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1. Gorin NC: Autologous stem cell transplantation in acute lymphocytic leukemia. Stem Cells; 2002;20(1):3-10
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  • [Title] Autologous stem cell transplantation in acute lymphocytic leukemia.
  • Autologous stem cell transplantation (ASCT) as well as allogeneic stem cell transplantation and conventional chemotherapy (CT) are less effective at treating acute lymphocytic leukemia (ALL) than acute myelocytic leukemia (AML).
  • Statistics from the European Group for Blood and Marrow Transplantation reveal a transplant-related mortality at 5 years of 11% +/- 1%, a relapse incidence of 60% +/- 2%, and a leukemia-free survival (LFS) and overall survival (OS) of 36% +/- 2% and 42% +/- 2%, respectively in 1,366 adults autografted in first remission (CR1).
  • In contrast, multicentric and single-institution studies have found better results in adults autografted in CR1, with LFS at 5 years from 46% to 64%, possible efficacy of marrow in vitro purging with mafosfamide (LFS 52%), and improvement in outcome with additional measures post-ASCT, such as maintenance chemotherapy (LFS 57%).
  • [MeSH-major] Hematopoietic Stem Cell Transplantation / methods. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • [MeSH-minor] Adult. Child. Disease-Free Survival. Europe. Humans. Registries. Risk Factors. Time Factors

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  • (PMID = 11796917.001).
  • [ISSN] 1066-5099
  • [Journal-full-title] Stem cells (Dayton, Ohio)
  • [ISO-abbreviation] Stem Cells
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 24
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2. Chiaretti S, Li X, Gentleman R, Vitale A, Vignetti M, Mandelli F, Ritz J, Foa R: Gene expression profile of adult T-cell acute lymphocytic leukemia identifies distinct subsets of patients with different response to therapy and survival. Blood; 2004 Apr 1;103(7):2771-8
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  • [Title] Gene expression profile of adult T-cell acute lymphocytic leukemia identifies distinct subsets of patients with different response to therapy and survival.
  • Gene expression profiles were examined in 33 adult patients with T-cell acute lymphocytic leukemia (T-ALL).
  • Comparison between refractory patients and those who responded to induction chemotherapy identified a single gene, interleukin 8 (IL-8), that was highly expressed in refractory T-ALL cells and a set of 30 genes that was highly expressed in leukemic cells from patients who achieved complete remission.
  • We next identified 19 genes that were differentially expressed in T-ALL cells from patients who either had a relapse or remained in continuous complete remission.
  • This study demonstrates that gene expression profiling can identify a limited number of genes that are predictive of response to induction therapy and remission duration in adult patients with T-ALL.
  • [MeSH-major] Gene Expression Profiling / methods. Gene Expression Regulation, Neoplastic / genetics. Leukemia-Lymphoma, Adult T-Cell / genetics. Leukemia-Lymphoma, Adult T-Cell / therapy
  • [MeSH-minor] Adult. Base Sequence. DNA Primers. Humans. Models, Genetic. Oligonucleotide Array Sequence Analysis / methods. Predictive Value of Tests. Reproducibility of Results. Reverse Transcriptase Polymerase Chain Reaction / methods. Survival Rate. Time Factors. Tumor Cells, Cultured

