 2041), or unrelated donor (URD, n = 1801) allogeneic myeloablative hematopoietic cell transplantation (HCT) using bone marrow or peripheral blood stem cells reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 1995 to 2004.
  • Overweight and obese patients enjoyed a modest decrease in relapse incidence, although this did not translate into a survival benefit.

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  • [Copyright] Copyright © 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
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  • (PMID = 20412867.001).
  • [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 / NHLBI NIH HHS / HL / U01 HL069294; United States / NCI NIH HHS / CA / U24 CA076518; United States / NHLBI NIH HHS / HL / 5U01HL069294; United States / NCI NIH HHS / CA / U24-CA76518
  • [Publication-type] Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Myeloablative Agonists
  • [Other-IDs] NLM/ NIHMS210175; NLM/ PMC2933950
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3. Tallman MS, Pérez WS, Lazarus HM, Gale RP, Maziarz RT, Rowe JM, Marks DI, Cahn JY, Bashey A, Bishop MR, Christiansen N, Frankel SR, García JJ, Ilhan O, Laughlin MJ, Liesveld J, Linker C, Litzow MR, Luger S, McCarthy PL, Milone GA, Pavlovsky S, Phillips GL, Russell JA, Saez RA, Schiller G, Sierra J, Weiner RS, Zander AR, Zhang MJ, Keating A, Weisdorf DJ, Horowitz MM: Pretransplantation consolidation chemotherapy decreases leukemia relapse after autologous blood and bone marrow transplants for acute myelogenous leukemia in first remission. Biol Blood Marrow Transplant; 2006 Feb;12(2):204-16
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  • [Title] Pretransplantation consolidation chemotherapy decreases leukemia relapse after autologous blood and bone marrow transplants for acute myelogenous leukemia in first remission.
  • Controversy exists over whether pretransplantation consolidation chemotherapy affects the outcome of subsequent autotransplantation for acute myelogenous leukemia (AML).
  • The current study was undertaken to determine the association between previous consolidation and outcome of autotransplantation for AML in first remission.
  • Five-year relapse rates were 49% (95% confidence interval CI} = 39%-58%) with no consolidation, 35% (95% CI = 29%-42%) with standard-dose cytarabine, and 40% (95% CI = 33%-48%) with high-dose cytarabine (P = .07).
  • Five-year leukemia-free survival rates were 39% (95% CI = 30%-47%) with no consolidation, 53% (95% CI = 46%-60%) with standard-dose cytarabine, and 48% (95% CI = 40%-56%) with high-dose cytarabine (P = .03).
  • In multivariate analysis, risks of relapse and treatment failure were lower in the patients receiving consolidation, especially among those patients receiving blood cell grafts.
  • Based on our findings, we recommend that patients with AML in first remission receive consolidation before undergoing autotransplantation.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Bone Marrow Transplantation / mortality. Leukemia, Myeloid, Acute / mortality

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  • (PMID = 16443518.001).
  • [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
  • [Grant] United States / NCI NIH HHS / CA / U24-CA76518
  • [Publication-type] Comparative Study; 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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4. Ando T, Mitani N, Matsunaga K, Nakazora T, Gondo T, Yujiri T, Tanizawa Y: Gemtuzumab ozogamicin therapy for isolated extramedullary AML relapse after allogeneic hematopoietic stem-cell transplantation. Tohoku J Exp Med; 2010 Feb;220(2):121-6
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  • [Title] Gemtuzumab ozogamicin therapy for isolated extramedullary AML relapse after allogeneic hematopoietic stem-cell transplantation.
  • The treatment of isolated extramedullary relapse (IEMR) after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) poses a challenge for which no standard approach exists.
  • Gemtuzumab ozogamicin (GO) is a recombinant humanized monoclonal antibody, conjugated to calicheamicin, which targets the CD33 antigen that is expressed in acute myelogenous leukemia (AML) blasts.
  • The selectivity of GO for CD33-positive leukemic cells makes it an attractive agent for use in patients with multiple sites of IEMR after allo-HSCT, because GO does not suppress cells responsible for the putative graft-versus-leukemia (GVL) effect.
  • Herein, we describe a 54-year-old male patient who developed AML with multiple sites of extramedullary (EM) relapse after allo-HSCT, and who exhibited apparent donor-derived hematopoiesis in the bone marrow.
  • A biopsy specimen from a lumbar soft tissue mass confirmed EM relapse, and revealed that donor T lymphocytes were present in the relapse site and that leukemic cells expressed CD33.
  • GO can be an effective therapy for IEMR after allo-HSCT, especially when cytotoxic T lymphocytes react to leukemic cells at the site of EM relapse.
  • [MeSH-major] Aminoglycosides / therapeutic use. Antibodies, Monoclonal / therapeutic use. Hematopoietic Stem Cell Transplantation. Leukemia, Myeloid, Acute / therapy. Sarcoma, Myeloid / drug therapy
  • [MeSH-minor] Antibodies, Monoclonal, Humanized. Antineoplastic Agents / therapeutic use. Bone and Bones / radionuclide imaging. CD8-Positive T-Lymphocytes / pathology. Graft vs Leukemia Effect / immunology. Humans. Leukocytes / metabolism. Leukocytes / pathology. Lumbosacral Region / pathology. Lumbosacral Region / radionuclide imaging. Male. Middle Aged. Peroxidase / metabolism. Recurrence. Transplantation, Homologous

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  • (PMID = 20139663.001).
  • [ISSN] 1349-3329
  • [Journal-full-title] The Tohoku journal of experimental medicine
  • [ISO-abbreviation] Tohoku J. Exp. Med.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Aminoglycosides; 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antineoplastic Agents; 0 / gemtuzumab; EC 1.11.1.7 / Peroxidase
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5. Schlenk RF, Pasquini MC, Pérez WS, Zhang MJ, Krauter J, Antin JH, Bashey A, Bolwell BJ, Büchner T, Cahn JY, Cairo MS, Copelan EA, Cutler CS, Döhner H, Gale RP, Ilhan O, Lazarus HM, Liesveld JL, Litzow MR, Marks DI, Maziarz RT, McCarthy PL, Nimer SD, Sierra J, Tallman MS, Weisdorf DJ, Horowitz MM, Ganser A, CIBMTR Acute Leukemia Working Committee: HLA-identical sibling allogeneic transplants versus chemotherapy in acute myelogenous leukemia with t(8;21) in first complete remission: collaborative study between the German AML Intergroup and CIBMTR. Biol Blood Marrow Transplant; 2008 Feb;14(2):187-96
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  • [Title] HLA-identical sibling allogeneic transplants versus chemotherapy in acute myelogenous leukemia with t(8;21) in first complete remission: collaborative study between the German AML Intergroup and CIBMTR.
  • We studied the role of HLA-matched sibling hematopoietic cell transplantation (HCT) in treating t(8;21) acute myelogenous leukemia (AML) in first remission.
  • Outcomes of 118 patients receiving HCT and reported to the Center for International Blood and Marrow Transplant Research were compared with 132 similar patients receiving chemotherapy selected from 8 German AML Intergroup multicenter trials.
  • Transplants were associated with higher treatment-related mortality (TRM; relative risk [RR] 6.76, 95% confidence interval [CI] 2.95-15.45, P < .001), lower relapse (RR 0.47, 95% CI 0.25-0.85, P = .01), and similar relapse-free survival (P = .2).
  • In both cohorts, white blood cell count (WBC) at diagnosis >25 x 10(9)/L was associated with a higher relapse risk (RR = 2.09, P = .03), lower relapse-free (RR = 1.9, P = .008), and OS (RR = 1.91, P = .01).
  • In this cohort of patients with t(8;21) AML, HCT did not improve OS, because reduction of relapse was offset by high TRM.
  • These results suggest that patients with t(8;21) AML without poor prognostic factors have higher rates of survival after chemotherapy as a post remission therapy compared to HCT.

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  • (PMID = 18215779.001).
  • [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 / U24 CA076518-10; United States / NCI NIH HHS / CA / U24 CA076518; United States / NCI NIH HHS / CA / U24 CA076518-09; United States / NCI NIH HHS / CA / U24-CA76518; United States / NCI NIH HHS / CA / U24 CA076518-08; United States / NCI NIH HHS / CA / CA076518-08
  • [Publication-type] Comparative Study; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
  • [Publication-country] United States
  • [Other-IDs] NLM/ NIHMS39951; NLM/ PMC2531160
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6. King ME, Rowe JM: Recent developments in acute myelogenous leukemia therapy. Oncologist; 2007;12 Suppl 2:14-21
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  • [Title] Recent developments in acute myelogenous leukemia therapy.
  • Recent progress has been made in several areas in the treatment of acute myelogenous leukemia (AML): prognostic factors, allogeneic bone marrow transplantation, and new and targeted therapies.
  • The use of alternative donors is another advance, and recent data are promising, but survival is poor if transplantation is performed when disease is active, especially during refractory relapse or refractory disease.
  • Cord blood has also been established as a suitable source for hematopoietic transplantation in AML.
  • Therapy can even be tailored to several specific genetic subtypes of AML.
  • [MeSH-major] Leukemia, Myeloid / therapy
  • [MeSH-minor] Acute Disease. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Bone Marrow Transplantation. Humans

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  • (PMID = 18039635.001).
  • [ISSN] 1083-7159
  • [Journal-full-title] The oncologist
  • [ISO-abbreviation] Oncologist
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 41
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7. Ando T, Mitani N, Matsui K, Yamashita K, Nomiyama J, Tsuru M, Yujiri T, Tanizawa Y: Recurrent extramedullary relapse of acute myelogenous leukemia after allogeneic hematopoietic stem cell transplantation in a patient with the chromosomal abnormality t(8;21) and CD56-positivity. Int J Hematol; 2009 Oct;90(3):374-7
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  • [Title] Recurrent extramedullary relapse of acute myelogenous leukemia after allogeneic hematopoietic stem cell transplantation in a patient with the chromosomal abnormality t(8;21) and CD56-positivity.
  • Isolated extramedullary (EM) relapse of acute myelogenous leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rare.
  • We describe an AML patient showing the chromosomal abnormality t(8;21) and CD56 expression who experienced a unique EM relapse after allo-HSCT.
  • Approximately 10 months after allo-HSCT, he experienced relapse involving the femur and lumbar vertebrae and, subsequently, an EM relapse of the stomach.
  • Although we administered only local radiotherapy and not systemic chemotherapy, he showed no bone marrow relapse on long-term follow-up after achieving complete hematological remission.
  • These findings suggest that the graft-versus-leukemia effect may preferentially maintain marrow remission rather than prevent EM relapse.
  • In addition, our findings show that extended survival is possible after EM relapse following allo-HSCT in patients with marrow hematopoiesis of donor origin, and that augmentation of the graft-versus-leukemia effect may be useful.
  • [MeSH-major] Graft vs Leukemia Effect. Hematopoietic Stem Cell Transplantation. Leukemia, Myeloid, Acute. Stomach Neoplasms. Translocation, Genetic


8. Medeiros BC, Minden MD, Schuh AC, Schimmer AD, Yee K, Lipton JH, Messner HA, Gupta V, Chun K, Xu W, Das P, Kamel-Reid S, Brandwein JM: Characteristics and outcomes of acute myelogenous leukemia patients with very late relapse (&gt;5 years). Leuk Lymphoma; 2007 Jan;48(1):65-71
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  • [Title] Characteristics and outcomes of acute myelogenous leukemia patients with very late relapse (>5 years).
  • The clinical characteristics and outcome of 15 patients with acute myelogenous leukemia (AML) who experienced relapse at least 5 years after induction of complete remission (very late-relapse AML) are described.
  • There were eight males in this cohort and the median age at diagnosis was 48 years (range 13 - 77 years).
  • The 5-year relapse-free survival and overall survival rates of this cohort were 59% and 51%, respectively.
  • We conclude that very late-relapse AML is a rare event, and that reinduction in these patients is associated with very high CR rates and a potential cure fraction.
  • [MeSH-major] Leukemia, Myeloid, Acute / diagnosis


9. Gutierrez-Aguirre CH, Cantú-Rodríguez OG, Gonzalez-Llano O, Salazar-Riojas R, Martinez-González O, Jaime-Pérez JC, Morales-Toquero A, Tarín-Arzaga LC, Ruiz-Argüelles GJ, Gómez-Almaguer D: Non-myeloablative hematopoietic stem cell transplantation is of limited value in advanced or refractory acute myeloblastic leukemia. The Mexican experience. Hematology; 2007 Jun;12(3):193-7
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  • [Title] Non-myeloablative hematopoietic stem cell transplantation is of limited value in advanced or refractory acute myeloblastic leukemia. The Mexican experience.
  • Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective strategy for preventing relapse of acute myelogenous leukemia (AML).
  • We analyzed the outcome of 31 primary AML patients who received a reduced-intensity conditioning regimen for allogeneic HSCT in first or second remission.
  • Thirty-one AML patients, 20 in first complete remission (FCR), 8 in second complete remission (SCR) and 3 in a partial remission (SPR) were included.
  • Relapse for 20 patients in FCR was 35% compared to 91% for 11 in SCR/SPR (p < 0.05).
  • Conclusions. Reduced-intensity conditioning followed by allogeneic HSCT can induce stable remission in primary AML patients transplanted in FCR.
  • A high relapse rate was documented in patients with refractory or relapsed AML.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Hematopoietic Stem Cell Transplantation / methods. Leukemia, Myeloid, Acute / therapy

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  • (PMID = 17558694.001).
  • [ISSN] 1607-8454
  • [Journal-full-title] Hematology (Amsterdam, Netherlands)
  • [ISO-abbreviation] Hematology
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 83HN0GTJ6D / Cyclosporine; 8N3DW7272P / Cyclophosphamide; FA2DM6879K / Vidarabine; G1LN9045DK / Busulfan; P2K93U8740 / fludarabine
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10. Kobayashi R, Tawa A, Hanada R, Horibe K, Tsuchida M, Tsukimoto I, Japanese childhood AML cooperative study group: Extramedullary infiltration at diagnosis and prognosis in children with acute myelogenous leukemia. Pediatr Blood Cancer; 2007 Apr;48(4):393-8
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  • [Title] Extramedullary infiltration at diagnosis and prognosis in children with acute myelogenous leukemia.
  • BACKGROUND: Extramedullary infiltration (EMI) is an occasional clinical symptom in childhood acute myelogenous leukemia (AML), but there is considerable controversy regarding the prognostic significance of EMI in AML.
  • PROCEDURE: We evaluated the frequency and prognostic significance of EMI at diagnosis of AML in children.
  • RESULTS: Of 240 cases of de novo AML excluding children with Down syndrome and acute promyelocytic leukemia, 56 (23.3%) showed EMI at diagnosis.
  • A detailed analysis showed that patients with EMI with a WBC count at diagnosis of over 100 x 10(9)/L or infiltration into the central nervous system are likely to have a poor prognosis.
  • CONCLUSIONS: CNS leukemia and EMI together with a WBC count of >100 x 10(9)/L at diagnosis of AML are high risk factors for relapse, and alternative treatment approaches for patients with these characteristics should be explored.
  • [MeSH-major] Leukemia, Myeloid / pathology. Leukemic Infiltration / epidemiology. Sarcoma, Myeloid / epidemiology
  • [MeSH-minor] Acute Disease. Adolescent. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Bone and Bones / pathology. Central Nervous System / pathology. Child. Child, Preschool. Cytarabine / administration & dosage. Disease-Free Survival. Etoposide / administration & dosage. Female. Follow-Up Studies. Gingiva / pathology. Humans. Hydrocortisone / administration & dosage. Idarubicin / administration & dosage. Infant. Infant, Newborn. Japan / epidemiology. Kaplan-Meier Estimate. Male. Methotrexate / administration & dosage. Orbit / pathology. Prognosis. Remission Induction. Skin / pathology. Testis / pathology

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  • (PMID = 16550530.001).
  • [ISSN] 1545-5009
  • [Journal-full-title] Pediatric blood & cancer
  • [ISO-abbreviation] Pediatr Blood Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 6PLQ3CP4P3 / Etoposide; WI4X0X7BPJ / Hydrocortisone; YL5FZ2Y5U1 / Methotrexate; ZRP63D75JW / Idarubicin
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11. Russell JA, Irish W, Balogh A, Chaudhry MA, Savoie ML, Turner AR, Larratt L, Storek J, Bahlis NJ, Brown CB, Quinlan D, Geddes M, Zacarias N, Daly A, Duggan P, Stewart DA: The addition of 400 cGY total body irradiation to a regimen incorporating once-daily intravenous busulfan, fludarabine, and antithymocyte globulin reduces relapse without affecting nonrelapse mortality in acute myelogenous leukemia. Biol Blood Marrow Transplant; 2010 Apr;16(4):509-14
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] The addition of 400 cGY total body irradiation to a regimen incorporating once-daily intravenous busulfan, fludarabine, and antithymocyte globulin reduces relapse without affecting nonrelapse mortality in acute myelogenous leukemia.
  • A combination of fludarabine (Flu) and daily i.v. busulfan (Bu) is well tolerated and effective in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML).
  • The addition of rabbit antithymocyte globulin (ATG) may reduce morbidity and mortality from graft-versus-host disease (GVHD), but lead to increased relapse.
  • Although nonrelapse mortality (NRM) at 3 years did not differ between the groups, the inclusion of TBI significantly reduced relapse (hazard ratio [HR] = 0.29; 95% confidence interval [CI] = 0.15-0.54; P = .0001).
  • This study confirms the importance of regimen intensity in allogeneic HSCT for AML.
  • Bu, Flu, 400 cGy TBI, and ATG provides a well-tolerated regimen with antileukemic activity in AML comparable to that of other, conventional myeloablative (MA) regimens.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Hematopoietic Stem Cell Transplantation / methods. Leukemia, Myeloid, Acute / therapy

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  • [Copyright] Copyright (c) 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
  • (PMID = 19948235.001).
  • [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
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antilymphocyte Serum; FA2DM6879K / Vidarabine; G1LN9045DK / Busulfan; P2K93U8740 / fludarabine
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12. Kalaycio M, Advani A, Pohlman B, Sekeres M, Tripp B, Rybicki L, Sobecks R: Timed sequential induction chemotherapy and risk-adapted postremission therapy for acute myelogenous leukemia. Am J Hematol; 2008 Nov;83(11):831-4
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  • [Title] Timed sequential induction chemotherapy and risk-adapted postremission therapy for acute myelogenous leukemia.
  • Cytogenetic analysis at the time of diagnosis predicts outcome in patients with acute myelogenous leukemia (AML).
  • For those patients with favorable risk cytogenetics, stem cell transplant can be delayed until the time of relapse.
  • We treated patients with de novo AML and age less than 60 years first with etoposide, mitoxantrone, cytarabine, and G-CSF (EMA-G) to induce remission.
  • Of the 33 patients in remission, 5 year relapse-free survival (RFS) and overall survival (OS) was 46 and 38%, respectively.
  • Our intensive and risk-adapted, stem cell transplant approach to the treatment of patients with AML requires a better definition of risk and does not appear to substantially improve results compared with more standard approaches.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Granulocyte Colony-Stimulating Factor / administration & dosage. Hematopoietic Stem Cell Transplantation. Leukemia, Myeloid, Acute / drug therapy