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  • (PMID = 14684422.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA66996
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / DNA Primers
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3. Park SR, Kim JH, Kim DY, Lee S, Lee SY, Choi IS, Yoon SS, Park S, Kim BG, Kim NK: Treatment outcome of adult acute lymphocytic leukemia with VPD(L) regimen: analysis of prognostic factors. Korean J Intern Med; 2003 Mar;18(1):21-8
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  • [Title] Treatment outcome of adult acute lymphocytic leukemia with VPD(L) regimen: analysis of prognostic factors.
  • BACKGROUND: Because of the relative paucity of data regarding the clinical outcome in adult patients with acute lymphocytic leukemia (ALL) in Korea, we analyzed clinical courses in adult ALL patients treated with VPD (L) regimen (vincristine, prednisolone, daunorubicin, L-asparaginase) at the Seoul National University Hospital, and evaluated prognostic factors influencing the outcome.
  • Induction chemotherapy consisted of VPD with (46 cases) or without L-asparaginase (7 cases).
  • After complete remission (CR), consolidation therapy, CNS prophylaxis and maintenance chemotherapy were administered.
  • With a median follow-up time of 27.2 months (range 12.9-83.0 months) in living patients, the median overall survival (OS) for all cases was 16.7 months (13.4-20.1 months, 95% C.I.) and the estimated 4-year OS rate was 25.4% +/- 8.9%.
  • The median relapse-free survival (RFS) was 12.2 months (8.4-16.0 months, 95% C.I.
  • CONCLUSION: Despite an initial excellent response to the VPD (L) regimen, newer therapeutic strategies, including more intensive postremission therapies, are urgently needed because of the high relapse rate.
  • Future therapeutic approaches need to be stratified according to several prognostic factors.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Asparaginase / administration & dosage. Doxorubicin / administration & dosage. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality. Prednisone / administration & dosage. Vincristine / administration & dosage
  • [MeSH-minor] Administration, Oral. Adolescent. Adult. Aged. Disease-Free Survival. Dose-Response Relationship, Drug. Drug Administration Schedule. Female. Follow-Up Studies. Humans. Infusions, Intravenous. Male. Maximum Tolerated Dose. Middle Aged. Multivariate Analysis. Probability. Remission Induction. Retrospective Studies. Survival Analysis. Treatment Outcome

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  • (PMID = 12760264.001).
  • [ISSN] 1226-3303
  • [Journal-full-title] The Korean journal of internal medicine
  • [ISO-abbreviation] Korean J. Intern. Med.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] Korea (South)
  • [Chemical-registry-number] 5J49Q6B70F / Vincristine; 80168379AG / Doxorubicin; EC 3.5.1.1 / Asparaginase; VB0R961HZT / Prednisone; VPD protocol
  • [Other-IDs] NLM/ PMC4531597
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4. Ohashi H, Kato C, Fukami S, Saito H, Hamaguchi M: Leukemic relapse in the central nervous system after allogeneic stem cell transplantation with complete remission in the bone marrow and donor-type chimerism: report of two cases. Am J Hematol; 2005 Jun;79(2):142-6
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  • [Title] Leukemic relapse in the central nervous system after allogeneic stem cell transplantation with complete remission in the bone marrow and donor-type chimerism: report of two cases.
  • We studied two cases with leukemia that relapsed in the central nervous system (CNS) after allogeneic stem cell transplantation.
  • One patient underwent peripheral blood stem cell transplantation (SCT) from a related, yet haplotype-mismatched, donor for chronic myelomonocytic leukemia.
  • She was kept in complete remission (CR) in the bone marrow (BM) for 7 months, until relapse in the cerebrospinal fluid (CSF) was evident.
  • In the other patient, with acute lymphoblastic leukemia, systemic relapse occurred when he was still on immunosuppression 6 months after SCT from an unrelated donor.
  • After induction chemotherapy following cessation of immunosuppression, the BM examination proved CR.
  • During consolidation chemotherapy, however, he developed leukemic dissemination in the CSF, despite the fact that the BM was in CR.
  • In both patients, the BM cells and all the fractions of the PB cells proved donor-type chimeras.
  • These results seem to suggest that the graft-versus-leukemia effects might not be as effective in the CNS as in the BM, even when complete T-lymphoid chimerism is achieved.
  • [MeSH-major] Bone Marrow / pathology. Central Nervous System Neoplasms / therapy. Leukemia / therapy. Neoplasm Recurrence, Local. Peripheral Blood Stem Cell Transplantation. Tissue Donors. Transplantation Chimera
  • [MeSH-minor] Adult. Female. Humans. Leukemia, Lymphocytic, Chronic, B-Cell / pathology. Leukemia, Lymphocytic, Chronic, B-Cell / therapy. Leukemia, Myelomonocytic, Chronic / pathology. Leukemia, Myelomonocytic, Chronic / therapy. Male. Middle Aged. Remission Induction. Transplantation, Homologous

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  • (PMID = 15929112.001).
  • [ISSN] 0361-8609
  • [Journal-full-title] American journal of hematology
  • [ISO-abbreviation] Am. J. Hematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
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5. Kendall HE, Vacek PM, Finette BA: Analysis of microsatellite instability in children treated for acute lymphocytic leukemia with elevated HPRT mutant frequencies. Mutagenesis; 2004 Sep;19(5):409-12
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  • [Title] Analysis of microsatellite instability in children treated for acute lymphocytic leukemia with elevated HPRT mutant frequencies.
  • Survival rates of children treated for cancer have increased dramatically over the last 25 years following the development of risk-directed multi-modality treatment protocols.
  • We have previously observed that children treated for acute lymphocytic leukemia (ALL) have significantly increased somatic mutant frequencies (Mfs) (30- to 1300-fold higher) at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) reporter gene in their non-malignant peripheral T cells compared with children at diagnosis or controls.
  • In order to gain insight into the etiology of the observed dramatic increase in Mfs following antineoplastic therapy, we investigated the prevalence of microsatellite instability (MSI), reflective of a defect in DNA mismatch repair (MMR), in children with ALL at diagnosis, during and after chemotherapy and compared them with healthy age-matched controls.
  • High-frequency MSI (MSI-high) was identified in 2 healthy children (5%) and in 2 of 20 ALL subjects at the time of disease recurrence (relapse) (10%).
  • There was no statistically significant difference between the prevalence of MSI-high in patients at the time of ALL relapse and healthy children, nor between the children with ALL at other time points and healthy children.
  • However, in a small number of patients chemotherapy may play a role in the selection of cells with defects in MMR that may have long-term clinical implications.
  • [MeSH-major] Microsatellite Repeats. Mutation. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy

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  • (PMID = 15388815.001).
  • [ISSN] 0267-8357
  • [Journal-full-title] Mutagenesis
  • [ISO-abbreviation] Mutagenesis
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / 1K01 CA 77737; United States / NCRR NIH HHS / RR / 1P20 RR 16462; United States / NCI NIH HHS / CA / 1R01 CA 090940-13; United States / NICHD NIH HHS / HD / 1R29 HD 35309; United States / NCI NIH HHS / CA / P30 CA 22435
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] England
  • [Chemical-registry-number] EC 2.4.2.8 / Hypoxanthine Phosphoribosyltransferase
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6. Eby GA: Treatment of acute lymphocytic leukemia using zinc adjuvant with chemotherapy and radiation--a case history and hypothesis. Med Hypotheses; 2005;64(6):1124-6
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  • [Title] Treatment of acute lymphocytic leukemia using zinc adjuvant with chemotherapy and radiation--a case history and hypothesis.
  • Low blood levels of zinc are often noted in acute lymphocytic leukemia (ALL), but zinc is not administered as part of any modern chemotherapy program in the treatment of ALL.
  • Upon noting low blood levels of zinc in a 3-year-old 11.3 kg girl, zinc at the rate of 3.18 mg/kg body weight/day was administered from the start of chemotherapy through the full 3 years of maintenance therapy.
  • The result was a bone marrow remission from 95+% blast cells to an observed zero blast cell count in both hips within the first 14 days of treatment which never relapsed.
  • There were no side effects from zinc or chemotherapy at any time, and zinc is hypothesized to have improved the patient's overall ability to withstand toxic effects of chemotherapy.
  • This report identifies zinc treatment as being vital to rapid and permanent recovery from ALL.
  • The extremely broad role of zinc in pre-leukemic adverse health conditions, viral, fungal and tumoral immunity, hemopoietics, cell growth, division and differentiation, genetics and chemotherapy interactions are considered.
  • If a nutrient such as zinc could be shown to strengthen the function of chemotherapy and immune function, then it could be hypothesized that the relapse rate would be lessened since the relapse rate is related to both the rate at which a remission is obtained and the thoroughness of the elimination of leukemic blasts.
  • Since treatment with zinc and other identified deficient nutrients, particularly magnesium, did not appear injurious in ALL and they appear to be highly beneficial, controlled clinical studies of zinc (3.18 mg/kg body weight/day) with magnesium (8.0 mg/kg body weight/day) as adjuvants to chemotherapy in the treatment of childhood ALL are suggested.
  • Treatment with zinc adjuvant is hypothesized to accelerate recovery from ALL, and in conjunction with chemotherapy, cure ALL.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Gluconates / therapeutic use. Leukemia-Lymphoma, Adult T-Cell / drug therapy. Zinc / physiology
  • [MeSH-minor] 6-Mercaptopurine / administration & dosage. Bone Marrow / drug effects. Bone Marrow / pathology. Chemotherapy, Adjuvant. Chickenpox Vaccine / immunology. Child, Preschool. Combined Modality Therapy. Cranial Irradiation. Dietary Supplements. Drug Synergism. Female. Humans. Immune System / drug effects. Magnesium Deficiency / etiology. Methotrexate / administration & dosage. Models, Biological. Prednisone / administration & dosage. Radiotherapy, Adjuvant. Remission Induction. Survivors. Vincristine / administration & dosage