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  • [Copyright] Copyright 2008 Wiley-Liss, Inc.
  • [CommentIn] Am J Hematol. 2008 Nov;83(11):829-30 [18828158.001]
  • (PMID = 18756545.001).
  • [ISSN] 1096-8652
  • [Journal-full-title] American journal of hematology
  • [ISO-abbreviation] Am. J. Hematol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 6PLQ3CP4P3 / Etoposide; BZ114NVM5P / Mitoxantrone
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13. Lipton J, Joffe S, Ullrich NJ: CNS relapse of acute myelogenous leukemia masquerading as pseudotumor cerebri. Pediatr Neurol; 2008 Nov;39(5):355-7
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] CNS relapse of acute myelogenous leukemia masquerading as pseudotumor cerebri.
  • An 18-year-old man in remission from acute myelogenous leukemia 3 years after a bone marrow transplant presented with signs of pseudotumor cerebri, including headache, visual changes, and papilledema.
  • He was diagnosed with an isolated central nervous system relapse of acute myeloid leukemia.
  • Although the precise etiology remains elusive, this case demonstrates that pseudotumor cerebri must remain within the differential diagnosis after other complications are excluded, particularly in persons with underlying hematologic malignancies.
  • [MeSH-major] Leukemia, Myeloid, Acute / complications. Leukemia, Myeloid, Acute / diagnosis. Pseudotumor Cerebri / diagnosis. Pseudotumor Cerebri / etiology
  • [MeSH-minor] Adolescent. Biopsy. Diagnosis, Differential. Humans. Male. Recurrence


14. Spoo AC, Lübbert M, Wierda WG, Burger JA: CXCR4 is a prognostic marker in acute myelogenous leukemia. Blood; 2007 Jan 15;109(2):786-91
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  • [Title] CXCR4 is a prognostic marker in acute myelogenous leukemia.
  • CXCR4 chemokine receptors retain hematopoietic progenitors and leukemia cells within the marrow microenvironment.
  • We prospectively evaluated the prognostic implication of CXCR4 in 90 consecutive patients with acute myelogenous leukemia (AML) by flow cytometry.
  • We found that low CXCR4 expression on AML cells correlated with a better prognosis, resulting in a longer relapse-free and overall survival of 24.3+/-2.9 months for low CXCR4-expressing patients, compared with 17.4+/-3.4 months for intermediate and 12.8+/-2 months (mean+/-SEM) for patients with high expression.
  • We conclude that CXCR4 expression in AML is an independent prognostic predictor for disease relapse and survival that can rapidly and easily be determined at disease presentation.
  • These findings warrant further investigation into the role of CXCR4 in AML and suggest that CXCR4 should be incorporated into the risk assessment of AML patients.
  • [MeSH-major] Biomarkers, Tumor / metabolism. Leukemia, Myeloid, Acute / diagnosis. Leukemia, Myeloid, Acute / metabolism. Receptors, CXCR4 / metabolism

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  • (PMID = 16888090.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Receptors, CXCR4
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15. Shen YM, Chao HY, Zhang R, Li WY, Feng YF, Zhu ZL, Xue YQ: [Detection of JAK2V617F mutation and its clinical significance in 80 patients with M2 acute myelogenous leukemia]. Zhonghua Zhong Liu Za Zhi; 2009 May;31(5):366-70
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  • [Title] [Detection of JAK2V617F mutation and its clinical significance in 80 patients with M2 acute myelogenous leukemia].
  • OBJECTIVE: To explore the prevalence and prognostic significance of JAK2V617F gene mutation in acute myelogenous leukemia M2 (AML-M2) patients.
  • RESULTS: Of 80 de novo AML-M2 patients, 6 at the time of first diagnosis and 1 at relapse were found to have JAK2V617F gene mutation (8.8%, 7/80).
  • Morphologically, the whole blood and bone marrow of the 7 AML-M2 patients with JAK2V617F gene mutation presented a picture of acute leukemia instead of myeloproliferative disorders.
  • Immunophenotypically, bone marrow samples showed myelogenous linage expression.
  • Complete remission was obtained in 4 of 5 AML-M2 patients with JAK2V617F mutation who received treatment, while one patient had no response to the treatment.
  • CONCLUSION: JAK2V617F gene mutation, as a type-1 mutation, might not be an initial event in the pathogenesis of acute myelogenous leukemia, and its presentation does not mean a poor prognosis in de novo AML patients.
  • [MeSH-major] Janus Kinase 2 / genetics. Leukemia, Myeloid, Acute / genetics. Mutation

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  • (PMID = 19799086.001).
  • [ISSN] 0253-3766
  • [Journal-full-title] Zhonghua zhong liu za zhi [Chinese journal of oncology]
  • [ISO-abbreviation] Zhonghua Zhong Liu Za Zhi
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 0 / DNA, Neoplasm; EC 2.7.10.2 / JAK2 protein, human; EC 2.7.10.2 / Janus Kinase 2
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16. Guzman ML, Rossi RM, Karnischky L, Li X, Peterson DR, Howard DS, Jordan CT: The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells. Blood; 2005 Jun 1;105(11):4163-9
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  • [Title] The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells.
  • Recent studies have described malignant stem cells as central to the initiation, growth, and potential relapse of acute and chronic myelogenous leukemia (AML and CML).
  • Because of their important role in pathogenesis, rare and biologically distinct leukemia stem cells (LSCs) represent a critical target for therapeutic intervention.
  • The present studies demonstrate that parthenolide (PTL), a naturally occurring small molecule, induces robust apoptosis in primary human AML cells and blast crisis CML (bcCML) cells while sparing normal hematopoietic cells.
  • Furthermore, analysis of progenitor cells using in vitro colony assays, as well as stem cells using the nonobese diabetic/severe combined immunodeficient (NOD/SCID) xenograft model, show that PTL also preferentially targets AML progenitor and stem cell populations.
  • Notably, in comparison to the standard chemotherapy drug cytosine arabinoside (Ara-C), PTL is much more specific to leukemia cells.

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  • (PMID = 15687234.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R01-CA90446
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Lactones; 0 / NF-kappa B; 0 / Reactive Oxygen Species; 0 / Sesquiterpenes; 0 / Tumor Suppressor Protein p53; 2RDB26I5ZB / parthenolide
  • [Other-IDs] NLM/ PMC1895029
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17. Kikushige Y, Takase K, Sata K, Aoki K, Numata A, Miyamoto T, Fukuda T, Gondo H, Harada M, Nagafuji K: Repeated relapses of acute myelogenous leukemia in the isolated extramedullary sites following allogeneic bone marrow transplantations. Intern Med; 2007;46(13):1011-4
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  • [Title] Repeated relapses of acute myelogenous leukemia in the isolated extramedullary sites following allogeneic bone marrow transplantations.
  • Isolated extramedullary (EM) relapses of acute myelogenous leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) have been reported to be rare, and are usually followed by bone marrow relapses.
  • We report a 49-year-old man with AML with the unfavorable chromosome abnormality 7q-, who was treated by allo-HSCT.
  • Fifteen months after allo-HSCT, the patient initially developed a relapse only in his inguinal lymph nodes, and then bone marrow relapse became evident one month after the EM relapse.
  • Subsequently, the patient received chemotherapy and a second allo-HSCT from another donor, but he suffered another relapse in different EM sites including the skin and central nervous system with a persistently normal marrow.
  • This case is characterized by repeated relapses in isolated EM sites after allo-HSCT and suggests that the anti-leukemic effects of chemotherapy and/or graft-versus-leukemia effects in the EM sites might not be so uniformly effective as that in the marrow.
  • Accordingly, we should be aware that AML relapses can occur repeatedly only in isolated EM sites post allo-HSCT, resulting in treatment failure and a poor prognosis.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation / methods. Leukemia, Myeloid, Acute / pathology. Leukemia, Myeloid, Acute / therapy. Leukemic Infiltration / pathology. Lymph Nodes / pathology

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  • (PMID = 17603242.001).
  • [ISSN] 1349-7235
  • [Journal-full-title] Internal medicine (Tokyo, Japan)
  • [ISO-abbreviation] Intern. Med.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Japan
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18. Ooi J, Takahashi S, Tomonari A, Tsukada N, Konuma T, Kato S, Kasahara S, Sato A, Monma F, Nagamura F, Iseki T, Tojo A, Asano S: Unrelated cord blood transplantation after myeloablative conditioning in adults with acute myelogenous leukemia. Biol Blood Marrow Transplant; 2008 Dec;14(12):1341-7
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  • [Title] Unrelated cord blood transplantation after myeloablative conditioning in adults with acute myelogenous leukemia.
  • We analyzed the disease-specific outcomes of adult acute myelogenous leukemia (AML) patients treated with unrelated cord blood transplantation (CBT) after myeloablative conditioning.
  • Between August 1998 and February 2008, 77 adult patients with AML were treated with unrelated CBT.
  • The cumulative incidence of grade III to IV acute graft-versus-host disease (aGVHD) and extensive-type chronic GVHD (cGVHD) was 25.1% and 28.6%, respectively.
  • The 5-year cumulative incidence of treatment related-mortality (TRM) and relapse was 9.7%, 25.8%, respectively.
  • These results suggest that unrelated CBT after myeloablative conditioning could be safely and effectively used for adult patients with AML.
  • [MeSH-major] Cord Blood Stem Cell Transplantation. HLA Antigens. Leukemia, Myeloid, Acute / therapy. Transplantation Conditioning
  • [MeSH-minor] Acute Disease. Adolescent. Adult. Aged. Antigens, CD34. Disease-Free Survival. Female. Graft vs Host Disease / mortality. Graft vs Host Disease / prevention & control. Humans. Incidence. Male. Middle Aged. Neutrophils. Recovery of Function. Survival Rate. Transplantation, Homologous

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  • (PMID = 19041055.001).
  • [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
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, CD34; 0 / HLA Antigens
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19. Petersen WC, Schlis KD, Braverman RS, Carlson I, Liang X, Wang M: Pseudohypopyon: Extramedullary relapse of acute myelogenous leukemia with poor prognosis. Pediatr Blood Cancer; 2009 Jul;52(7):885-7
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  • [Title] Pseudohypopyon: Extramedullary relapse of acute myelogenous leukemia with poor prognosis.
  • She was diagnosed with acute myelogenous leukemia.
  • Towards the end of her second course of induction she developed pseudohypopyon in each eye on consecutive days, heralding a central nervous system relapse.
  • [MeSH-major] Anterior Chamber / pathology. Eye Diseases / diagnosis. Leukemia, Myelomonocytic, Acute / diagnosis. Neoplasm Recurrence, Local / diagnosis
  • [MeSH-minor] Antimetabolites, Antineoplastic / therapeutic use. Cytarabine / therapeutic use. Female. Humans. Infant. Injections, Spinal. Prognosis. Suppuration / diagnosis

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  • [Copyright] (c) 2008 Wiley-Liss, Inc.
  • (PMID = 19090546.001).
  • [ISSN] 1545-5017
  • [Journal-full-title] Pediatric blood & cancer
  • [ISO-abbreviation] Pediatr Blood Cancer
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 04079A1RDZ / Cytarabine
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20. Hartwig M, Weigel S, Bernig T, Bader P, Dölken R, Beck J: Maintenance immunotherapy by repetitive low-dose donor lymphocytes infusions in a child with relapse state aml after allogeneic stem cell transplantation. Pediatr Hematol Oncol; 2007 Mar;24(2):137-40
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  • [Title] Maintenance immunotherapy by repetitive low-dose donor lymphocytes infusions in a child with relapse state aml after allogeneic stem cell transplantation.
  • The treatment of a child with a relapsed state acute leukemia after allogeneic stem cell transplantation (allo-SCT) is a challenge.
  • The authors report about a child with an acute myelogenous leukemia (AML), which relapsed after allo-SCT despite immunological intervention.
  • Because of an immense risk for a further relapse, an immunological maintenance therapy was also performed, consisting of repetitive infusions of low doses of donor lymphocytes combined with low-dose chemotherapy.
  • [MeSH-major] Graft vs Host Disease / therapy. Leukemia, Myeloid, Acute / therapy. Lymphocyte Transfusion. Stem Cell Transplantation

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  • (PMID = 17454780.001).
  • [ISSN] 1521-0669
  • [Journal-full-title] Pediatric hematology and oncology
  • [ISO-abbreviation] Pediatr Hematol Oncol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
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26. Huisman C, Meijer E, Petersen EJ, Lokhorst HM, Verdonck LF: Hematopoietic stem cell transplantation after reduced intensity conditioning in acute myelogenous leukemia patients older than 40 years. Biol Blood Marrow Transplant; 2008 Feb;14(2):181-6
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  • [Title] Hematopoietic stem cell transplantation after reduced intensity conditioning in acute myelogenous leukemia patients older than 40 years.
  • We analyzed the outcome of RIC HSCT in acute myelogenous leukemia (AML) patients over the age of 40 years.
  • Forty-three AML or high-risk myelodysplastic syndrome (MDS) patients were treated with a fludarabine and low-dose total-body irradiation (TBI)-based pretransplantation regimen.
  • All but 2 AML patients were in complete remission (CR) at the time of transplantation.
  • Two patients with active disease at the time of HSCT experienced ongoing relapse.
  • Sixty percent of patients developed acute graft-versus-host disease (aGVHD), which was grade II in 40% and grade III in 12%.
  • After a median follow-up of 571 days, 16 patients (37%) experienced relapse.
  • In conclusion, fludarabine plus low-dose TBI-based RIC HSCT is effective in AML patients over the age of 40 years without active disease at the time of transplant and is associated with low TRM.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation / methods. Leukemia, Myeloid, Acute / therapy. Transplantation Conditioning / methods

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  • (PMID = 18215778.001).
  • [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
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine
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27. Moore J, Nivison-Smith I, Goh K, Ma D, Bradstock K, Szer J, Durrant S, Schwarer A, Bardy P, Herrmann R, Dodds A: Equivalent survival for sibling and unrelated donor allogeneic stem cell transplantation for acute myelogenous leukemia. Biol Blood Marrow Transplant; 2007 May;13(5):601-7
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  • [Title] Equivalent survival for sibling and unrelated donor allogeneic stem cell transplantation for acute myelogenous leukemia.
  • Recent studies have shown comparable survival outcomes for unrelated donor (URD) stem cell transplantation in chronic myelogenous leukemia compared to sibling donors.
  • We compared outcomes for 105 patients aged 16 to 59 years undergoing URD transplants for acute myelogenous leukemia (AML) who were reported to the Australasian Bone Marrow Transplant Recipient Registry between 1992 and 2002, and a strictly selected matching set of 105 HLA-matched sibling donor (MSD) transplants.
  • There was no significant difference between URD and MSD controls in the distributions of time from diagnosis to transplant, donor-recipient sex match, prior therapies, donor age, or performance status.
  • There was no difference in the cumulative incidence of acute graft-versus-host disease grade II or above at 100 days.
  • Relapse occurred in 28% of good risk URD subjects and 16% of siblings (P = .3), and in poor risk subjects 39% and 29%, respectively (P = .2).
  • Based on this data, URD allografts should be considered in AML patients without a matched sibling donor.
  • This study provides a rationale for a larger prospective study of risk factors in allogeneic transplantation for AML and a guide on the subset of patients who may most benefit from an unrelated donor allograft in AML.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation / adverse effects. Leukemia, Myeloid, Acute / therapy

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  • (PMID = 17448920.001).
  • [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] Comparative Study; Journal Article
  • [Publication-country] United States
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28. 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


29. Lashkari A, Lowe T, Collisson E, Paquette R, Emmanouilides C, Territo M, Schiller G: Long-term outcome of autologous transplantation of peripheral blood progenitor cells as postremission management of patients &gt; or =60 years with acute myelogenous leukemia. Biol Blood Marrow Transplant; 2006 Apr;12(4):466-71
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  • [Title] Long-term outcome of autologous transplantation of peripheral blood progenitor cells as postremission management of patients > or =60 years with acute myelogenous leukemia.
  • The optimal postremission treatment for elderly patients with acute myelogenous leukemia (AML) is presently unknown, but recent studies report the feasibility of autologous stem cell transplantation in this population.
  • To better understand the long-term outcome of autologous transplantation in AML patients > or =60 years of age, we evaluated high-dose chemoradiotherapy preparative conditioning followed by transplantation of peripheral blood progenitor cells procured after a single cycle of cytarabine-based consolidation chemotherapy as postremission therapy in 27 patients aged 60 to 71 years (median age, 65 years) with newly diagnosed AML in first complete remission (CR).
  • Seven patients are alive in continuous CR, 19 died from relapse, and 1 died as a result of treatment-related infection.
  • Leukemia-free survival and overall survival are 10.3 and 13.4 months, respectively.
  • Actuarial leukemia-free and overall survival at 3 years are 25% +/- 9% and 28% +/- 9%, respectively.
  • Our results demonstrate that autologous transplantation of peripheral blood progenitor cells is well tolerated and feasible for patients > or =60 years of age with AML in first CR.
  • [MeSH-major] Leukemia, Myeloid, Acute / mortality. Peripheral Blood Stem Cell Transplantation. Transplantation Conditioning

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  • (PMID = 16545730.001).
  • [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; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Immunosuppressive Agents; 04079A1RDZ / Cytarabine
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30. Liu H, Qian WB, Mai WY, Meng HT, Tong HY, Tong Y, Mao LP, Huang J, Wang L, Jiang DZ, Jin J: [HAA regimen as induction chemotherapy for newly diagnosed acute myelogenous leukemia]. Zhonghua Xue Ye Xue Za Zhi; 2008 Jan;29(1):9-12
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  • [Title] [HAA regimen as induction chemotherapy for newly diagnosed acute myelogenous leukemia].
  • OBJECTIVE: To analyse the outcome of newly diagnosed adult acute myeloid leukemia (AML) patients treated with HAA (homoharringtonine, cytarabine and aclarubicin) regimen and explore the efficacy and safety of this regimen.
  • Kaplan-Meier method was used to estimate relapse free survival (RFS) rate and the differences were compared with 2-sided log-rank test.
  • For the AML-M5 and AML-M /M2 patients the CR rate was 74% and 87% and 3 year RFS of CR patients was 75% and 37%, respectively.
  • CONCLUSION: HAA regimen is a safe, efficacious, and well-tolerable induction therapy for newly diagnosed AML.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid, Acute / drug therapy

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  • (PMID = 18512308.001).
  • [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] English Abstract; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Harringtonines; 04079A1RDZ / Cytarabine; 6FG8041S5B / homoharringtonine; 74KXF8I502 / Aclarubicin
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31. Huh HJ, Huh JW, Yoo ES, Seong CM, Lee M, Hong KS, Chung WS: hTERT mRNA levels by real-time RT-PCR in acute myelogenous leukemia. Am J Hematol; 2005 Aug;79(4):267-73
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  • [Title] hTERT mRNA levels by real-time RT-PCR in acute myelogenous leukemia.
  • The purpose of this study was to investigate whether levels of hTERT mRNA, as determined by real-time RT-PCR, are associated with prognosis and clinical course in AML patients.
  • Fifty-four bone marrow specimens from 21 patients diagnosed with de-novo AML were included.
  • The expression rates of hTERT mRNA were significantly higher at diagnosis (73%) and during relapse (80%) than during remission (27%) (P<0.05).
  • The median RR for diagnosis or relapse was significantly higher than that for patients in remission (P<0.05).
  • Among seven patients with high hTERT mRNA levels (RR>9.51), 4 failed to achieve complete remission (CR), whereas 4 of 5 patients without hTERT mRNA expression at diagnosis or during relapse achieved CR (P>0.05).
  • Patients showing a trend of increasing hTERT mRNA levels failed to reach a second CR after relapse, while those with a trend toward decreasing hTERT mRNA did achieve CR.
  • Serial and quantitative analysis of hTERT mRNA may be a useful marker for prediction of prognosis and monitoring in AML patients.
  • [MeSH-major] Biomarkers, Tumor / analysis. DNA-Binding Proteins / analysis. Leukemia, Myeloid, Acute / diagnosis. RNA, Messenger / analysis. Telomerase / analysis

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  • [Copyright] Copyright (c) 2005 Wiley-Liss, Inc.
  • (PMID = 16044449.001).
  • [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 / Biomarkers, Tumor; 0 / DNA-Binding Proteins; 0 / RNA, Messenger; EC 2.7.7.49 / Telomerase
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32. van Besien K, Kunavakkam R, Rondon G, De Lima M, Artz A, Oran B, Giralt S: Fludarabine-melphalan conditioning for AML and MDS: alemtuzumab reduces acute and chronic GVHD without affecting long-term outcomes. Biol Blood Marrow Transplant; 2009 May;15(5):610-7
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  • [Title] Fludarabine-melphalan conditioning for AML and MDS: alemtuzumab reduces acute and chronic GVHD without affecting long-term outcomes.
  • The purpose of this study was to determine the effect of alemtuzumab on treatment-related mortality (TRM), relapse, overall survival (OS), and disease-free survival (DSF) in patients with acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS) undergoing reduced intensity conditioning (RIC).
  • There were no significant differences in TRM, relapse, survival, and DFS between the 2 groups.
  • The incidence of acute graft-versus-host disease (aGVHD) grade II-IV (relative risk [RR] 5.5, P < .01) and chronic GVHD (cGVHD) (RR 6.6, P < .01) were significantly lower in patients receiving alemtuzumab.
  • The addition of alemtuzumab to an RIC regimen dramatically reduces the incidence of aGVHD and cGVHD in patients with AML and MDS undergoing allogeneic transplantation.
  • TRM, relapse risk, OS and DFS are not affected.

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  • (PMID = 19361753.001).
  • [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 / K24 CA116471; United States / NCI NIH HHS / CA / P01 CA055164; United States / NCI NIH HHS / CA / R21 CA101337; United States / NCI NIH HHS / CA / 1-R21 CA 101337-01
  • [Publication-type] Controlled Clinical Trial; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antibodies, Neoplasm; 106XV160TZ / Vidarabine Phosphate; 1X9VK9O1SC / fludarabine phosphate; 3A189DH42V / alemtuzumab; Q41OR9510P / Melphalan
  • [Other-IDs] NLM/ NIHMS589065; NLM/ PMC4348112
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33. Alyea EP, Kim HT, Ho V, Cutler C, DeAngelo DJ, Stone R, Ritz J, Antin JH, Soiffer RJ: Impact of conditioning regimen intensity on outcome of allogeneic hematopoietic cell transplantation for advanced acute myelogenous leukemia and myelodysplastic syndrome. Biol Blood Marrow Transplant; 2006 Oct;12(10):1047-55
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  • [Title] Impact of conditioning regimen intensity on outcome of allogeneic hematopoietic cell transplantation for advanced acute myelogenous leukemia and myelodysplastic syndrome.
  • We reviewed 136 patients with advanced acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) undergoing allogeneic transplantation to assess the impact of conditioning regimen intensity on outcome.
  • The cumulative risk of relapse was higher for patients after NST (61% vs 38%; P = .02).
  • Despite the high-risk features of patients with advanced AML or MDS undergoing NST, OS and PFS in these patients was similar to those in patients receiving myeloablative transplantation.
  • These results suggest that NST is a reasonable alternative for patients with advanced AML and MDS at high risk for complications after myeloablative transplantation.
  • [MeSH-major] Bone Marrow Transplantation. Busulfan / administration & dosage. Cyclophosphamide / administration & dosage. Leukemia, Myeloid / surgery. Myelodysplastic Syndromes / surgery. Peripheral Blood Stem Cell Transplantation. Transplantation Conditioning. Vidarabine / analogs & derivatives. Whole-Body Irradiation
  • [MeSH-minor] Acute Disease. Adult. Aged. Female. Graft Survival. Graft vs Host Disease / epidemiology. Graft vs Host Disease / etiology. Humans. Incidence. Kaplan-Meier Estimate. Male. Middle Aged. Recurrence. Reoperation. Retrospective Studies. Tissue Donors. Transplantation, Homologous / mortality. Treatment Outcome


34. Hsu KC, Keever-Taylor CA, Wilton A, Pinto C, Heller G, Arkun K, O'Reilly RJ, Horowitz MM, Dupont B: Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes. Blood; 2005 Jun 15;105(12):4878-84
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  • [Title] Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes.
  • In 178 patients receiving T-cell-depleted HLA-identical sibling transplants for acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndrome (MDS), analysis of donor KIR genotype with HLA genotype demonstrated that 62.9% of the patients lacked an HLA ligand for donor-inhibitory KIR.
  • Lack of HLA ligand for donor-inhibitory KIR (missing KIR ligand) had no effect on disease-free survival (DFS), overall survival (OS), or relapse in patients receiving transplants for CML and ALL.
  • In patients with AML and MDS, however, there was a significant missing KIR ligand effect on DFS (P = .014; hazard ratio [HR], 0.53; 95% confidence interval [95% CI], 0.28-0.88) and OS (P = .03; HR, 0.53; 95% CI, 0.3-0.93).
  • Incidence of relapse was also lower in patients with AML and MDS who lacked the HLA ligand for donor-inhibitory KIR (P = .04; HR, 0.41; 95% CI, 0.18-0.97).
  • AML and MDS patients lacking 2 HLA ligands for donor-inhibitory KIR had the highest DFS (P = .002) and OS (P = .003).
  • These data indicate that the absence of class I ligand in the recipient for donor-inhibitory KIR can be a prognostic factor for transplantation outcome in HLA-identical sibling transplantation and that the lack of HLA-C or -B ligands for donor-inhibitory KIR can contribute to improved outcomes for patients with AML and MDS.

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  • (PMID = 15731175.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / NIAID NIH HHS / AI / AI49213; United States / NCI NIH HHS / CA / CA08748; United States / NCI NIH HHS / CA / CA23766; United States / NHLBI NIH HHS / HL / HL070053
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Epitopes; 0 / HLA Antigens; 0 / HLA-B Antigens; 0 / HLA-C Antigens; 0 / Ligands; 0 / Oligonucleotide Probes; 0 / Receptors, Immunologic; 0 / Receptors, KIR
  • [Other-IDs] NLM/ PMC1894998
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35. Cooley S, Weisdorf DJ, Guethlein LA, Klein JP, Wang T, Le CT, Marsh SG, Geraghty D, Spellman S, Haagenson MD, Ladner M, Trachtenberg E, Parham P, Miller JS: Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia. Blood; 2010 Oct 7;116(14):2411-9
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  • [Title] Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia.
  • We KIR genotyped donors from 1409 unrelated transplants for acute myelogenous leukemia (AML; n = 1086) and acute lymphoblastic leukemia (ALL; n = 323).
  • Donor KIR genotype influenced transplantation outcome for AML but not ALL.
  • Compared with A haplotype motifs, centromeric and telomeric B motifs both contributed to relapse protection and improved survival, but Cen-B homozygosity had the strongest independent effect.
  • With Cen-B/B homozygous donors the cumulative incidence of relapse was 15.4% compared with 36.5% for Cen-A/A donors (relative risk of relapse 0.34; 95% confidence interval 0.2-0.57; P < .001).
  • Overall, significantly reduced relapse was achieved with donors having 2 or more B gene-content motifs (relative risk 0.64; 95% confidence interval 0.48-0.86; P = .003) for both HLA-matched and mismatched transplants.
  • Adopting this practice could result in superior disease-free survival for patients with AML.

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  • (PMID = 20581313.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / NHLBI NIH HHS / HL / 5U01HL069294; United States / NCI NIH HHS / CA / P01 CA065493; United States / NCI NIH HHS / CA / U24 CA076518; United States / PHS HHS / / HHSH234200637015C; United States / NCI NIH HHS / CA / U24-CA76518; United States / NHLBI NIH HHS / HL / U01 HL069294; United States / PHS HHS / / P01 111412
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Receptors, KIR
  • [Other-IDs] NLM/ PMC2953880
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36. Pidala J, Kim J, Anasetti C, Kharfan-Dabaja MA, Nishihori T, Field T, Perkins J, Perez L, Fernandez HF: Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia. J Hematol Oncol; 2010;3:36
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  • [Title] Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia.
  • Optimal conditioning therapy for hematopoietic cell transplantation (HCT) in acute myelogenous leukemia (AML) remains undefined.
  • We retrospectively compared outcomes of a consecutive series of 51 AML patients treated with oral busulfan (1 mg/kg every 6 hours for 4 days) and cyclophosphamide (60 mg/kg IV × 2 days) - (Bu/Cy) with 100 consecutive AML patients treated with pharmacokinetic targeted IV busulfan (AUC < 6000 μM/L*min per day × 4 days) and fludarabine (40 mg/m2 × 4 days) - (t-IV Bu/Flu).
  • However, multivariable analysis did not demonstrate significant differences in overall survival (p = 0.78) or non-relapse mortality (p = 0.6) according to conditioning regimen delivered.
  • [MeSH-major] Busulfan / pharmacokinetics. Hematopoietic Stem Cell Transplantation. Leukemia, Myeloid, Acute / therapy. Transplantation Conditioning

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  • (PMID = 20925957.001).
  • [ISSN] 1756-8722
  • [Journal-full-title] Journal of hematology & oncology
  • [ISO-abbreviation] J Hematol Oncol
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 8N3DW7272P / Cyclophosphamide; FA2DM6879K / Vidarabine; G1LN9045DK / Busulfan; P2K93U8740 / fludarabine
  • [Other-IDs] NLM/ PMC2958877
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37. Oshima K, Kanda Y, Yamashita T, Takahashi S, Mori T, Nakaseko C, Fujimaki K, Yokota A, Fujisawa S, Matsushima T, Fujita H, Sakura T, Okamoto S, Maruta A, Sakamaki H, Kanto Study Group for Cell Therapy: Central nervous system relapse of leukemia after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant; 2008 Oct;14(10):1100-7
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  • [Title] Central nervous system relapse of leukemia after allogeneic hematopoietic stem cell transplantation.
  • Little information is available regarding central nervous system (CNS) relapse of adult leukemia after allogeneic hematopoietic stem cell transplantation (HSCT).
  • Therefore, we reviewed the data of 1226 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myelogenous leukemia (CML) who received first allogeneic HSCT between 1994 and 2004, using the database of the Kanto Study Group for Cell Therapy (KSGCT), and analyzed the incidence, risk factors, and outcome of patients with CNS relapse.
  • Twenty-nine patients developed CNS relapse at a median of 296 (9-1677) days after HSCT with a cumulative incidence of 2.3%.
  • Independent significant factors associated with CNS relapse included ALL as the underlying diagnosis (relative risk [RR] = 9.55, 95% confidence interval [CI] = 1.26-72.2, P = .029), nonremission at HSCT (RR = 2.30, 95% CI = 1.03-5.15, P = .042), the history of CNS invasion before HSCT (RR = 5.62, 95% CI = 2.62-12.0, P = 9.2 x 10(-6)), and the prophylactic intrathecal chemotherapy after HSCT (RR = 2.57, 95% CI = 1.21-5.46, P = .014).
  • The 3-year overall survival (OS) after CNS relapse was 18%.
  • In 7 of 29 patients with CNS relapse, leukemia was observed only in CNS.
  • Three of 7 patients were alive without systemic relapse, resulting in 3-year survival after CNS relapse of 46%.
  • Although the outcome of patients with CNS relapse was generally poor, long-term disease-free survival could be achieved in some patients.
  • [MeSH-major] Central Nervous System Neoplasms / etiology. Hematopoietic Stem Cell Transplantation. Leukemia / pathology. Leukemia / therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Disease-Free Survival. Female. Humans. Incidence. Leukemia, Myelogenous, Chronic, BCR-ABL Positive. Leukemia, Myeloid, Acute. Leukemic Infiltration. Male. Middle Aged. Precursor Cell Lymphoblastic Leukemia-Lymphoma. Recurrence. Retrospective Studies. Risk Factors. Survival Rate. Transplantation, Homologous. Treatment Outcome

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  • (PMID = 18804039.001).
  • [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
  • [Publication-type] Journal Article
  • [Publication-country] United States
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38. Lee SH, Lee MH, Lee JH, Min YH, Lee KH, Cheong JW, Lee J, Park KW, Kang JH, Kim K, Kim WS, Jung CW, Choi SJ, Lee JH, Park K: Infused CD34+ cell dose predicts long-term survival in acute myelogenous leukemia patients who received allogeneic bone marrow transplantation from matched sibling donors in first complete remission. Biol Blood Marrow Transplant; 2005 Feb;11(2):122-8
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  • [Title] Infused CD34+ cell dose predicts long-term survival in acute myelogenous leukemia patients who received allogeneic bone marrow transplantation from matched sibling donors in first complete remission.
  • Allogeneic stem cell transplantation (ASCT) has improved the outcome of acute myelogenous leukemia (AML).
  • To further improve the treatment outcome of ASCT in AML, finding a modifiable prognostic factor is mandatory.
  • We evaluated the effect of CD34(+) cell dose on survival in allogeneic bone marrow transplantation (BMT) from HLA-matched sibling donors for AML patients in first complete remission (CR1).
  • The high CD34(+) cell dose patients had better overall survival (5-year overall survival rate, 75% +/- 6% vs 52% +/- 9%; P = .01) and leukemia-free survival (5-year leukemia-free survival rate, 70% +/- 6% vs 44% +/- 9%; P = .04).
  • CD34(+) cell dose was the only independent prognostic factor in overall survival and leukemia-free survival.
  • The high CD34(+) cell dose group had a lower relapse incidence with a borderline statistical significance (5-year relapse rate, 27% +/- 6% vs 50% +/- 10%; P = .09).
  • There were no differences in the engraftment of neutrophil and platelet, grade II-IV acute graft-versus-host disease (GVHD), extensive-stage chronic GVHD, and transplant-related mortality between the high and low CD34(+) cell dose groups.
  • We confirmed that high CD34(+) cell dose favorably affects the outcomes in allogeneic BMT for AML.
  • The effort to attain a high CD34(+) cell dose should be pursued during bone marrow harvest in allogeneic BMT for AML in CR1.
  • [MeSH-major] Antigens, CD34 / analysis. Bone Marrow Cells / cytology. Bone Marrow Transplantation. Leukemia, Myeloid, Acute. Tissue Donors


39. Xu SX, Tang XH, Chen HQ, Feng B, Xu HQ, Chen XP, Tang XF: [Comparison of total body irradiation-cyclophosphamide versus busulphan-cyclophosphamide as conditioning regimens for myelogenous leukemia: a meta-analysis]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2008 Dec;16(6):1354-60
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  • [Title] [Comparison of total body irradiation-cyclophosphamide versus busulphan-cyclophosphamide as conditioning regimens for myelogenous leukemia: a meta-analysis].
  • Total body irradiation combined with cyclophosphamide (TBI/CY) and busulphan combined with cyclophosphamide (BU/CY) are standard conditioning regimens in hematological stem cell transplantation for patients with myelogenous leukemia.
  • This study was aimed to compare the therapeutic efficacy of TBI/CY and BU/CY as conditioning regiment for acute or chronic myelogenous leukemia.
  • Comparative studies were carried out on clinical therapeutic effects of TBI/CY and BU/CY including stem cell engraftment, relapse, complications, transplant-related mortality, and disease-free survival.
  • No significantly difference was found in engraftment failure and transplant-related mortality resulting from TBI/CY and BU/CY conditioning regimens, but the incidence of veno-occlusion of liver and hemorrhagic cystitis obviously increased in BU/CY group after transplantation, the acute GVHD, interstitial pneumonia and cataract significantly increased in TBI/CY group.
  • The relapse rate of AML in TBI/CY group was lower than that in BU/CY group, and the rate of long-term disease-free survival of AML patients in TBI/CY group also significantly lower than that in BU/CY group, but the relapse rate of CML in TBI/CY group after transplantation was obviously higher than that in BU/CY group, but there was no difference in longterm disease-free survival rate between the two conditioning regimens mentioned above.
  • It is concluded that the meta-analysis confirms different effects of TBI/CY and BU/CY regimens on myelogenous leukemia transplantation.

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  • (PMID = 19099643.001).
  • [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; Meta-Analysis
  • [Publication-country] China
  • [Chemical-registry-number] 8N3DW7272P / Cyclophosphamide; G1LN9045DK / Busulfan
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40. Ustün C, Kalla A, Bollag RJ, Manaloo E, Kulharya A, Jillella A: Relapsed acute myelogenous leukemia occurring after 18 years with recurrent novel chromosomal abnormality t(18;22)(q23;q11.2). Cancer Genet Cytogenet; 2007 Sep;177(2):135-8
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  • [Title] Relapsed acute myelogenous leukemia occurring after 18 years with recurrent novel chromosomal abnormality t(18;22)(q23;q11.2).
  • At age 4, she was diagnosed with acute myelogenous leukemia (AML) with t(18;22)(q23;q11.2) and received chemotherapy until age 6 under a pediatric study protocol.
  • The patient was treated for relapsed AML and at writing had been disease-free for 9 months.
  • Translocation between chromosomes 18 and 22 has been reported in indolent lymphoproliferative disorders, but not in AML.
  • Although we do not know the precise molecular etiology of this leukemia, the uncommon presentation for AML and late relapse with the same chromosomal abnormality may indicate a causal relationship between this novel chromosomal abnormality and the AML.
  • [MeSH-major] Chromosome Aberrations. Chromosomes, Human, Pair 18 / genetics. Chromosomes, Human, Pair 22 / genetics. Leukemia, Myeloid, Acute / genetics. Neoplasm Recurrence, Local / genetics

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  • (PMID = 17854669.001).
  • [ISSN] 0165-4608
  • [Journal-full-title] Cancer genetics and cytogenetics
  • [ISO-abbreviation] Cancer Genet. Cytogenet.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
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41. Nevill TJ, Hogge DE, Toze CL, Nantel SH, Power MM, Abou Mourad YR, Song KW, Lavoie JC, Forrest DL, Barnett MJ, Shepherd JD, Nitta JY, Wong S, Sutherland HJ, Smith CA: Predictors of outcome following myeloablative allo-SCT for therapy-related myelodysplastic syndrome and AML. Bone Marrow Transplant; 2008 Nov;42(10):659-66
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  • [Title] Predictors of outcome following myeloablative allo-SCT for therapy-related myelodysplastic syndrome and AML.
  • Administration of alkylating agents (Alk), topoisomerase II inhibitors (Topo II) and radiotherapy (RT) can result in therapy-related myelodysplastic syndrome or acute myelogenous leukaemia (t-MDS/t-AML), the optimal treatment for which is allo-SCT.
  • A retrospective review was performed of 24 patients who underwent related- or unrelated-donor SCT for t-MDS/t-AML at our institution.
  • Corresponding actuarial risks of relapse and non-relapse mortality (NRM) are 39% (19-60%) and 30% (13-50%), respectively.
  • EFS was 40% in Alk/RT-related t-MDS/t-AML and 11% in Topo II-related t-MDS/t-AML (P=0.05), with an increased risk of relapse in the latter (56 vs 29%, respectively (P=0.05)).
  • In multivariate analysis, development of acute GVHD (P=0.009) and Topo II-related t-MDS/t-AML (P=0.018) were associated with inferior EFS.
  • Patients with acute GVHD had an increased risk of NRM (P=0.03) whereas risk of relapse was higher for patients of advanced age (P=0.046) and for patients who underwent bone marrow (vs blood) SCT (P=0.032).
  • Allo-SCT can result in long-term survival for individuals with t-MDS/t-AML although outcome in Topo II-related t-MDS/t-AML patients remains suboptimal.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation. Leukemia, Myeloid, Acute / therapy. Myeloablative Agonists / adverse effects. Myelodysplastic Syndromes / therapy. Neoplasms, Second Primary / therapy