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  • (PMID = 15823699.001).
  • [ISSN] 0306-9877
  • [Journal-full-title] Medical hypotheses
  • [ISO-abbreviation] Med. Hypotheses
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Scotland
  • [Chemical-registry-number] 0 / Chickenpox Vaccine; 0 / Gluconates; 5J49Q6B70F / Vincristine; E7WED276I5 / 6-Mercaptopurine; J41CSQ7QDS / Zinc; R4R8J0Q44B / gluconic acid; VB0R961HZT / Prednisone; YL5FZ2Y5U1 / Methotrexate
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7. Thomas DA: Philadelphia chromosome positive acute lymphocytic leukemia: a new era of challenges. Hematology Am Soc Hematol Educ Program; 2007;:435-43
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  • [Title] Philadelphia chromosome positive acute lymphocytic leukemia: a new era of challenges.
  • Significant advances in the treatment of Philadelephia chromosome (Ph)- or BCR-ABL-positive acute lymphocytic leukemia (ALL) have been made since the discovery of the selective ABL tyrosine kinase inhibitors (TKIs).
  • Whereas the outcome with standard chemotherapy was previously dismal, incorporation of imatinib mesylate into frontline therapy has improved relapse-free and overall survival.
  • However, the emergence of resistance to imatinib presents new therapeutic challenges.
  • Optimal use of these novel agents in the treatment schema of Ph(+) ALL will be paramount in ensuring continued success in the eradication of this disease.

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  • (PMID = 18024662.001).
  • [ISSN] 1520-4391
  • [Journal-full-title] Hematology. American Society of Hematology. Education Program
  • [ISO-abbreviation] Hematology Am Soc Hematol Educ Program
  • [Language] ENG
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate
  • [Number-of-references] 66
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8. Jabbour E, Cortes J, Kantarjian HM, Giralt S, Jones D, Jones R, Giles F, Andersson BS, Champlin R, de Lima M: Allogeneic stem cell transplantation for patients with chronic myeloid leukemia and acute lymphocytic leukemia after Bcr-Abl kinase mutation-related imatinib failure. Blood; 2006 Aug 15;108(4):1421-3
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  • [Title] Allogeneic stem cell transplantation for patients with chronic myeloid leukemia and acute lymphocytic leukemia after Bcr-Abl kinase mutation-related imatinib failure.
  • Resistance to imatinib mesylate is an emerging problem in the treatment of chronic myeloid leukemia (CML), often associated with point mutations in the Bcr-Abl kinase domain.
  • Ten imatinib-resistant patients with Bcr-Abl kinase mutations received a transplant: 9 had CML (3 in chronic phase, 4 in accelerated phase, and 2 in blast phase) and 1 had Philadelphia-positive acute lymphocytic leukemia (ALL).
  • All patients engrafted; there were no treatment-related deaths.
  • Three patients (mutations Q252H, E255K, and T315I) died of relapse after Allo-SCT.
  • [MeSH-major] Drug Resistance, Neoplasm / genetics. Fusion Proteins, bcr-abl / genetics. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy. Point Mutation. Stem Cell Transplantation
  • [MeSH-minor] Adult. Benzamides. Blast Crisis / genetics. Blast Crisis / metabolism. Blast Crisis / mortality. Blast Crisis / therapy. Disease-Free Survival. Female. Graft Survival / drug effects. Graft Survival / genetics. Humans. Imatinib Mesylate. Male. Middle Aged. Piperazines / administration & dosage. Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics. Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism. Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy. Protein Kinase Inhibitors / administration & dosage. Pyrimidines / administration & dosage. Recurrence. Salvage Therapy. Transplantation, Homologous. Treatment Outcome