42. 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.
  • [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

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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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43. Fujiwara M, Satou N, Izumi N, Shibasaki Y, Higashimura M, Tsukada N, Koike T: [A short duration treatment with intensive consolidation therapy for patients with acute myelogenous leukemia--13 year experience in a single institute]. Gan To Kagaku Ryoho; 2007 Nov;34(11):1793-8
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  • [Title] [A short duration treatment with intensive consolidation therapy for patients with acute myelogenous leukemia--13 year experience in a single institute].
  • Fifty-seven patients with acute myelogenous leukemia (AML) received the following treatment in our hospital between May 1992 and April 2005.
  • Group A: combination of enocitabine, daunorubicin, 6-mercaptopurine riboside and prednisolone (BHAC-DMP) for remission induction, BHAC-DMP or idarubicin (IDR)+cytarabine (Ara-C) for first consolidation, combination of prednisolone, Ara-C, mitoxantrone and etoposide (PAME) for second consolidation, and PAME for late intensification; Group B: IDR+Ara-C for remission induction, PAME for first consolidation, and high-dose Ara-C+mitoxantrone for second consolidation; Group C (acute promyelocytic leukemia, APL) : all-trans retinoic acid (ATRA) for remission induction, BHAC-DMP or IDR+Ara-C for first consolidation, and PAME for second consolidation.
  • Five-year relapse-free survival rate of the CR patients was 35% in Group A, 49% in Group B, and 70% in Group C.
  • A short duration treatment with intensive consolidation therapy was effective for patients with AML and improved their quality of life (QOL).
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid, Acute / drug therapy

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  • (PMID = 18030012.001).
  • [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] 04079A1RDZ / Cytarabine; 5J49Q6B70F / Vincristine; 6PLQ3CP4P3 / Etoposide; 9PHQ9Y1OLM / Prednisolone; BZ114NVM5P / Mitoxantrone; E7WED276I5 / 6-Mercaptopurine; VB0R961HZT / Prednisone; ZRP63D75JW / Idarubicin; ZS7284E0ZP / Daunorubicin; BHAC-DMPV protocol; PAME protocol
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44. 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.
  • Forty-one patients were transplanted in complete remission (CR) (20 in CR1, 20 in CR2, and 1 in CR3), and 14 were not in remission at the time of transplantation as they were refractory to chemotherapy either at induction or at relapse.
  • Grade II-IV acute GVHD occurred in only 2 patients.
  • The 5-year cumulative incidence of relapse was 36% for the whole group and 28% for patients in CR at transplantation.
  • 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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45. Tamburini J, Elie C, Bardet V, Chapuis N, Park S, Broët P, Cornillet-Lefebvre P, Lioure B, Ugo V, Blanchet O, Ifrah N, Witz F, Dreyfus F, Mayeux P, Lacombe C, Bouscary D: Constitutive phosphoinositide 3-kinase/Akt activation represents a favorable prognostic factor in de novo acute myelogenous leukemia patients. Blood; 2007 Aug 1;110(3):1025-8
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Constitutive phosphoinositide 3-kinase/Akt activation represents a favorable prognostic factor in de novo acute myelogenous leukemia patients.
  • The phosphoinositide 3-kinase (PI3K/Akt) pathway is activated in acute myelogenous leukemia (AML) and is promising for targeted inhibition.
  • Ninety-two patients with primary AML were analyzed for PI3K/Akt constitutive activation.
  • With a median follow-up of 26 months, we observed for PI3K (+) and PI3K (-) patients, respectively, 56% and 33% overall survival (P = .001) and 72% and 41% relapse-free survival (P = .001).
  • Constitutive PI3K/Akt activity is a favorable prognosis factor in AML, even after adjustment for FLT3-ITD, and may confer a particular sensitivity to chemotherapy.
  • A better understanding of the downstream effectors of the PI3K/Akt pathway is needed before targeting in AML.
  • [MeSH-major] Blast Crisis / enzymology. Leukemia, Myeloid, Acute / enzymology. Phosphatidylinositol 3-Kinases / metabolism. Proto-Oncogene Proteins c-akt / metabolism


46. Winer ES, Miller KB, Chan GW: GM-CSF and low-dose cytosine arabinoside in high-risk, elderly patients with AML or MDS. Oncology (Williston Park); 2005 Apr;19(4 Suppl 2):11-4
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  • [Title] GM-CSF and low-dose cytosine arabinoside in high-risk, elderly patients with AML or MDS.
  • In this study, we utilized these synergistic effects of granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim [Leukine]), hydroxyurea, and low-dose cytosine arabinoside to treat elderly patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS).
  • In a single-institution, retrospective study, we evaluated 94 treatments with concomitant hydroxyurea, cytosine arabinoside, and GM-CSF between the years of 1997 and 2003 in high-risk elderly patients with AML or MDS.
  • Twenty-one percent of patients remained neutropenic after treatment until death or relapse.
  • Overall, our study showed that low-dose cytosine arabinoside given by continuous infusion together with continuous infusion GM-CSF and hydroxyurea was well-tolerated and effective in treating elderly AML and MDS patients who were not eligible for standard induction therapy.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cytarabine / administration & dosage. Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage. Leukemia, Myeloid, Acute / drug therapy. Myelodysplastic Syndromes / drug therapy

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  • (PMID = 15934494.001).
  • [ISSN] 0890-9091
  • [Journal-full-title] Oncology (Williston Park, N.Y.)
  • [ISO-abbreviation] Oncology (Williston Park, N.Y.)
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 0 / Recombinant Proteins; 04079A1RDZ / Cytarabine; 83869-56-1 / Granulocyte-Macrophage Colony-Stimulating Factor; X6Q56QN5QC / Hydroxyurea
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47. Kim HJ, Min WS, Cho BS, Eom KS, Kim YJ, Min CK, Lee S, Cho SG, Jin JY, Lee JW, Kim CC: Successful prevention of acute graft-versus-host disease using low-dose antithymocyte globulin after mismatched, unrelated, hematopoietic stem cell transplantation for acute myelogenous leukemia. Biol Blood Marrow Transplant; 2009 Jun;15(6):704-17
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  • [Title] Successful prevention of acute graft-versus-host disease using low-dose antithymocyte globulin after mismatched, unrelated, hematopoietic stem cell transplantation for acute myelogenous leukemia.
  • In this study, we investigated the effects of low-dose antithymocyte globulin (ATG, thymoglobulin) in the prevention of acute graft-versus-host disease (aGVHD) in mismatched, unrelated hematopoietic stem cell transplantations (uHSCTs) in patients with the single disease entity of acute myelogenous leukemia (AML).
  • Patients (n = 103) with a variable risk for AML who received uHSCTs from available Asian and Caucasian donors were enrolled.
  • These results suggest that in mismatched uHSCT, a low dose of ATG (total 2.5 mg/kg) may prevent moderate to severe aGVHD, with comparable rates of relapse and CMV reactivation and a greatly decreased rate of NRM.
  • [MeSH-major] Antilymphocyte Serum / therapeutic use. Graft vs Host Disease / prevention & control. Hematopoietic Stem Cell Transplantation / adverse effects. Leukemia, Myeloid / surgery
  • [MeSH-minor] Acute Disease. Adolescent. Adult. Chronic Disease. Disease-Free Survival. Female. HLA Antigens / analysis. Histocompatibility. Humans. Incidence. Living Donors. Male. Methotrexate / administration & dosage. Middle Aged. Prospective Studies. Survival Analysis. T-Lymphocytes / immunology. Tacrolimus / administration & dosage. Transplantation Conditioning. Transplantation, Homologous / adverse effects. Young Adult

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  • (PMID = 19450755.001).
  • [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
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antilymphocyte Serum; 0 / HLA Antigens; WM0HAQ4WNM / Tacrolimus; YL5FZ2Y5U1 / Methotrexate
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48. Nimer SD: Is it important to decipher the heterogeneity of "normal karyotype AML"? Best Pract Res Clin Haematol; 2008 Mar;21(1):43-52
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  • [Title] Is it important to decipher the heterogeneity of "normal karyotype AML"?
  • Almost half of adult acute myelogenous leukemia (AML) is normal cytogenetically, and this subgroup shows a remarkable heterogeneity of genetic mutations at the molecular level and an intermediate response to therapy.
  • Yet "normal karyotype AML" lacks such obvious abnormalities, but has a variety of prognostically important genetic abnormalities.
  • Thus, the presence of a FLT3-ITD (internal tandem duplication), MLL-PTD (partial tandem duplication), or the increased expression of ERG or EVI1 mRNAs confer a poor prognosis, and an increased risk of relapse.
  • In contrast, the presence of cytoplasmic nucleophosmin or C/EBPA mutations is associated with lower relapse rates and improved survival.
  • Although resistance to treatment is associated with specific mutations, the degree to which the leukemia resembles a stem cell in its functional properties may provide greater protection from the effects of treatment.
  • Although usually all of the circulating leukemia cells are cleared following treatment, a small residual population of leukemic cells in the bone marrow persists, making this disease hard to eradicate.
  • Increased understanding of the biological consequences of at least some of these mutations in "normal karyotype AML" is leading to more targeted approaches to develop more effective treatments for this disease.

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  • (PMID = 18342811.001).
  • [ISSN] 1521-6926
  • [Journal-full-title] Best practice & research. Clinical haematology
  • [ISO-abbreviation] Best Pract Res Clin Haematol
  • [Language] ENG
  • [Grant] United States / NIDDK NIH HHS / DK / R01 DK052621; United States / NIDDK NIH HHS / DK / R01 DK052621-08; United States / NIDDK NIH HHS / DK / R56 DK052208-09A1; United States / NCI NIH HHS / CA / R01 CA102202-01; United States / NCI NIH HHS / CA / CA102202-01; United States / NIDDK NIH HHS / DK / R56 DK052208; United States / NCI NIH HHS / CA / R01 CA102202; United States / NIDDK NIH HHS / DK / DK052208-09A1; United States / NIDDK NIH HHS / DK / DK052621-08
  • [Publication-type] Journal Article; Review
  • [Publication-country] Netherlands
  • [Number-of-references] 76
  • [Other-IDs] NLM/ NIHMS44325; NLM/ PMC2654590
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49. Karp JE, Smith BD, Gojo I, Lancet JE, Greer J, Klein M, Morris L, Levis MJ, Gore SD, Wright JJ, Garrett-Mayer E: Phase II trial of tipifarnib as maintenance therapy in first complete remission in adults with acute myelogenous leukemia and poor-risk features. Clin Cancer Res; 2008 May 15;14(10):3077-82
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Phase II trial of tipifarnib as maintenance therapy in first complete remission in adults with acute myelogenous leukemia and poor-risk features.
  • PURPOSE: Acute myelogenous leukemia (AML) does not have a high cure rate, particularly in patients with poor-risk features.
  • Tipifarnib is an oral farnesyltransferase inhibitor with activity in AML.
  • We conducted a phase II trial of maintenance tipifarnib monotherapy for 48 adults with poor-risk AML in first CR.
  • RESULTS: Twenty (42%) patients completed 16 cycles, 24 (50%) were removed from study for relapse, and 4 (8%) discontinued drug prematurely for intolerance.
  • Comparison of CR durations for 25 patients who received two-cycle timed sequential therapy followed by tipifarnib maintenance with 23 historically similar patients who did not receive tipifarnib showed that tipifarnib was associated with DFS prolongation for patients with secondary AML and adverse cytogenetics.
  • CONCLUSIONS: This study suggests that some patients with poor-risk AML, including patients with secondary AML and adverse cytogenetics, may benefit from tipifarnib maintenance therapy.

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  • (PMID = 18483374.001).
  • [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 / CA 69854; United States / NCI NIH HHS / CA / U01 CA069854-07; United States / NCI NIH HHS / CA / U01 CA069854; United States / NCI NIH HHS / CA / U01 CA70095; United States / NCI NIH HHS / CA / U01 CA070095
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Quinolones; 192185-72-1 / tipifarnib
  • [Other-IDs] NLM/ NIHMS281726; NLM/ PMC3074480
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50. Dawczynski K, Steinbach D, Wittig S, Pfaffendorf N, Kauf E, Zintl F: Expression of components of the IGF axis in childhood acute myelogenous leukemia. Pediatr Blood Cancer; 2008 Jan;50(1):24-8
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  • [Title] Expression of components of the IGF axis in childhood acute myelogenous leukemia.
  • PROCEDURE: We analyzed the mRNA expression profile of IGF-I, -II, and IGFBP-2, -3 in 50 children with previously untreated AML (mean age 10.8 +/- 4.8 years; patients in CCR n = 20, patients with relapse during later course of disease n = 15).
  • RESULTS: IGFBP-2 expression was significantly higher in AML cells than in healthy cells of peripheral MNC (P < 0.001) and of bone marrow cells (P < 0.01).
  • Conversely, AML cells showed significantly lower IGFBP-3 and IGF-I gene expression compared to controls (P = 0.02; P < 0.001).
  • Patients with relapse (median +/- range: 0.0929 +/- 0.049) during later course of disease demonstrated higher IGFBP-2 expression compared to patients in CCR (0.0121 +/- 0.047; P = 0.06) at time of diagnosis.
  • A multivariate analysis identified the IGFBP-2 mRNA expression as an independent factor for the prediction of relapse.
  • Furthermore, the probability of relapse-free survival (RFS) in patients with IGFBP-2 mRNA level >0.1000 was 28%; whereas, the probability of RFS in patients with IGFBP-2 mRNA level <0.1000 was 62% (P = 0.04, log-rank test).
  • CONCLUSIONS: Results identified different expressions of IGF components between normal and AML cells.
  • Patients with IGFBP-2 mRNA levels up to 0.1000 (relative to KG1 cell line) more likely developed a relapse.
  • Identification of these patients at diagnosis may allow more individualized treatment.
  • [MeSH-major] Insulin-Like Growth Factor Binding Protein 2 / metabolism. Insulin-Like Growth Factor Binding Protein 3 / metabolism. Insulin-Like Growth Factor I / metabolism. Insulin-Like Growth Factor II / metabolism. Leukemia, Myeloid, Acute / metabolism

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  • [Copyright] (c) 2007 Wiley-Liss, Inc.
  • (PMID = 17635002.001).
  • [ISSN] 1545-5017
  • [Journal-full-title] Pediatric blood & cancer
  • [ISO-abbreviation] Pediatr Blood Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Insulin-Like Growth Factor Binding Protein 2; 0 / Insulin-Like Growth Factor Binding Protein 3; 0 / RNA, Messenger; 67763-96-6 / Insulin-Like Growth Factor I; 67763-97-7 / Insulin-Like Growth Factor II
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51. Molnár I, Powell BL: What role does gemtuzumab ozogamicin have in the treatment of acute myelogenous leukemia? Curr Hematol Malig Rep; 2007 May;2(2):104-10
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] What role does gemtuzumab ozogamicin have in the treatment of acute myelogenous leukemia?
  • Gemtuzumab ozogamicin (GO) is a novel, targeted chemotherapy designed to treat acute myeloid leukemia (AML).
  • It has been approved in the United States since 2000 to treat CD33+ AML in first relapse in older adults who are not candidates for cytotoxic therapy.
  • Single-agent GO has a limited role in de novo AML.
  • Incorporation of GO into standard induction treatment in de novo and relapsed AML is feasible.
  • [MeSH-major] Aminoglycosides / therapeutic use. Antibiotics, Antineoplastic / therapeutic use. Antibodies, Monoclonal / therapeutic use. Immunotoxins / therapeutic use. Leukemia, Myeloid, Acute / drug therapy

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  • (PMID = 20425358.001).
  • [ISSN] 1558-822X
  • [Journal-full-title] Current hematologic malignancy reports
  • [ISO-abbreviation] Curr Hematol Malig Rep
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Aminoglycosides; 0 / Antibiotics, Antineoplastic; 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antigens, CD; 0 / Antigens, Differentiation, Myelomonocytic; 0 / CD33 protein, human; 0 / Immunotoxins; 0 / Sialic Acid Binding Ig-like Lectin 3; 0 / gemtuzumab
  • [Number-of-references] 50
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52. Cammenga J, Horn S, Bergholz U, Sommer G, Besmer P, Fiedler W, Stocking C: Extracellular KIT receptor mutants, commonly found in core binding factor AML, are constitutively active and respond to imatinib mesylate. Blood; 2005 Dec 1;106(12):3958-61
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  • [Title] Extracellular KIT receptor mutants, commonly found in core binding factor AML, are constitutively active and respond to imatinib mesylate.
  • Multiple genetic alterations are required to induce acute myelogenous leukemia (AML).
  • Mutations in the extracellular domain of the KIT receptor are almost exclusively found in patients with AML carrying translocations or inversions affecting members of the core binding factor (CBF) gene family and correlate with a high risk of relapse.
  • Our data show that the addition of kinase inhibitors to conventional chemotherapy might be a new therapeutic option for CBF-AML expressing mutant KIT.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Core Binding Factors / genetics. Leukemia, Myeloid, Acute / genetics. Piperazines / pharmacology. Pyrimidines / pharmacology. Stem Cell Factor / genetics

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  • (PMID = 16081693.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Core Binding Factors; 0 / Piperazines; 0 / Pyrimidines; 0 / Stem Cell Factor; 8A1O1M485B / Imatinib Mesylate
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53. Stone RM, DeAngelo DJ, Janosova A, Galinsky I, Canning C, Ritz J, Soiffer RJ: Low dose interleukin-2 following intensification therapy with high dose cytarabine for acute myelogenous leukemia in first complete remission. Am J Hematol; 2008 Oct;83(10):771-7
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  • [Title] Low dose interleukin-2 following intensification therapy with high dose cytarabine for acute myelogenous leukemia in first complete remission.
  • The most important problem in the therapy of patients with acute myeloid leukemia (AML) is relapse after intensive therapy.
  • Adults with de novo AML received daunorubicin and cytosine arabinoside induction therapy.
  • Mononuclear cells from patients receiving rIL-2 exhibited enhanced cytolytic activity in vitro against cryopreserved autologous leukemia cells.
  • This study supports further investigation of immunotherapy in the post-intensive chemotherapy setting in the management of patients with AML.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid / drug therapy
  • [MeSH-minor] Acute Disease. Adult. Aged. Clinical Trials as Topic. Cytarabine / administration & dosage. Cytarabine / adverse effects. Dose-Response Relationship, Drug. Fatigue / chemically induced. Feasibility Studies. Female. Fever / chemically induced. Follow-Up Studies. Humans. Interleukin-2 / administration & dosage. Interleukin-2 / genetics. Killer Cells, Natural / drug effects. Male. Middle Aged. Recombinant Proteins / administration & dosage. Recombinant Proteins / adverse effects. Remission Induction. Survival Analysis. T-Lymphocytes / drug effects. Thrombocytopenia / chemically induced. Time Factors. Treatment Outcome