9. Sonabend RY, McKay SV, Okcu MF, Yan J, Haymond MW, Margolin JF: Hyperglycemia during induction therapy is associated with poorer survival in children with acute lymphocytic leukemia. J Pediatr; 2009 Jul;155(1):73-8
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  • [Title] Hyperglycemia during induction therapy is associated with poorer survival in children with acute lymphocytic leukemia.
  • OBJECTIVES: To investigate whether children with acute lymphocytic leukemia (ALL) who have development of hyperglycemia during induction may have worse relapse-free (RFS) and overall survival (OS) rates.
  • Blood glucose concentrations during induction therapy were reviewed; patients were assigned to 3 groups: euglycemia (blood glucose < 140 mg/dL), mild hyperglycemia (blood glucose between 140-200 mg/dL), and overt hyperglycemia (blood glucose > 200 mg/dL).
  • Patients with overt hyperglycemia had poorer RFS (68% +/- [SE] 6.7 vs 85% +/- 3.6, P = .025) and OS (74% +/- 6.1 vs 96% +/- 1.9, P < .0001) at 5 years than their counterparts.
  • Patients with overt hyperglycemia had 6.2 times (95% CI 1.6-24.7, P = .01) greater risk for death, independent of risk group and type of steroid.
  • [MeSH-major] Hyperglycemia / epidemiology. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality. Severity of Illness Index
  • [MeSH-minor] Antineoplastic Agents / therapeutic use. Asparaginase / therapeutic use. Blood Glucose / analysis. Child. Child, Preschool. Daunorubicin / therapeutic use. Dexamethasone / therapeutic use. Escherichia coli / enzymology. Female. Glucocorticoids / therapeutic use. Humans. Male. Neoplasm Recurrence, Local / epidemiology. Prednisone / therapeutic use. Vincristine / therapeutic use

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  • [CommentIn] J Pediatr. 2009 Jul;155(1):A2 [19559280.001]
  • (PMID = 19394046.001).
  • [ISSN] 1097-6833
  • [Journal-full-title] The Journal of pediatrics
  • [ISO-abbreviation] J. Pediatr.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Blood Glucose; 0 / Glucocorticoids; 5J49Q6B70F / Vincristine; 7S5I7G3JQL / Dexamethasone; EC 3.5.1.1 / Asparaginase; VB0R961HZT / Prednisone; ZS7284E0ZP / Daunorubicin
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10. Todeschini G: High-dose anthracycline induction in adult acute lymphocytic leukemia. Hematol Oncol Clin North Am; 2001 Feb;15(1):9-20
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  • [Title] High-dose anthracycline induction in adult acute lymphocytic leukemia.
  • Many anthracyclines seem to be essential components of chemotherapy in adult ALL patients.
  • The results of different studies suggest that 1. anthracyclines increase the probability of CR 2. complete response is obtained earlier with the use of high-dose anthracyclines 3. the optimal timing for anthracycline administration is probably the very early phase of the disease, because an earlier CR is a favorable prognostic indicator in ALL 4. high-dose DNM may be beneficial: given at high dosage in a dose-intensive way it can reduce the occurrence of relapse.
  • There is evidence from randomized and nonrandomized studies that anthracyclines increase the CR rates when added to other classic components of ALL therapy.
  • Although anthracyclines in induction are only part of a complex program of therapy for adult ALL, the dose and dose intensity of anthracyclines may become important components of the armamentarium against this devastating disease.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Antibiotics, Antineoplastic / administration & dosage. Antibiotics, Antineoplastic / adverse effects. Child. Clinical Trials as Topic. Disease-Free Survival. Drug Administration Schedule. Female. Follow-Up Studies. Heart Diseases / chemically induced. Humans. Infection / etiology. Infection / mortality. Life Tables. Male. Middle Aged. Multicenter Studies as Topic. Neutropenia / chemically induced. Randomized Controlled Trials as Topic. Remission Induction. Retrospective Studies. Risk Factors. Survival Analysis. Treatment Outcome