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  • [Copyright] Copyright 2008 Wiley-Liss, Inc.
  • (PMID = 18756547.001).
  • [ISSN] 1096-8652
  • [Journal-full-title] American journal of hematology
  • [ISO-abbreviation] Am. J. Hematol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA66996
  • [Publication-type] Clinical Trial; Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Interleukin-2; 0 / Recombinant Proteins; 04079A1RDZ / Cytarabine
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54. Karp JE, Smith BD, Levis MJ, Gore SD, Greer J, Hattenburg C, Briel J, Jones RJ, Wright JJ, Colevas AD: Sequential flavopiridol, cytosine arabinoside, and mitoxantrone: a phase II trial in adults with poor-risk acute myelogenous leukemia. Clin Cancer Res; 2007 Aug 1;13(15 Pt 1):4467-73
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  • [Title] Sequential flavopiridol, cytosine arabinoside, and mitoxantrone: a phase II trial in adults with poor-risk acute myelogenous leukemia.
  • In a phase I study of flavopiridol followed by 1-beta-d-arabinofuranosylcytosine (ara-C) and mitoxantrone, overall response rate for adults with relapsed and refractory acute myelogenous leukemias (AML) was 31%.
  • We have now completed a phase II study of sequential flavopiridol, ara-C, and mitoxantrone in 62 adults with poor-risk AML.
  • Complete remissions (CR) were achieved in 12 of 15 (75%) newly diagnosed secondary AML, 18 of 24 (75%) first relapse after short CR (median CR, 9 months, including prior allotransplant), and 2 of 13 (15%) primary refractory but 0 of 10 multiply refractory AML.
  • CONCLUSIONS: Flavopiridol has anti-AML activity directly and in combination with ara-C and mitoxantrone.
  • This timed sequential regimen induces durable CRs in a significant proportion of adults with newly diagnosed secondary AML (including complex cytogenetics) and adults with AML in first relapse after short first CR.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid, Acute / drug therapy

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  • (PMID = 17671131.001).
  • [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 / NCRR NIH HHS / RR / M01-RR0052; United States / NCI NIH HHS / CA / U01 CA70095
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Flavonoids; 0 / Piperidines; 04079A1RDZ / Cytarabine; 45AD6X575G / alvocidib; BZ114NVM5P / Mitoxantrone
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55. 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.
  • Data regarding disease characteristics at diagnosis and relapse, treatment response, and survival was collected on 99 patients and 164 medullary relapses or treatment failures.
  • [MeSH-major] Leukemia, Myeloid, Acute / drug therapy

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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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56. Kikushige Y, Takase K, Miyamoto T, Numata A, Kamesaki K, Fukuda T, Nagafuji K, Gondo H, Harada M: Late relapse of acute myelogenous leukemia followed by epstein-barr virus-associated lymphoproliferative disease 11 years after allogeneic bone marrow transplantation. Int J Hematol; 2006 Dec;84(5):441-4
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  • [Title] Late relapse of acute myelogenous leukemia followed by epstein-barr virus-associated lymphoproliferative disease 11 years after allogeneic bone marrow transplantation.
  • Allogeneic hematopoietic stem cell transplantation (allo-HSCT) following myeloablative conditioning represents the treatment of choice for patients with chemotherapy-resistant leukemia.
  • We describe a 49-year-old man with advanced, refractory acute myelogenous leukemia (AML) that was treated successfully by allogeneic bone marrow transplantation from a sibling donor with HLA mismatched at 1 locus.
  • AML relapse was documented 11 years after transplantation.
  • As a result, immune surveillance against remaining quiescent leukemic cells as well as viral infection may have been defective, leading to the relapse of leukemia and EBV-associated PTLD.
  • [MeSH-major] Bone Marrow Transplantation. Epstein-Barr Virus Infections. Herpesvirus 4, Human. Leukemia, Myeloid, Acute


57. Aoki T, Miyamoto T, Yoshida S, Yamamoto A, Yamauchi T, Yoshimoto G, Mori Y, Kamezaki K, Iwasaki H, Takenaka K, Harada N, Nagafuji K, Teshima T, Akashi K: Additional acquisition of t(1;21)(p32;q22) in a patient relapsing with acute myelogenous leukemia with NUP98-HOXA9. Int J Hematol; 2008 Dec;88(5):571-4
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  • [Title] Additional acquisition of t(1;21)(p32;q22) in a patient relapsing with acute myelogenous leukemia with NUP98-HOXA9.
  • We report a 29-year-old Japanese male with acute myelogenous leukemia (AML)-M4 with a cryptic t(7;11)(p15;p15), in which a chimeric NUP98-HOXA9 fusion was detected by polymerase chain reaction analysis and a chromosomal analysis showed 46,XY.
  • This is the first reported case with AML who had a cryptic t(7;11)(p15;p15), and additionally acquired t(1;21)(p32;q22) at relapse.
  • [MeSH-major] Chromosomes, Human / genetics. Core Binding Factor Alpha 2 Subunit / genetics. Homeodomain Proteins / genetics. Leukemia, Myeloid, Acute / genetics. Leukemia, Myeloid, Acute / therapy. Nuclear Pore Complex Proteins / genetics. Oncogene Proteins, Fusion / genetics. Translocation, Genetic

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  • (PMID = 19005624.001).
  • [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 / AML1-ETO fusion protein, human; 0 / Core Binding Factor Alpha 2 Subunit; 0 / Homeodomain Proteins; 0 / NUP98-HOXA9 fusion protein, human; 0 / Nuclear Pore Complex Proteins; 0 / Oncogene Proteins, Fusion
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58. Sisler IY, Koehler E, Koyama T, Domm JA, Ryan R, Levine JE, Pulsipher MA, Haut PR, Schultz KR, Taylor DS, Frangoul HA: Impact of conditioning regimen in allogeneic hematopoetic stem cell transplantation for children with acute myelogenous leukemia beyond first complete remission: a pediatric blood and marrow transplant consortium (PBMTC) study. Biol Blood Marrow Transplant; 2009 Dec;15(12):1620-7
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  • [Title] Impact of conditioning regimen in allogeneic hematopoetic stem cell transplantation for children with acute myelogenous leukemia beyond first complete remission: a pediatric blood and marrow transplant consortium (PBMTC) study.
  • Total body irradiation (TBI)-based conditioning regimens for pediatric patients with acute myelogenous leukemia (AML) beyond first complete remission (CR1) are controversial.
  • We retrospectively evaluated 151 pediatric patients with AML beyond CR1, comparing outcomes in 90 patients who received a TBI-based conditioning regimen and 61 patients who received a Bu-based conditioning regimen.
  • The probability of relapse at 2 years also did not differ between the 2 groups (26% and 27%, respectively; P=.93).
  • Our study provides no evidence of an advantage to using TBI in children with AML beyond CR1.
  • [MeSH-major] Antineoplastic Agents, Alkylating / therapeutic use. Busulfan / therapeutic use. Hematopoietic Stem Cell Transplantation / methods. Leukemia, Myeloid, Acute / therapy. Transplantation Conditioning / methods

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  • (PMID = 19896086.001).
  • [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
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; G1LN9045DK / Busulfan
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59. Harned TM, Gaynon PS: Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag; 2008 Apr;4(2):327-36
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  • Approximately 4000 children and adolescents under the age of 20 years develop acute leukemia per year in the US.
  • Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer.
  • Therapy for relapsed ALL remains unsatisfactory, and the majority of relapse patients still succumb to leukemia.
  • Between one-third and one-half of patients with acute myelogenous leukemia (AML) relapse, and no standard therapy is recognized for patients with relapsed and/or refractory AML.
  • Novel therapeutic agents are needed to improve the cure rate for relapsed ALL and AML.
  • Phase I and II single-agent trials in children have shown that clofarabine is safe and active in both myeloid and lymphoid relapsed/refractory acute leukemias.

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  • (PMID = 18728851.001).
  • [ISSN] 1176-6336
  • [Journal-full-title] Therapeutics and clinical risk management
  • [ISO-abbreviation] Ther Clin Risk Manag
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] New Zealand
  • [Other-IDs] NLM/ PMC2504075
  • [Keywords] NOTNLM ; childhood / clofarabine / leukemia / pediatric / refractory
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60. Afzal S, Ishaqi MK, Dupuis A, Doyle J, Gassas A: Early lymphocyte recovery after allogeneic hematopoietic SCT is associated with significant GVL effect in pediatric ALL but not acute myelogenous leukemia-Update study. Bone Marrow Transplant; 2009 Dec;44(12):799-804
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  • [Title] Early lymphocyte recovery after allogeneic hematopoietic SCT is associated with significant GVL effect in pediatric ALL but not acute myelogenous leukemia-Update study.
  • To answer the question whether this is true for AML, we extended our cohort to 207 consecutive children with acute leukemia by adding 71 children with AML who received 75 HSCT's between 1994 and 2005.
  • For the AML cohort, all patients at time of HSCT were in complete morphological remission (CR) except for one patient in CR1, who had 8% blasts in the BM before HSCT.
  • In AML, absolute lymphocyte count <0.3 x 10(9)/l or >0.3 x 10(9)/l on days 21 and 30 were not predictive of relapse with a hazard ratio at day 21=0.88; P=0.8, and hazard ratio at day 30=0.5; P=0.2.
  • [MeSH-major] Graft vs Leukemia Effect. Hematopoietic Stem Cell Transplantation. Leukemia, Myeloid, Acute / blood. Leukemia, Myeloid, Acute / therapy. Lymphocytes. Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy. Recovery of Function

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  • (PMID = 19421173.001).
  • [ISSN] 1476-5365
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Publication-type] Clinical Trial; Comparative Study; Journal Article
  • [Publication-country] England
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61. Kara IO, Sahin B, Paydas S, Kara B: Granulocytic sarcoma of the heart: extramedullary relapse of acute myeloblastic leukemia after allogeneic stem cell transplantation successfully treated by chemotherapy alone. Leuk Lymphoma; 2005 Jul;46(7):1081-4
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  • [Title] Granulocytic sarcoma of the heart: extramedullary relapse of acute myeloblastic leukemia after allogeneic stem cell transplantation successfully treated by chemotherapy alone.
  • A 28-year-old man with relapsed acute myelogenous leukemia (AML-M2) had undergone a non-myeloablative allogeneic peripheral stem cell transplantation.
  • Three years following transplantation, masses were evidenced in his heart by echocardiography but had completely disappeared following a common chemotherapy etoposide, mitoxantrone, ara-C (EMA) regimen for relapsed AML.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid, Acute / therapy. Peripheral Blood Stem Cell Transplantation / adverse effects. Sarcoma, Myeloid / drug therapy. Sarcoma, Myeloid / etiology
  • [MeSH-minor] Adult. Cytarabine / administration & dosage. Etoposide / administration & dosage. Heart Neoplasms / diagnosis. Heart Neoplasms / drug therapy. Heart Neoplasms / etiology. Humans. Male. Mitoxantrone / administration & dosage. Neoplasm Recurrence, Local / drug therapy. Remission Induction. Transplantation, Homologous

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  • (PMID = 16019562.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 6PLQ3CP4P3 / Etoposide; BZ114NVM5P / Mitoxantrone
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62. Armand P, Kim HT, DeAngelo DJ, Ho VT, Cutler CS, Stone RM, Ritz J, Alyea EP, Antin JH, Soiffer RJ: Impact of cytogenetics on outcome of de novo and therapy-related AML and MDS after allogeneic transplantation. Biol Blood Marrow Transplant; 2007 Jun;13(6):655-64
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  • [Title] Impact of cytogenetics on outcome of de novo and therapy-related AML and MDS after allogeneic transplantation.
  • Cytogenetics has an important impact on the prognosis of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS).
  • In this study, we retrospectively analyzed data on 556 patients with AML or MDS transplanted at our institution.
  • We examined, in multivariate analyses, the contribution of cytogenetics to survival, relapse, and nonrelapse mortality for the 476 patients with de novo disease.
  • When classified by this new scheme, cytogenetics was the strongest prognostic factor for overall survival in our cohort, through its impact on the risk of relapse (and not on nonrelapse mortality).
  • After accounting for cytogenetics, patients with therapy-related AML or MDS had an equivalent outcome to those with de novo disease.
  • This study demonstrates the impact of cytogenetics on the risk of relapse and death for patients with both de novo and therapy-related disease undergoing transplantation; it also emphasizes the necessity of using cytogenetics to stratify patients entering clinical trials, and provides a system for doing so, which can be validated in a multi-institutional database.

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  • (PMID = 17531775.001).
  • [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
  • [Grant] United States / NIAID NIH HHS / AI / U19 AI029530-14; United States / NIAID NIH HHS / AI / U19 AI 29530; United States / NHLBI NIH HHS / HL / P01 HL070149; United States / NCI NIH HHS / CA / T32 CA009172; United States / NIAID NIH HHS / AI / AI029530-14; United States / NHLBI NIH HHS / HL / P01 HL 070149; United States / NIAID NIH HHS / AI / U19 AI029530
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Other-IDs] NLM/ NIHMS25237; NLM/ PMC2743535
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63. Bhatla D, Gerbing RB, Alonzo TA, Mehta PA, Deal K, Elliott J, Meshinchi S, Geiger H, Perentesis JP, Lange BJ, Davies SM, Children's Oncology Group: DNA repair polymorphisms and outcome of chemotherapy for acute myelogenous leukemia: a report from the Children's Oncology Group. Leukemia; 2008 Feb;22(2):265-72
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  • [Title] DNA repair polymorphisms and outcome of chemotherapy for acute myelogenous leukemia: a report from the Children's Oncology Group.
  • Polymorphisms of DNA repair genes RAD51 and XRCC3 increase susceptibility to acute myeloid leukemia (AML) in adults, an effect enhanced by deletion of the glutathione-S-transferase M1 (GSTM1) gene.
  • In this study, we genotyped 452 children with de novo AML treated on CCG protocols 2941 and 2961 and compared genotype frequencies with those of normal blood donors, and analyzed the impact of genotype on outcome of therapy.
  • XRCC3 Thr241Met, RAD51 G135C and GSTM1 genotypes did not increase susceptibility to AML when assessed singly.
  • In contrast, when XRCC3 and RAD51 genotypes were examined together a significant increase in susceptibility to AML was seen in children with variant alleles.
  • Improved survival was due to reduced relapse in the heterozygous children, and this effect was most marked in children randomized to therapy likely to generate DNA double-strand breaks (etoposide, daunomycin), compared with anti-metabolite (fludarabine, cytarabine) based therapy.
  • In contrast, RAD51 G135C and the GSTM1 deletion polymorphism did not influence outcome of AML therapy in our study population.

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  • (PMID = 18033323.001).
  • [ISSN] 1476-5551
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R21 CA10262-01; United States / NCI NIH HHS / CA / R01 CA093552-01; United States / NCI NIH HHS / CA / CA 98543; United States / NCI NIH HHS / CA / R01 CA114563-01; United States / NCI NIH HHS / CA / R01CA93552-01; United States / NCI NIH HHS / CA / R01 CA093552; United States / NCI NIH HHS / CA / R01 CA114563; United States / NCI NIH HHS / CA / U10 CA098543; United States / NCI NIH HHS / CA / CA093552-01
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / DNA-Binding Proteins; 0 / X-ray repair cross complementing protein 3; EC 2.7.7.- / Rad51 Recombinase
  • [Other-IDs] NLM/ NIHMS210453; NLM/ PMC2914507
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64. Stringaris K, Adams S, Uribe M, Eniafe R, Wu CO, Savani BN, Barrett AJ: Donor KIR Genes 2DL5A, 2DS1 and 3DS1 are associated with a reduced rate of leukemia relapse after HLA-identical sibling stem cell transplantation for acute myeloid leukemia but not other hematologic malignancies. Biol Blood Marrow Transplant; 2010 Sep;16(9):1257-64
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  • [Title] Donor KIR Genes 2DL5A, 2DS1 and 3DS1 are associated with a reduced rate of leukemia relapse after HLA-identical sibling stem cell transplantation for acute myeloid leukemia but not other hematologic malignancies.
  • Elimination of malignant cells through a graft-versus-leukemia (GVL) effect involves donor T and natural killer (NK) cells, but their relative contribution to this process is poorly defined.
  • We performed KIR-genotyping of HLA-identical sibling donors in 246 T cell-depleted SCTs to identify genetic factors affecting transplant outcome (treatment-related mortality [TRM], leukemic relapse, and survival).
  • Univariate and multivariate analysis of transplant-related risk factors and KIR genotyping was performed to identify independent variables predictive of outcome for different forms of leukemia.
  • Further to confirming known predictive factors for TRM and survival (CD34 cell dose, patient age, disease stage), statistical analysis revealed that 3 donor B haplotype KIR genes, 2DL5A, 2DS1, and 3DS1, were associated with significantly less relapse in patients with acute myelogenous leukemia (AML) (13% versus 57%) but not in patients with other myelogenous or lymphoid malignancies.
  • AML patients receiving SCT from donors with these KIR genes relapsed 4 times less frequently than patients transplanted from donors with other KIR genotypes.
  • These findings suggest specific, genetically determined, interactions between NK cells and AML cells that facilitate the GVL effect, and have implications for donor selection for AML patients.
  • [MeSH-major] HLA Antigens / immunology. Hematologic Neoplasms / genetics. Hematologic Neoplasms / therapy. Leukemia, Myeloid, Acute / genetics. Leukemia, Myeloid, Acute / therapy. Receptors, KIR / genetics. Stem Cell Transplantation / methods

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  • [Copyright] Published by Elsevier Inc.
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  • (PMID = 20302958.001).
  • [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 / Intramural NIH HHS / / ZIA HL006105-02
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / HLA Antigens; 0 / Receptors, KIR
  • [Other-IDs] NLM/ NIHMS207885; NLM/ PMC3801172
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65. 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

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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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66. Kotzerke J, Bunjes D, Scheinberg DA: Radioimmunoconjugates in acute leukemia treatment: the future is radiant. Bone Marrow Transplant; 2005 Dec;36(12):1021-6
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  • [Title] Radioimmunoconjugates in acute leukemia treatment: the future is radiant.
  • Targeted radiotherapy of the bone marrow using radiolabeled monoclonal antibodies is a therapeutic approach of considerable potential for the treatment of acute leukemia in addition to or as a substitute for total body irradiation.
  • The data currently available, of about 300 patients, suggest that radioimmunotherapy (RIT) with beta-emitters in acute leukemia is feasible and safe using a variety of antibodies (anti-CD33, anti-CD45, anti-CD66) and radionuclides (131I, 90Y, 188Re).
  • It appears to reduce the risk of relapse in high-risk acute myelogenous leukemia (AML) patients transplanted early in the course of their disease (<15% blasts) to 20-30%.
  • Furthermore, it has shown the potential to safely intensify reduced-intensity conditioning regimens (nonrelapse mortality of 25% compared to relapse rate of 55% within 2 years).
  • Significant improvements in the results of refractory patients will probably depend on the successful further development of RIT with alpha-emitters or the use of a cocktail of antibodies labeled with alpha- and beta-emitters, in a first dose escalation study of 213Bi-labeled anti-CD33 in refractory AML (partial) remission could be achieved in 5/18 patients.
  • [MeSH-major] Immunoconjugates / therapeutic use. Leukemia / radiotherapy

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  • (PMID = 16247432.001).
  • [ISSN] 0268-3369
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antigens, CD; 0 / Antigens, Differentiation, Myelomonocytic; 0 / CD33 protein, human; 0 / CD66 antigens; 0 / Cell Adhesion Molecules; 0 / Immunoconjugates; 0 / Radioisotopes; 0 / Sialic Acid Binding Ig-like Lectin 3; 0 / Yttrium Radioisotopes; 7440-15-5 / Rhenium; EC 3.1.3.48 / Antigens, CD45
  • [Number-of-references] 38
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67. Kornblau SM, Qiu YH, Bekele BN, Cade JS, Zhou X, Harris D, Jackson CE, Estrov Z, Andreeff M: Studying the right cell in acute myelogenous leukemia: dynamic changes of apoptosis and signal transduction pathway protein expression in chemotherapy resistant ex-vivo selected "survivor cells". Cell Cycle; 2006 Dec;5(23):2769-77
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  • [Title] Studying the right cell in acute myelogenous leukemia: dynamic changes of apoptosis and signal transduction pathway protein expression in chemotherapy resistant ex-vivo selected "survivor cells".
  • We hypothesized that studying protein expression in cells surviving in vitro chemotherapy ("survivor cells", SV), could provide more important insight into the biology of drug-resistant AML cells than analysis of the bulk population of leukemic cells.
  • Leukemia-enriched samples from 79 patients with new or relapsed AML were cultured for four days +/- cytarabine (5-10 microM).
  • The patterns of change were highly predictive of remission attainment, relapse, and survival in univariate and multivariate analysis.
  • Analysis of SV cells may be more informative than analysis of the bulk population of leukemia cells.
  • [MeSH-major] Apoptosis. Drug Resistance, Neoplasm. Leukemia, Myeloid, Acute / pathology. Leukemia, Myeloid, Acute / therapy. Neoplasm Proteins / metabolism. Signal Transduction

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  • (PMID = 17172852.001).
  • [ISSN] 1551-4005
  • [Journal-full-title] Cell cycle (Georgetown, Tex.)
  • [ISO-abbreviation] Cell Cycle
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, CD34; 0 / Neoplasm Proteins
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68. Kim HR, Shin JH, Lee JN, Lee EY: [Clinical significance of quantitation of WT1 gene expression for minimal residual disease monitoring of acute myelogenous leukemia]. Korean J Lab Med; 2007 Oct;27(5):305-12
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  • [Title] [Clinical significance of quantitation of WT1 gene expression for minimal residual disease monitoring of acute myelogenous leukemia].
  • BACKGROUND: Following induction chemotherapy for AML, a sensitive determination of minimal residual disease (MRD) in patients achieving complete remission (CR) should enable the detection of early relapse.
  • This study was designed to verify if quantitative assessment of the Wilms' tumor (WT1) gene by real time polymerase chain reaction (RQ-PCR) can be used as a marker for MRD detection during the monitoring of AML.
  • METHODS: WT1 gene expression was quantified by RQ-PCR in 31 patients with AML at diagnosis (27 patients) and during follow-up (29 patients) relative to ABL control gene.
  • Prognostic significance of WT1 gene expression was analyzed at diagnosis and at the primary CR evaluation.
  • Longitudinal WT1 gene analysis was performed in 17 AML patients.
  • RESULTS: At diagnosis, WT1 gene expression exceeded the control level in all of the patients.
  • Higher levels of WT1 gene expression were not associated with shorter event free survival or overall survival at diagnosis.
  • Relapse was observed in eight of 17 patients analysed longitudinally, and an increase of WT1 gene expression preceded morphologic relapse in four patients with the fusion transcript negative.
  • CONCLUSIONS: Quantitation of WT1 gene expression could be used for MRD monitoring of AML and for the early detection of relapse, especially in patients lacking specific molecular markers.
  • [MeSH-major] Genes, Wilms Tumor. Leukemia, Myelomonocytic, Acute / diagnosis. WT1 Proteins / analysis

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  • (PMID = 18094593.001).
  • [ISSN] 1598-6535
  • [Journal-full-title] The Korean journal of laboratory medicine
  • [ISO-abbreviation] Korean J Lab Med
  • [Language] kor
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Korea (South)
  • [Chemical-registry-number] 0 / Adaptor Proteins, Signal Transducing; 0 / PRAM1 protein, human; 0 / WT1 Proteins
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69. Kim HJ, Min WS, Eom KS, Cho BS, Kim SY, Bok JN, Kim KS, Min CK, Lee S, Cho SG, Kim DW, Lee JW, Kim CC: Anti-leukaemic role of acute GvHD after unrelated haematopoietic stem cell transplantation in intermediate- to high-risk acute myelogenous leukaemia. Bone Marrow Transplant; 2007 Dec;40(11):1069-74
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  • [Title] Anti-leukaemic role of acute GvHD after unrelated haematopoietic stem cell transplantation in intermediate- to high-risk acute myelogenous leukaemia.
  • Little is known about the role of acute GvHD (aGvHD) based on the concept of graft-versus-leukaemia effect (GVLE) after unrelated donor haematopoietic stem cell transplantation (uHSCT).
  • We evaluated 67 uHSCTs performed with multinational unrelated donors for patients with AML.
  • Specifically, high-risk AML patients had a much lower relapse rate when they developed aGvHD (P=0.01), compared with the intermediate-risk group.
  • Therefore, the development of aGvHD after uHSCT in AML patients is closely related to a lower relapse rate, probably in association with GVLE.
  • [MeSH-major] Graft vs Leukemia Effect. Hematopoietic Stem Cell Transplantation / methods. Leukemia, Myeloid, Acute / therapy. Neoplasm Recurrence, Local / prevention & control

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  • (PMID = 17922041.001).
  • [ISSN] 0268-3369
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Blood Group Antigens; 0 / HLA Antigens
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70. Ishaqi MK, Afzal S, Dupuis A, Doyle J, Gassas A: Outcome of allogeneic hematopoietic stem cell transplantation for children with acute myelogenous leukemia in second complete remission: single center experience. Pediatr Transplant; 2009 Dec;13(8):999-1003
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  • [Title] Outcome of allogeneic hematopoietic stem cell transplantation for children with acute myelogenous leukemia in second complete remission: single center experience.
  • We reviewed 26 consecutive patients with AML who were transplanted in second CR2 between 1994 and 2005.
  • Acute grade III-IV and chronic extensive GVHD occurred in eight (30%) and nine (35%) patients, respectively.
  • When entering remission, children with relapsed AML have a reasonable survival with HSCT, but relapse and TRM remain a concern.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation. Leukemia, Myeloid, Acute / therapy

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  • (PMID = 19032410.001).
  • [ISSN] 1399-3046
  • [Journal-full-title] Pediatric transplantation
  • [ISO-abbreviation] Pediatr Transplant
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Denmark
  • [Chemical-registry-number] 0 / Immunosuppressive Agents
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71. Valencia A, Román-Gómez J, Cervera J, Such E, Barragán E, Bolufer P, Moscardó F, Sanz GF, Sanz MA: Wnt signaling pathway is epigenetically regulated by methylation of Wnt antagonists in acute myeloid leukemia. Leukemia; 2009 Sep;23(9):1658-66
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  • [Title] Wnt signaling pathway is epigenetically regulated by methylation of Wnt antagonists in acute myeloid leukemia.
  • Activation of the Wnt signaling pathway has been implicated recently in the pathogenesis of leukemia.
  • We studied the function of epigenetic regulation of the Wnt pathway and its prognostic relevance in acute myelogenous leukemia (AML).
  • Aberrant methylation of Wnt antagonists was detected in four AML cell lines and in up to 64% of AML marrow samples.
  • In a subgroup of patients 60 years and younger with newly diagnosed AML and intermediate-risk cytogenetics, abnormal methylation of Wnt antagonists was associated with decreased 4-year relapse-free survival (28 vs 61%, respectively, P=0.03).
  • Our results indicate a function of the epigenetic regulation of the Wnt pathway in predicting relapse in a subgroup of AML patients.
  • [MeSH-major] DNA Methylation. Epigenesis, Genetic. Leukemia, Myeloid, Acute / genetics. Signal Transduction. Wnt Proteins / antagonists & inhibitors

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  • (PMID = 19387464.001).
  • [ISSN] 1476-5551
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Cell Cycle Proteins; 0 / DKK1 protein, human; 0 / Intercellular Signaling Peptides and Proteins; 0 / Membrane Proteins; 0 / SFRP2 protein, human; 0 / Wnt Proteins; 776B62CQ27 / decitabine; EC 2.7.11.1 / ATR protein, human; EC 2.7.11.1 / Ataxia Telangiectasia Mutated Proteins; EC 2.7.11.1 / Protein-Serine-Threonine Kinases; M801H13NRU / Azacitidine
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72. Huang TS, Myklebust LM, Kjarland E, Gjertsen BT, Pendino F, Bruserud Ø, Døskeland SO, Lillehaug JR: LEDGF/p75 has increased expression in blasts from chemotherapy-resistant human acute myelogenic leukemia patients and protects leukemia cells from apoptosis in vitro. Mol Cancer; 2007;6:31
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  • [Title] LEDGF/p75 has increased expression in blasts from chemotherapy-resistant human acute myelogenic leukemia patients and protects leukemia cells from apoptosis in vitro.
  • BACKGROUND: Relapse due to chemoresistant residual disease is a major cause of death in acute myelogenous leukemia (AML).
  • The present study was undertaken to elucidate the molecular mechanisms of chemoresistance by comparing differential gene expression in blasts from patients with resistant relapsing AML and chemosensitive AML.
  • RESULTS: About 20 genes were identified as preferentially expressed in blasts pooled from patients with resistant disease, as compared to chemosensitive AML blasts, based on differential gene expression screening.
  • Analysis of blasts from single patients disclosed that LEDGF/p75 was the most consistently upregulated mRNA in resistant AML.
  • Transfection experiments demonstrated that LEDGF/p75 and p52b antagonized daunorubicin-induced and cAMP-induced apoptosis in an AML cell line.
  • CONCLUSION: Our results provide evidence for an association between the overexpression of genes encoding survival proteins like LEDGF/p75 and chemo-resistance in acute myelogenous leukemia.
  • LEDGF/p75 has previously not been shown to protect against chemotherapy, and is a potential drug target in AML.
  • [MeSH-major] Apoptosis. Drug Resistance, Neoplasm / genetics. Gene Expression Regulation, Neoplastic. Intercellular Signaling Peptides and Proteins / metabolism. Leukemia, Myeloid, Acute / genetics. Leukemia, Myeloid, Acute / pathology. Lymphocyte Activation / genetics

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  • (PMID = 17451600.001).
  • [ISSN] 1476-4598
  • [Journal-full-title] Molecular cancer
  • [ISO-abbreviation] Mol. Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Intercellular Signaling Peptides and Proteins; 0 / Proto-Oncogene Proteins c-bcl-2; 0 / RNA, Messenger; 0 / lens epithelium-derived growth factor; E0399OZS9N / Cyclic AMP; ZS7284E0ZP / Daunorubicin
  • [Other-IDs] NLM/ PMC1876472
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73. Miller JS, Cooley S, Parham P, Farag SS, Verneris MR, McQueen KL, Guethlein LA, Trachtenberg EA, Haagenson M, Horowitz MM, Klein JP, Weisdorf DJ: Missing KIR ligands are associated with less relapse and increased graft-versus-host disease (GVHD) following unrelated donor allogeneic HCT. Blood; 2007 Jun 1;109(11):5058-61
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  • [Title] Missing KIR ligands are associated with less relapse and increased graft-versus-host disease (GVHD) following unrelated donor allogeneic HCT.
  • We analyzed data from 2062 patients undergoing unrelated donor HCT for acute myeloid leukemia (AML; n = 556), chronic myeloid leukemia (CML; n = 1224), and myelodysplastic syndrome (MDS; n = 282).
  • Missing 1 or more KIR ligands versus the presence of all ligands protected against relapse in patients with early myeloid leukemia (relative risk [RR] = 0.54; n = 536, 95% confidence interval [CI] 0.30-0.95, P = .03).
  • In the subset of CML patients that received a transplant beyond 1 year from diagnosis (n = 479), missing a KIR ligand independently predicted a greater risk of developing grade 3-4 acute graft-versus-host disease (GVHD; RR = 1.58, 95% CI 1.13-2.22; P = .008).
  • These data support a genetically determined role for NK cells following unrelated HCT in myeloid leukemia.

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  • (PMID = 17317850.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / P01 CA111412; United States / NCI NIH HHS / CA / P01 CA 111412
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Ligands; 0 / Receptors, Immunologic; 0 / Receptors, KIR
  • [Other-IDs] NLM/ PMC1885526
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74. Sanz J, Sanz MA, Saavedra S, Lorenzo I, Montesinos P, Senent L, Planelles D, Larrea L, Martín G, Palau J, Jarque I, Martínez J, de la Rubia J, Moscardó F, Romero M, Luna I, Montava A, Cañabate S, Sanz GF: Cord blood transplantation from unrelated donors in adults with high-risk acute myeloid leukemia. Biol Blood Marrow Transplant; 2010 Jan;16(1):86-94
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  • [Title] Cord blood transplantation from unrelated donors in adults with high-risk acute myeloid leukemia.
  • We analyzed the outcome and prognostic factors of 49 adults with high-risk acute myelogenous leukemia (AML) receiving single-unit CBT from unrelated donors after myeloablative (MA) conditioning at a single institution.
  • Confidence Interval of graft-versus-host disease (GVHD), acute GVHD (aGVHD) grade II-IV, III-IV, and extensive chronic GVHD (cGVHD) were 26%, 15%, and 30%, respectively.
  • Leukemia-free survival (LFS), nonrelapse mortality (NRM), and relapse at 2 years were 42%, 39%, and 19%, respectively.
  • These results show that CBT from unrelated donors is a curative treatment for a substantial number of patients with high-risk AML, particularly if transplant is performed with highly cellular units in patients in first CR.
  • [MeSH-major] Cord Blood Stem Cell Transplantation. Leukemia, Myeloid, Acute / therapy

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  • [Copyright] Copyright (c) 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
  • (PMID = 19744570.001).
  • [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
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, CD34
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75. Latagliata R, Breccia M, Fazi P, Iacobelli S, Martinelli G, Di Raimondo F, Sborgia M, Fabbiano F, Pirrotta MT, Zaccaria A, Amadori S, Caramatti C, Falzetti F, Candoni A, Mattei D, Morselli M, Alimena G, Vignetti M, Baccarani M, Mandelli F: Liposomal daunorubicin versus standard daunorubicin: long term follow-up of the GIMEMA GSI 103 AMLE randomized trial in patients older than 60 years with acute myelogenous leukaemia. Br J Haematol; 2008 Dec;143(5):681-9
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  • [Title] Liposomal daunorubicin versus standard daunorubicin: long term follow-up of the GIMEMA GSI 103 AMLE randomized trial in patients older than 60 years with acute myelogenous leukaemia.
  • This randomized phase III clinical trial explored the efficacy of DaunoXome (DNX) versus Daunorubicin (DNR) in acute myeloid leukaemia (AML) patients aged >60 years.
  • Three hundred and one AML patients were randomized to receive DNR (45 mg/m(2) days 1-3) or DNX (80 mg/m(2) days 1-3) plus cytarabine (AraC; 100 mg/m(2) days 1-7).
  • After CR, DNX showed a higher incidence of early deaths (12.5% vs. 2.6% at 6 months, P = 0.053) but a lower incidence of relapse beyond 6 months (59% vs. 78% at 24 months, P = 0.064), with a cross in overall survival (OS) and disease-free survival (DFS) curves and a later advantage for DNX arm after 12 months from diagnosis.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Daunorubicin / administration & dosage. Leukemia, Myeloid, Acute / drug therapy

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  • (PMID = 18950458.001).
  • [ISSN] 1365-2141
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase III; Journal Article; Randomized Controlled Trial
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Liposomes; ZS7284E0ZP / Daunorubicin
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76. Kornblau SM, Singh N, Qiu Y, Chen W, Zhang N, Coombes KR: Highly phosphorylated FOXO3A is an adverse prognostic factor in acute myeloid leukemia. Clin Cancer Res; 2010 Mar 15;16(6):1865-74
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  • [Title] Highly phosphorylated FOXO3A is an adverse prognostic factor in acute myeloid leukemia.
  • PURPOSE: The Forkhead transcription factors (FOXO) are tumor suppressor genes regulating differentiation, metabolism, and apoptosis that functionally interact with signal transduction pathways shown to be deregulated and prognostic in acute myelogenous leukemia (AML).
  • This study evaluated the level of expression and the prognostic relevance of total and phosphorylated FOXO3A protein in AML.
  • EXPERIMENTAL DESIGN: We used reverse-phase protein array methods to measure the level of total and phosphoprotein expression of FOXO3A, in leukemia-enriched protein samples from 511 newly diagnosed AML patients.
  • Levels of total FOXO3A were higher at relapse compared with diagnosis.
  • CONCLUSIONS: High levels of phosphorylation of FOXO3A is a therapeutically targetable, independent adverse prognostic factor in AML.
  • [MeSH-major] Forkhead Transcription Factors / metabolism. Leukemia, Myeloid, Acute / metabolism. Leukemia, Promyelocytic, Acute / metabolism. Neoplasm Proteins / metabolism

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  • (PMID = 20215543.001).
  • [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 / P01 CA108631
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, CD34; 0 / FOXO3 protein, human; 0 / Forkhead Transcription Factors; 0 / Neoplasm Proteins
  • [Other-IDs] NLM/ NIHMS378348; NLM/ PMC3385949
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77. Callera F, Mulin CC, Rosa ES, Melo DB, Melo CM: High prevalence of morphological subtype FAB M1 in adults with de novo acute myeloid leukemia in São José dos Campos, São Paulo. Sao Paulo Med J; 2006 Jan 5;124(1):45-7
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  • [Title] High prevalence of morphological subtype FAB M1 in adults with de novo acute myeloid leukemia in São José dos Campos, São Paulo.
  • CONTEXT AND OBJECTIVE: Geographical variations have been described in acute myelogenous leukemia (AML).
  • The aim of this study was to demonstrate the high prevalence of French-American-British (FAB) M1 subtype in adults with de novo AML in São José dos Campos, State of São Paulo, Brazil.
  • METHODS: Records from 39 consecutive adult patients with de novo AML referred to Hospital Pio XII between January 2002 and September 2004 were reviewed.
  • The rates of remission, relapse, mortality according treatment phase, survival and leukemia-free survival were calculated.
  • The remission and the relapse rates were 82% and 41% respectively.
  • The mortality rate was 69% (induction of remission: 7/39, 17.9%; post induction: 10/32, 31.2%; and relapse: 10/16, 62.5%).
  • The survival rate was 30% and leukemia-free survival was 33%.
  • CONCLUSIONS: The study demonstrated a high prevalence of FAB M1 subtype in adults with de novo AML in São José dos Campos.
  • Our data suggest the occurrence of different regional prevalences of FAB AML categories in Brazil.
  • [MeSH-major] Leukemia, Myeloid, Acute / pathology

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  • (PMID = 16612463.001).
  • [ISSN] 1516-3180
  • [Journal-full-title] São Paulo medical journal = Revista paulista de medicina
  • [ISO-abbreviation] Sao Paulo Med J
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Brazil
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78. Al-Ali H, Cross M, Lange T, Freund M, Dölken G, Niederwieser D: Low-dose total body irradiation-based regimens as a preparative regimen for allogeneic haematopoietic cell transplantation in acute myelogenous leukaemia. Curr Opin Oncol; 2009 Jun;21 Suppl 1:S17-22
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  • [Title] Low-dose total body irradiation-based regimens as a preparative regimen for allogeneic haematopoietic cell transplantation in acute myelogenous leukaemia.
  • Although much progress has been made in understanding the molecular basis of acute myeloid leukaemia (AML), this has not yet led to major improvements in the overall survival of patients.
  • In particular, the treatment of elderly patients with AML remains one of the major challenges in haematology.
  • Despite increases in complete remission rates, relapse remains a major obstacle and the major determinant of overall survival.
  • Allogeneic stem cell transplantation (SCT) is the most efficient antileukaemic treatment for patients with AML, but eligibility for the treatment was confined for a long time to younger patients.
  • TRM does not currently exceed 10-12% in related and 20% in unrelated SCT even in patients up to the age of 75 years, so that relapse after transplantation remains the major problem.
  • A number of strategies for decreasing relapse rates has been developed.
  • This has led to decreases in the relapse rate over the past few years.
  • Randomized studies are now being initiated to define the role of SCT in the treatment of elderly patients with AML.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation. Leukemia, Myeloid, Acute / radiotherapy. Transplantation Conditioning / methods. Whole-Body Irradiation / methods
  • [MeSH-minor] Aged. Aged, 80 and over. Chimerism. Combined Modality Therapy. Graft Rejection. Graft vs Leukemia Effect. Humans. Transplantation, Homologous. Treatment Outcome

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  • (PMID = 19561407.001).
  • [ISSN] 1531-703X
  • [Journal-full-title] Current opinion in oncology
  • [ISO-abbreviation] Curr Opin Oncol
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
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79. Lee SE, Kim HJ, Min WS, Cho BS, Eom KS, Kim YJ, Min CK, Lee S, Cho SG, Kim DW, Lee JW, Park CW, Kim CC: Favorable outcomes of intravenous busulfan, fludarabine, and 400 cGy total body irradiation-based reduced-intensity conditioning allogeneic stem cell transplantation for acute myelogenous leukemia with old age and/or co-morbidities. Int J Hematol; 2010 Sep;92(2):342-50
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  • [Title] Favorable outcomes of intravenous busulfan, fludarabine, and 400 cGy total body irradiation-based reduced-intensity conditioning allogeneic stem cell transplantation for acute myelogenous leukemia with old age and/or co-morbidities.
  • To define the role of RIC in AML with old age (>or=55 years) and/or co-morbidities (HCT-CI scores >or=2), we analyzed patients who received allogeneic stem cell transplantation (SCT) with Flu/Bu/TBI 400 cGy/+/-antithymocyte globulin (ATG) conditioning regimen.
  • At a median follow-up of 18 months (range 4-40) for survivors, the estimated 2-year rates of overall survival, event-free survival, transplantation-related mortality, and relapse were 66, 63, 26, and 16%, respectively.
  • The incidence of acute (grades II-IV) and chronic GVHD by NIH consensus criteria was 34.4 and 62.5%.
  • This study suggests that the Flu/Bu/TBI 400 cGy or Flu/Bu/TBI 400 cGy/ATG-based conditioning regimens maybe a feasible therapeutic approach for AML with old age and/or co-morbidities.
  • [MeSH-minor] Age Factors. Aged. Aged, 80 and over. Antineoplastic Agents. Antineoplastic Agents, Alkylating. Comorbidity. Female. Humans. Leukemia, Myeloid, Acute. Male. Middle Aged. Survival Analysis. Transplantation Conditioning / methods. Transplantation, Homologous. Treatment Outcome

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  • (PMID = 20694843.001).
  • [ISSN] 1865-3774
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Antineoplastic Agents, Alkylating; FA2DM6879K / Vidarabine; G1LN9045DK / Busulfan; P2K93U8740 / fludarabine
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80. Buccisano F, Maurillo L, Gattei V, Del Poeta G, Del Principe MI, Cox MC, Panetta P, Consalvo MI, Mazzone C, Neri B, Ottaviani L, Fraboni D, Tamburini A, Lo-Coco F, Amadori S, Venditti A: The kinetics of reduction of minimal residual disease impacts on duration of response and survival of patients with acute myeloid leukemia. Leukemia; 2006 Oct;20(10):1783-9
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  • [Title] The kinetics of reduction of minimal residual disease impacts on duration of response and survival of patients with acute myeloid leukemia.
  • We assessed by multiparametric flow cytometry the levels of minimal residual disease (MRD) in 100 adult patients with acute myelogenous leukemia (AML) achieving complete remission after intensive chemotherapy.
  • Post-Cons MRD- patients had a superior outcome in terms of relapse rate, overall survival (OS) and relapse-free survival (RFS) (P<0.001, for all comparisons), regardless of the MRD status after induction.
  • Multivariate analysis, including karyotype, age, MDR1 phenotype, post-Ind and post-Cons MRD levels, indicated that the post-Cons MRD status independently affected relapse rate, OS and RFS (P<0.001, for all comparisons).
  • (1) the threshold of 3.5 x 10(-4) is valid in discriminating risk categories in adult AML and (2) post-Cons MRD assessment is critical to predict disease outcome.
  • [MeSH-major] Leukemia, Myeloid, Acute / mortality. Leukemia, Myeloid, Acute / pathology. Neoplasm, Residual / mortality. Neoplasm, Residual / pathology

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  • (PMID = 16838027.001).
  • [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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81. Huang XJ, Liu DH, Liu KY, Xu LP, Chen H, Han W, Chen YH, Zhang XH, Lu DP: Treatment of acute leukemia with unmanipulated HLA-mismatched/haploidentical blood and bone marrow transplantation. Biol Blood Marrow Transplant; 2009 Feb;15(2):257-65
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  • [Title] Treatment of acute leukemia with unmanipulated HLA-mismatched/haploidentical blood and bone marrow transplantation.
  • Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains one of the best therapeutic options to cure acute leukemia (AL).
  • The incidence of grade 2-4 acute graft-versus-host disease (aGVHD) was 45.8%, and that of grades 3 and 4 was 13.4%, which was not associated with the extent of HLA disparity.
  • Seventeen patients received DLI as a treatment for relapse after transplantation and 7 patients achieved leukemia-free survival (LFS).
  • The 3-year probability of LFS for acute myelogenous leukemia (AML) was 70.7% and 55.9%, and for acute lymphoblastic leukemia (ALL) it was 59.7% and 24.8% in standard-risk and high-risk groups, respectively.
  • Lower LFS were associated with diagnosis of acute leukemia in the high-risk group (P= .001, relative risk [RR], 95% confidence interval [CI]: 2.94[1.535-5.631]) and the occurrence of aGVHD of grades 3 and 4 (P= .004).
  • [MeSH-major] Bone Marrow Transplantation / methods. HLA Antigens / immunology. Haplotypes / immunology. Histocompatibility / immunology. Leukemia / therapy. Peripheral Blood Stem Cell Transplantation / methods
  • [MeSH-minor] Acute Disease. Adolescent. Adult. Child. Child, Preschool. Disease-Free Survival. Female. Graft vs Host Disease / immunology. HLA-A Antigens. HLA-B Antigens. HLA-DR Antigens. Humans. Leukemia, Myeloid, Acute / mortality. Leukemia, Myeloid, Acute / therapy. Male. Middle Aged. Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy. Transplantation, Homologous / immunology. Treatment Outcome. Young Adult

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  • (PMID = 19167686.001).
  • [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
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / HLA Antigens; 0 / HLA-A Antigens; 0 / HLA-B Antigens; 0 / HLA-DR Antigens
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82. Kröger N, Brand R, van Biezen A, Cahn JY, Slavin S, Blaise D, Sierra J, Zander A, Niederwieser D, de Witte T, Myelodysplastic Syndromes Subcommittee of The Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT): Autologous stem cell transplantation for therapy-related acute myeloid leukemia and myelodysplastic syndrome. Bone Marrow Transplant; 2006 Jan;37(2):183-9
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  • [Title] Autologous stem cell transplantation for therapy-related acute myeloid leukemia and myelodysplastic syndrome.
  • We report the results of 65 patients with treatment-related myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) who were transplanted from an autograft and reported to the EBMT.
  • The primary disease was solid tumors (n = 37), Hodgkin's disease (n = 13), non-Hodgkin's lymphoma (n = 10), acute lymphoblastic leukemia (n = 2) or myeloproliferative syndromes (n = 3).
  • The types of MDS were as follows: RAEB (n = 1; 2%), RAEB-t (n = 3; 5%), or AML (n = 56; 87%).
  • The median time between diagnosis and transplantation was 5 months (range, 3-86).
  • The cumulative incidence of relapse was 58% (95% CI: 44-72%) and of treatment-related mortality 12% (95% CI: 6-38%).
  • Lower relapse rate was seen in patients transplanted in first complete remission (CR1 vs non-CR1: 3 years: 48 vs 89%; P = 0.05).
  • Autologous transplantation may cure a substantial number of patients with treatment-related MDS/AML, especially if they are in CR1 and of younger age.
  • [MeSH-major] Leukemia, Myeloid, Acute / mortality. Leukemia, Myeloid, Acute / therapy. Myelodysplastic Syndromes / mortality. Myelodysplastic Syndromes / therapy. Neoplasms, Second Primary / mortality. Neoplasms, Second Primary / therapy. Stem Cell Transplantation


83. Davies SM, Wang D, Wang T, Arora M, Ringden O, Anasetti C, Pavletic S, Casper J, Macmillan ML, Sanders J, Wall D, Kernan NA: Recent decrease in acute graft-versus-host disease in children with leukemia receiving unrelated donor bone marrow transplants. Biol Blood Marrow Transplant; 2009 Mar;15(3):360-6
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  • [Title] Recent decrease in acute graft-versus-host disease in children with leukemia receiving unrelated donor bone marrow transplants.
  • Unrelated donor (URD) bone marrow transplantation (BMT) is an effective treatment for leukemia in children, but its success is threatened by graft-versus-host disease (GVHD) and relapse.
  • We analyzed outcomes of 638 myeloablative URD BMTs performed between 1990 and 2003 to treat acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia, or myelodysplastic syndrome MDS, using the Center for International Blood and Marrow Transplant Research (CIBMTR) database.
  • Overall, 27% of the recipients developed acute GVHD (aGVHD) grade III-IV; the risk was significantly higher in children receiving T cell-replete grafts compared with those receiving T cell-depleted grafts (odds ratio [OR] = 3.12; 95% confidence interval [CI] = 2.02 to 4.83; P < .0001).
  • Acute GVHD significantly reduced the risk of relapse in children with ALL (OR = 0.34; 95% CI = 0.13 to 0.86; P = .0052), but not in those with AML (OR = 0.58; 95% CI = 0.22 to 2.98; P = .26).
  • [MeSH-minor] Adolescent. Child. Child, Preschool. Disease-Free Survival. Female. Hematopoietic Stem Cell Transplantation / adverse effects. Humans. Leukemia / immunology. Male. Multivariate Analysis. Recurrence. Retrospective Studies. Risk Factors. Tissue Donors. Treatment Outcome

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  • (PMID = 19203727.001).
  • [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 / U24 CA076518
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Other-IDs] NLM/ NIHMS219377; NLM/ PMC3365559
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84. McClune BL, Weisdorf DJ, Pedersen TL, Tunes da Silva G, Tallman MS, Sierra J, Dipersio J, Keating A, Gale RP, George B, Gupta V, Hahn T, Isola L, Jagasia M, Lazarus H, Marks D, Maziarz R, Waller EK, Bredeson C, Giralt S: Effect of age on outcome of reduced-intensity hematopoietic cell transplantation for older patients with acute myeloid leukemia in first complete remission or with myelodysplastic syndrome. J Clin Oncol; 2010 Apr 10;28(11):1878-87
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  • [Title] Effect of age on outcome of reduced-intensity hematopoietic cell transplantation for older patients with acute myeloid leukemia in first complete remission or with myelodysplastic syndrome.
  • PURPOSE Acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) primarily afflict older individuals.
  • To define prognostic factors impacting long-term outcomes of RIC regimens in patients older than age 40 years with AML in first complete remission or MDS and to determine the impact of age, we analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR).
  • Outcomes analyzed included neutrophil recovery, incidence of acute or chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), relapse, disease-free survival (DFS), and overall survival (OS).
  • RESULTS Univariate analyses demonstrated no age group differences in NRM, grade 2 to 4 acute GVHD, chronic GVHD, or relapse.
  • Patients age 40 to 54, 55 to 59, 60 to 64, and > or = 65 years had 2-year survival rates as follows: 44% (95% CI, 37% to 52%), 50% (95% CI, 41% to 59%), 34% (95% CI, 25% to 43%), and 36% (95% CI, 24% to 49%), respectively, for patients with AML (P = .06); and 42% (95% CI, 35% to 49%), 35% (95% CI, 27% to 43%), 45% (95% CI, 36% to 54%), and 38% (95% CI, 25% to 51%), respectively, for patients with MDS (P = .37).
  • Multivariate analysis revealed no significant impact of age on NRM, relapse, DFS, or OS (all P > .3).
  • Unfavorable cytogenetics adversely impacted relapse, DFS, and OS.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation. Leukemia, Myeloid, Acute / therapy. Neoplasm Recurrence, Local / therapy


85. Bierings M, Nachman JB, Zwaan CM: Stem cell transplantation in pediatric leukemia and myelodysplasia: state of the art and current challenges. Curr Stem Cell Res Ther; 2007 Jan;2(1):53-63
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  • [Title] Stem cell transplantation in pediatric leukemia and myelodysplasia: state of the art and current challenges.
  • The role of stem cell transplantation in the treatment of leukemia and myelodysplasia (MDS) in children has changed over the past decade.
  • In pediatric acute lymphoblastic leukemia (ALL), the overall cure-rate is high with conventional chemotherapy.
  • However, selected patients with a high-risk of relapse are often treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first remission (CR1).
  • Patients with a bone-marrow relapse who attain a second remission frequently receive HSCT.
  • High minimal residual disease (MRD) levels directly prior to HSCT determines the relapse risk.
  • In pediatric acute myeloid leukemia (AML) the role of allo-HSCT in CR1 is declining, due to better outcome with modern multi-agent chemotherapy.
  • In relapsed AML patients, allo-HSCT still seems indispensable.
  • Targeted therapy may change the role of HSCT, in particular in chronic myeloid leukemia, where the role of allografting is changing in the imatinib era.
  • [MeSH-major] Leukemia / therapy. Myelodysplastic Syndromes / therapy. Stem Cell Transplantation / trends
  • [MeSH-minor] Child. Humans. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy. Leukemia, Myeloid, Acute / therapy


86. Heuser M, Beutel G, Krauter J, Döhner K, von Neuhoff N, Schlegelberger B, Ganser A: High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics. Blood; 2006 Dec 1;108(12):3898-905
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  • [Title] High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics.
  • The translocation t(12;22) involves MN1 and TEL and is rarely found in acute myeloid leukemia (AML).
  • Recently, it has been shown in a mouse model that the fusion protein MN1-TEL can promote growth of primitive hematopoietic progenitor cells (HPCs) and, in cooperation with HOXA9, induce AML.
  • We quantified MN1 expression by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in 142 adult patients with AML with normal cytogenetics treated uniformly in trial AML-SHG 01/99.
  • AML samples were dichotomized at the median MN1 expression.
  • High MN1 expression was significantly correlated with unmutated NPM1 (P < .001), poor response to the first course of induction treatment (P = .02), a higher relapse rate (P = .03), and shorter relapse-free (P = .002) and overall survivals (P = .03).
  • Excluding patients with NPM1(mutated)/FLT3ITD(negative), high MN1 expression was associated with shorter relapse-free survival (P = .057).
  • MN1 was highly expressed in some patients with acute lymphoblastic but not chronic lymphocytic or myeloid leukemia.
  • In conclusion, our data suggest MN1 overexpression as a new prognostic marker in AML with normal cytogenetics.
  • [MeSH-major] Biomarkers, Tumor / biosynthesis. Gene Expression Regulation, Leukemic. Leukemia, Myeloid, Acute / metabolism. Tumor Suppressor Proteins / biosynthesis
  • [MeSH-minor] Adolescent. Adult. Animals. Cytogenetic Analysis / methods. Disease-Free Survival. Female. Homeodomain Proteins / genetics. Homeodomain Proteins / metabolism. Humans. Leukemia, Lymphocytic, Chronic, B-Cell / genetics. Leukemia, Lymphocytic, Chronic, B-Cell / metabolism. Leukemia, Lymphocytic, Chronic, B-Cell / mortality. Leukemia, Lymphocytic, Chronic, B-Cell / therapy. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / mortality. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy. Male. Mice. Middle Aged. Oncogene Proteins, Fusion / biosynthesis. Oncogene Proteins, Fusion / genetics. Predictive Value of Tests. Reverse Transcriptase Polymerase Chain Reaction. Survival Rate. Transcription Factors / biosynthesis. Transcription Factors / genetics

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  • (PMID = 16912223.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Clinical Trial; Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Homeodomain Proteins; 0 / MN1 protein, human; 0 / MN1-TEL fusion protein, human; 0 / Oncogene Proteins, Fusion; 0 / Transcription Factors; 0 / Tumor Suppressor Proteins; 0 / homeobox protein HOXA9
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87. Godder KT, Henslee-Downey PJ, Mehta J, Park BS, Chiang KY, Abhyankar S, Lamb LS: Long term disease-free survival in acute leukemia patients recovering with increased gammadelta T cells after partially mismatched related donor bone marrow transplantation. Bone Marrow Transplant; 2007 Jun;39(12):751-7
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  • [Title] Long term disease-free survival in acute leukemia patients recovering with increased gammadelta T cells after partially mismatched related donor bone marrow transplantation.
  • Allogeneic stem cell transplantation (ASCT) has improved leukemia-free survival (LFS) in many but not all patients with acute leukemia.
  • This is an eight-year follow-up to our previous study showing a survival advantage to patients with an increased gammadelta T cells following ASCT. gammadelta T cell levels were collected prospectively in 153 patients (acute lymphoblastic leukemia (ALL) n = 77; acute myelogenous leukemia (AML) n = 76) undergoing partially mismatched related donor ASCT.
  • Median age was 22 years (1-59), and 62% of the patients were in relapse at transplant.
  • In conclusion, gammadelta T cells may facilitate a graft-versus-leukemia (GvL) effect, without causing GvHD.
  • Further evaluations of this effect may lead to specific immunotherapy for patients with refractory leukemia.
  • [MeSH-major] Bone Marrow Transplantation. Histocompatibility Testing. Leukemia, Myeloid, Acute / therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy. Receptors, Antigen, T-Cell, gamma-delta / metabolism

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  • (PMID = 17450185.001).
  • [ISSN] 0268-3369
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / R21 CA 76667
  • [Publication-type] Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Receptors, Antigen, T-Cell, gamma-delta
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88. Gu WY, Chen ZX, Hu SY, Zhu J, Wang ZL, Yan F, Wang W, Cen JN, Shen HL, Qian J: [Significance of dynamic detection of WT1 expression on monitoring minimal residual disease in leukemia patients following allogeneic bone marrow transplantation]. Zhonghua Yi Xue Za Zhi; 2005 Feb 23;85(7):444-7
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  • [Title] [Significance of dynamic detection of WT1 expression on monitoring minimal residual disease in leukemia patients following allogeneic bone marrow transplantation].
  • OBJECTIVE: To investigate the significance of monitoring Wilms' tumor gene (WT1) expression level in bone marrow of leukemia patients following allogeneic bone marrow transplantation (allo-BMT).
  • METHODS: Real-time quantitative reverse transcription polymerase chain reaction method was established for measuring WT1 and GAPDH expression levels in bone marrow cells of 15 patients with leukemia, including a total of 111 specimens during the follow-up, and in 23 non-leukemia patients by using LightCycler.
  • RESULTS: The median expression levels of WT1(N) in 17 samples of newly diagnosed patients, 6 samples of relapsed patients, 88 samples from leukemia patient in complete remission and 23 samples of non-leukemic controls were 40.18 (5.48 to 510.27), 125.89 (34.50 to 273.95), 4.80 (0 to 56.96) and 1.47 (0 to 8.56) respectively.
  • Spearman Rho correlation analysis revealed that the correlation coefficient between the WT1(N) expression levels and BCR/ABL, AML/ETO, PML/RARalpha and MLL/AF17 fusion genes expression were 0.678 (P = 0.00), 0.677 (P = 0.00), 0.806 (P = 0.00) and 0.553 (P = 0.049) respectively.
  • A re-increment of WT1(N) expression level during follow-up could be detected 40 to 180 days earlier to hematological relapse.
  • CONCLUSION: The WT1 expression level of leukemia patients following allo-BMT measured by real time RT-PCR can be a useful tool for monitoring MRD and warning the clinical relapse during follow-up.
  • [MeSH-major] Bone Marrow Transplantation. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism. Leukemia, Myeloid, Acute / metabolism. WT1 Proteins / biosynthesis


89. Hassane DC, Guzman ML, Corbett C, Li X, Abboud R, Young F, Liesveld JL, Carroll M, Jordan CT: Discovery of agents that eradicate leukemia stem cells using an in silico screen of public gene expression data. Blood; 2008 Jun 15;111(12):5654-62
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Discovery of agents that eradicate leukemia stem cells using an in silico screen of public gene expression data.
  • Increasing evidence indicates that malignant stem cells are important for the pathogenesis of acute myelogenous leukemia (AML) and represent a reservoir of cells that drive the development of AML and relapse.
  • Therefore, new treatment regimens are necessary to prevent relapse and improve therapeutic outcomes.
  • Previous studies have shown that the sesquiterpene lactone, parthenolide (PTL), ablates bulk, progenitor, and stem AML cells while causing no appreciable toxicity to normal hematopoietic cells.
  • Thus, PTL must evoke cellular responses capable of mediating AML selective cell death.
  • Given recent advances in chemical genomics such as gene expression-based high-throughput screening (GE-HTS) and the Connectivity Map, we hypothesized that the gene expression signature resulting from treatment of primary AML with PTL could be used to search for similar signatures in publicly available gene expression profiles deposited into the Gene Expression Omnibus (GEO).
  • We therefore devised a broad in silico screen of the GEO database using the PTL gene expression signature as a template and discovered 2 new agents, celastrol and 4-hydroxy-2-nonenal, that effectively eradicate AML at the bulk, progenitor, and stem cell level.
  • These findings suggest the use of multicenter collections of high-throughput data to facilitate discovery of leukemia drugs and drug targets.

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  • (PMID = 18305216.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R01 CA090446; United States / NCI NIH HHS / CA / T32 CA009363; United States / NCI NIH HHS / CA / 5T32-CA09363; United States / NCI NIH HHS / CA / R01CA90446
  • [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 / Aldehydes; 0 / Anti-Inflammatory Agents, Non-Steroidal; 0 / Antineoplastic Agents; 0 / Cysteine Proteinase Inhibitors; 0 / Sesquiterpenes; 0 / Terpenes; 0 / Triterpenes; 29343-52-0 / 4-hydroxy-2-nonenal; 2RDB26I5ZB / parthenolide; 34157-83-0 / tripterine
  • [Other-IDs] NLM/ PMC2424160
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90. Guzman ML, Li X, Corbett CA, Rossi RM, Bushnell T, Liesveld JL, Hébert J, Young F, Jordan CT: Rapid and selective death of leukemia stem and progenitor cells induced by the compound 4-benzyl, 2-methyl, 1,2,4-thiadiazolidine, 3,5 dione (TDZD-8). Blood; 2007 Dec 15;110(13):4436-44
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  • [Title] Rapid and selective death of leukemia stem and progenitor cells induced by the compound 4-benzyl, 2-methyl, 1,2,4-thiadiazolidine, 3,5 dione (TDZD-8).
  • Leukemia is thought to arise from malignant stem cells, which have been described for acute and chronic myeloid leukemia (AML and CML) and for acute lymphoblastic leukemia (ALL).
  • Leukemia stem cells (LSCs) are relatively resistant to current chemotherapy and likely contribute to disease relapse and progression.
  • Analysis of primary AML, blast crisis CML (bcCML), ALL, and chronic lymphoblastic leukemia (CLL) specimens showed rapid induction of cell death upon treatment with TDZD-8.
  • We conclude that TDZD-8 uses a unique and previously unknown mechanism to rapidly target leukemia cells, including malignant stem and progenitor populations.

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  • (PMID = 17785584.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R01 CA090446; United States / NCI NIH HHS / CA / R01 CA90446
  • [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 / 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione; 0 / Sulfhydryl Compounds; 0 / Thiadiazoles; EC 2.7.10.1 / FLT3 protein, human; EC 2.7.10.1 / fms-Like Tyrosine Kinase 3; EC 2.7.11.13 / Protein Kinase C
  • [Other-IDs] NLM/ PMC2234782
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91. 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.
  • The low induction rate of GVHD and extramedullary relapse after remission is achieved with DLI are problems yet to be solved.
  • [MeSH-major] Antimetabolites, Antineoplastic / administration & dosage. Cytarabine / administration & dosage. Graft vs Host Disease / therapy. Leukemia / therapy. Lymphocyte Transfusion. Peripheral Blood Stem Cell Transplantation

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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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92. Al-Tonbary Y, Mansour AK, Ghazy H, Elghannam DM, Abd-Elghaffar HA: Prognostic significance of foetal-like tyrosine kinase 3 mutation in Egyptian children with acute leukaemia. Int J Lab Hematol; 2009 Jun;31(3):320-6
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  • [Title] Prognostic significance of foetal-like tyrosine kinase 3 mutation in Egyptian children with acute leukaemia.
  • In children with acute myelogenous leukaemia (AML), internal tandem duplication of the Flt3 gene (Flt3/ITD) was previously reported and correlated to poor prognosis.
  • Limited data are available about childhood acute lymphoblastic leukaemia (ALL).
  • We analysed bone marrow specimens from 55 newly diagnosed acute leukaemia cases including 30 AML and 25 ALL by genomic PCR for the presence of Flt3/ITD and correlated its presence with clinical outcome.
  • Tandem duplication was found in 6/30(20%) AML cases: 2/8 M1, 1/8 M2, 2/6 M3, 1/6 M4 with loss of heterozygosity (LOH) in two cases.
  • Patients with Flt3/ITD appear to be refractory to primary induction therapy, and for those who achieve remission, there is a high rate of relapse and death so there may be an association between this type of mutation and patient outcome.
  • [MeSH-major] Leukemia, Myeloid, Acute / therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy. fms-Like Tyrosine Kinase 3 / genetics

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  • (PMID = 18336585.001).
  • [ISSN] 1751-553X
  • [Journal-full-title] International journal of laboratory hematology
  • [ISO-abbreviation] Int J Lab Hematol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] EC 2.7.10.1 / FLT3 protein, human; EC 2.7.10.1 / fms-Like Tyrosine Kinase 3
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93. Alimoghaddam K, Ghaffari H, Foroughi F, Chardouli B, Sanaat Z, Bahar B, Mousavi A, Iravani M, Ghavamzadeh A: Effects of chimerism on graft-versus-host disease, disease recurrence, and survival after HLA-identical marrow transplantation in Iran. Arch Iran Med; 2006 Apr;9(2):99-103
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  • METHODS: The association of MC with acute GVHD, disease recurrence, survival, and relapse-free survival was investigated in 91 patients who underwent either bone (n = 12) or peripheral blood (n = 79) HLA-identical marrow transplantation.
  • Patients had thalassemia (n = 19), acute myelogenous leukemia (AML) (n = 29), acute lymphocytic leukemia (ALL) (n = 20), chronic myelogenous leukemia (CML) (n = 18), and other diseases (n = 5).
  • The incidence of acute GVHD was significantly (P = 0.01) lower in mixed chimeras than in complete chimeras.
  • There was no significant difference in acute GVHD grade (I, II vs. III, IV) between the two groups.
  • The incidence of relapse was 18%.
  • There was no difference in relapse rate between MC and CC groups.
  • Relapse-free survival was 80% that was not significantly different between the two groups.
  • CONCLUSION: Despite some previous reports, we found no significant difference in the survival and relapse rates between MC and CC groups.
  • [MeSH-minor] Adolescent. Adult. Child. Child, Preschool. Female. Graft Rejection / epidemiology. Humans. Iran. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / mortality. Leukemia, Myeloid, Acute / immunology. Leukemia, Myeloid, Acute / mortality. Male. Middle Aged. Minisatellite Repeats. Polymerase Chain Reaction. Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology. Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality. Recurrence. Survival Analysis. Thalassemia / immunology. Thalassemia / mortality. Transplantation Conditioning. Transplantation, Homologous

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  • (PMID = 16649348.001).
  • [ISSN] 1029-2977
  • [Journal-full-title] Archives of Iranian medicine
  • [ISO-abbreviation] Arch Iran Med
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Iran
  • [Chemical-registry-number] 0 / HLA Antigens
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94. Sharma S, Pati HP: Erythrocyte enzyme abnormalities in leukemias. J Assoc Physicians India; 2006 Jun;54:453-7
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Red cell enzymes were assayed in a total of 67 patient including 24 patients with AML (19 relapse, 5 remission), 16 patients with ALL (10 relapse, 6 remission), 22 patients with CML and 5 patients with blastic CML.
  • Diagnosis of leukemia was based on clinical presentation, peripheral blood smear and bone marrow examination (as per FAB classification).
  • Red cell HK was high in all leukemia subtypes.
  • Notably there was no PK deficiency in AML or G6PD deficiency in ALL.
  • Activities of G6PD and PK could be correlated in cases of CML, AML, (p<0.05) and ALL (p<0.01) i.e. when there was increased activity of G6PD, PK activity also tended to be higher.
  • HK activity showed a positive correlation with PK and G6PD activity in cases of CML (p<0.05), however in acute leukemia there was no such correlation.
  • Alteration of enzyme activities among red cells in leukemia occurred only during relapse.
  • It would therefore, appear that enzyme alterations seen in leukemia patients is due to abnormal pluripotent stem cell that has given to a leukemia cell.
  • The fact that enzyme alterations have primarily occurred at the time of relapse would further substantiate that abnormalities of red cell enzymes may be the result of a derivation some circulating red cells from the abnormal pluripotent stem cell.
  • [MeSH-major] Erythrocytes, Abnormal / metabolism. Leukemia / enzymology
  • [MeSH-minor] Adolescent. Adult. Aged. Female. Humans. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / enzymology. Leukemia, Myeloid, Acute / metabolism. Male. Middle Aged. Neoplasm Recurrence, Local. Precursor Cell Lymphoblastic Leukemia-Lymphoma / enzymology. Remission Induction. Risk Factors

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  • (PMID = 16909693.001).
  • [ISSN] 0004-5772
  • [Journal-full-title] The Journal of the Association of Physicians of India
  • [ISO-abbreviation] J Assoc Physicians India
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] India
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95. Robin M, Porcher R, De Castro Araujo R, de Latour RP, Devergie A, Rocha V, Larghero J, Adès L, Ribaud P, Mary JY, Socié G: Risk factors for late infections after allogeneic hematopoietic stem cell transplantation from a matched related donor. Biol Blood Marrow Transplant; 2007 Nov;13(11):1304-12
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  • Patients transplanted for aplastic anemia, chronic myelogenous leukemia (CML), and acute myelogenous leukemia (AML) were included.
  • Thirty patients died beyond the first year, causes of death were relapse (n = 10) and infections (n = 19, associated with graft-versus-host disease [GVHD] in 16 patients).
  • Extensive cGVHD was the only risk factor for non-HCV viral infections in patients transplanted for AML or CML (HR: 2.7, 95%CI: 1.4-5.1, P = .002).
  • [MeSH-minor] Adolescent. Adult. Anemia, Aplastic / therapy. Female. France / epidemiology. Graft vs Host Disease. Humans. Incidence. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy. Leukemia, Myeloid, Acute / therapy. Male. Retrospective Studies. Risk Factors. Transplantation, Homologous / adverse effects

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  • (PMID = 17950917.001).
  • [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
  • [Publication-country] United States
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96. Sultana TA, Abdul Mottalib M, Islam S, Khan MA, Choudhury S: Rt-PCR method for diagnosis and follow-up of hematological malignancies: first approach in Bangladesh. Bangladesh Med Res Counc Bull; 2008 Apr;34(1):1-11
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  • [Title] Rt-PCR method for diagnosis and follow-up of hematological malignancies: first approach in Bangladesh.
  • Nested reverse-transcriptase polymerase chain reaction (rt-PCR) was performed on 58 leukemia patients at BIRDEM Laboratory, as a pioneering work in Bangladesh.
  • Thirty of themwere examined for the presence of BCR-ABL being clinically and morphologically diagnosed as chronic myeloid leukemia (CML) and 28 for PML-RARalpha fusion transcripts being clinically and morphologically diagnosed as acute promyelocytic leukemia (APL/ AML M3).
  • In present times, the detection of minimal residual disease in patients undergoing treatment for hematological malignancies has become an important goal, not only to monitor the effectiveness of therapy but also to detect an impending relapse.
  • [MeSH-major] Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis. Leukemia, Promyelocytic, Acute / diagnosis. Reverse Transcriptase Polymerase Chain Reaction / methods

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  • (PMID = 18783070.001).
  • [ISSN] 0377-9238
  • [Journal-full-title] Bangladesh Medical Research Council bulletin
  • [ISO-abbreviation] Bangladesh Med Res Counc Bull
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Bangladesh
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 5688UTC01R / Tretinoin; 8A1O1M485B / Imatinib Mesylate
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97. Porter DL, Antin JH: Donor leukocyte infusions in myeloid malignancies: new strategies. Best Pract Res Clin Haematol; 2006;19(4):737-55
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  • Donor leukocyte infusion (DLI) provides direct and potent graft-versus-leukemia (GVL) activity to treat relapse after allogeneic stem-cell transplantation.
  • DLI is dramatically effective for relapsed chronic myelogenous leukemia (CML), but has been less effective for relapse of other myeloid malignancies.
  • Nevertheless, most recipients of DLI for relapsed CML, and many patients with relapsed acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), will experience prolonged remissions and probable cure.
  • Ultimately, the identification of the effector cells and target antigens for GVL induction will lead to the use of tumor-specific adoptive immunotherapy to both prevent and treat relapse with minimal toxicity.
  • Although many issues remain unsettled, the potential to harness the graft-versus-leukemia activity of allogeneic donor cells provides a powerful new paradigm for the immunotherapy of cancer.
  • [MeSH-major] Graft vs Leukemia Effect / immunology. Leukemia, Myeloid / immunology. Leukemia, Myeloid / therapy. Leukocyte Transfusion

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  • (PMID = 16997180.001).
  • [ISSN] 1521-6926
  • [Journal-full-title] Best practice & research. Clinical haematology
  • [ISO-abbreviation] Best Pract Res Clin Haematol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Number-of-references] 99
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98. Gahrton G: Risk assessment in haematopoietic stem cell transplantation: impact of donor-recipient sex combination in allogeneic transplantation. Best Pract Res Clin Haematol; 2007 Jun;20(2):219-29
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  • In large retrospective registry studies of several thousands of patients with aplastic anemia, chronic myelocytic leukemia (CML), acute myelocytic leukemia (AML), and multiple myeloma, chronic graft-versus-host disease (cGVHD) was more frequent and transplant-related mortality (TRM) higher in males with a female donor (F-->M) than in other donor-recipient sex combinations.
  • Graft rejection was more frequent in females with a male donor (M-->F) in aplastic anemia, and a graft-versus-tumor effect (GVT) was documented as a reduced relapse rate in F-->M in CML, AML and multiple myeloma.
  • The overall survival was adversely affected in F-->M in aplastic anemia, AML and CML and in M-->F in aplastic anemia.
  • [MeSH-minor] Anemia, Aplastic / therapy. Female. Graft Rejection / immunology. Graft vs Host Disease / etiology. Graft vs Host Disease / immunology. Graft vs Tumor Effect / immunology. Humans. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology. Male. Recurrence. Risk Assessment. Sex Factors. Survival Analysis

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  • (PMID = 17448958.001).
  • [ISSN] 1521-6926
  • [Journal-full-title] Best practice & research. Clinical haematology
  • [ISO-abbreviation] Best Pract Res Clin Haematol
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] England
  • [Number-of-references] 37
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99. Kornblit B, Masmas T, Madsen HO, Ryder LP, Svejgaard A, Jakobsen B, Sengeløv H, Olesen G, Heilmann C, Dickmeiss E, Petersen SL, Vindeløv L: Haematopoietic cell transplantation with non-myeloablative conditioning in Denmark: disease-specific outcome, complications and hospitalization requirements of the first 100 transplants. Bone Marrow Transplant; 2008 May;41(10):851-9
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  • We analysed the outcome and hospitalization requirements of the first 100 patients (Hodgkin's disease (HD), N=13; multiple myeloma (MM), N=14; CLL, N=12; non-Hodgkin's lymphoma (NHL), N=17; myelodysplastic syndrome (MDS), N=18; AML, N=24 and CML, N=2) treated in Denmark with haematopoietic cell transplantation after non-myeloablative conditioning with TBI 2 Gy+/-fludarabine.
  • The cumulative incidence of acute GVHD grade II-IV and extensive chronic GVHD was 67 and 49%.
  • After a median follow-up of 534 days, the overall survival, PFS, relapse-related mortality and treatment-related mortality were 59, 50, 25 and 17%, respectively.
  • Patients with CLL, NHL, AML and MDS with <5% blasts at any time had a favourable outcome with a PFS of 61-71%.
  • [MeSH-minor] Adult. Aged. Denmark / epidemiology. Female. Graft vs Host Disease / epidemiology. Hodgkin Disease / therapy. Hospitalization / statistics & numerical data. Humans. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy. Leukemia, Myeloid, Acute / therapy. Lymphoma, Non-Hodgkin / therapy. Male. Middle Aged. Multiple Myeloma / therapy. Myelodysplastic Syndromes / therapy. Outpatient Clinics, Hospital / utilization. Treatment Outcome. Vidarabine / analogs & derivatives. Vidarabine / therapeutic use. Whole-Body Irradiation

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  • (PMID = 18246114.001).
  • [ISSN] 0268-3369
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine
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100. Chen SH, Hung IJ, Yang CP, Jaing TH, Fang EC, Yang SH, Tseng CK: Allogeneic related bone marrow transplantation in children--a single center experience. Acta Paediatr Taiwan; 2005 Nov-Dec;46(6):352-5
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  • Allogeneic bone marrow grafts from 19 donors (18 human leukocyte antigen (HLA)-matched sibling donors and 1 one antigen-mismatched related donor) were transplanted into patients aged 3-17 years (16 with leukemia and 3 with non-malignant disease).
  • Acute graft versus host disease (GVHD) grade II to IV developed in 8 patients (42.
  • Six patients (31.6%) had relapse of their underlying malignant disease, and one of them is still alive.
  • Seven patients died (5 because of relapse and/or disease progression and 2 because of infectious complication).
  • The underlying diseases were acute lymphoblastic leukemia (ALL; 4 cases: 3 CR2, 1 Ph+), acute myeloid leukemia (AML; 2 cases: 1 CR2, 1 refractory), and juvenile chronic myelogenous leukemia (JCML; 1 case).
  • Relapsed leukemia at an extramedullary site occurred in 2 patients with ALL after BMT.
  • Although our data should be interpreted cautiously considering the limited number of patients, isolated extramedullary relapse seems to be common after allogeneic BMT.
  • [MeSH-minor] Adolescent. Child. Child, Preschool. Female. Humans. Leukemia / therapy. Male. Recurrence. Retrospective Studies. Transplantation, Homologous

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  • (PMID = 16640037.001).
  • [ISSN] 1608-8115
  • [Journal-full-title] Acta paediatrica Taiwanica = Taiwan er ke yi xue hui za zhi
  • [ISO-abbreviation] Acta Paediatr Taiwan
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] China (Republic : 1949- )
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