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  • (PMID = 11253610.001).
  • [ISSN] 0889-8588
  • [Journal-full-title] Hematology/oncology clinics of North America
  • [ISO-abbreviation] Hematol. Oncol. Clin. North Am.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibiotics, Antineoplastic
  • [Number-of-references] 42
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11. Ramanarayanan J, Mehdi S, Brodzik F, Pasquale D: Clonal evolution with +11q 13, t(1;7) and t(1;4) at relapse in a patient with Ph positive acute lymphocytic leukemia (ALL) treated with single agent front line imatinib followed by dasatinib. Hematology; 2007 Dec;12(6):505-9
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  • [Title] Clonal evolution with +11q 13, t(1;7) and t(1;4) at relapse in a patient with Ph positive acute lymphocytic leukemia (ALL) treated with single agent front line imatinib followed by dasatinib.
  • Imatinib, a selective ABL kinase inhibitor has improved therapeutic outcome in patients with Philadelphia positive chronic or acute leukemia.
  • In the present study, we describe a 56-year-old male with Philadelphia chromosome positive acute lymphocytic leukemia (ALL) who was treated with up-front single agent imatinib and achieved complete hematologic, cytogenetic and molecular remission.
  • At relapse 11 months later, new chromosomal translocations involving chromosomes 1, 7 and 4 and cryptic addition to chromosome 11 were identified in Ph+ cells and the patient had rapid deterioration with progressive disease.
  • The significance of additional chromosomal abnormalities in imatinib treated patients and secondary chromosomal abnormalities in Philadelphia positive chronic myeloid leukemia and ALL are discussed briefly in this report.
  • [MeSH-major] Chromosomes, Human, Pair 11. Piperazines / therapeutic use. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics. Pyrimidines / therapeutic use. Thiazoles / therapeutic use. Translocation, Genetic

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  • (PMID = 17852464.001).
  • [ISSN] 1607-8454
  • [Journal-full-title] Hematology (Amsterdam, Netherlands)
  • [ISO-abbreviation] Hematology
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 0 / Thiazoles; 8A1O1M485B / Imatinib Mesylate; RBZ1571X5H / Dasatinib
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12. Sorror ML, Maris MB, Sandmaier BM, Storer BE, Stuart MJ, Hegenbart U, Agura E, Chauncey TR, Leis J, Pulsipher M, McSweeney P, Radich JP, Bredeson C, Bruno B, Langston A, Loken MR, Al-Ali H, Blume KG, Storb R, Maloney DG: Hematopoietic cell transplantation after nonmyeloablative conditioning for advanced chronic lymphocytic leukemia. J Clin Oncol; 2005 Jun 1;23(16):3819-29
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  • [Title] Hematopoietic cell transplantation after nonmyeloablative conditioning for advanced chronic lymphocytic leukemia.
  • PURPOSE: Patients with chemotherapy-refractory chronic lymphocytic leukemia (CLL) have a short life expectancy.
  • PATIENTS AND METHODS: Sixty-four patients diagnosed with advanced CLL were treated with nonmyeloablative conditioning (2 Gy total-body irradiation with [n = 53] or without [n = 11] fludarabine) and HCT from related (n = 44) or unrelated (n = 20) donors.
  • The incidences of grades 2, 3, and 4 acute and chronic graft-versus-host disease were 39%, 14%, 2%, and 50%, respectively.
  • All patients with morphologic CR who were tested by polymerase chain reaction (n = 11) achieved negative molecular results, and one of these patients subsequently experienced disease relapse.
  • The 2-year incidence of relapse/progression was 26%, whereas the 2-year relapse and nonrelapse mortalities were 18% and 22%, respectively.
  • Unrelated HCT resulted in higher CR and lower relapse rates than related HCT, suggesting more effective graft-versus-leukemia activity.
  • CONCLUSION: CLL is susceptible to graft-versus-leukemia effects, and allogeneic HCT after nonmyeloablative conditioning might prolong median survival for patients with advanced CLL.

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  • (PMID = 15809448.001).
  • [ISSN] 0732-183X
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / CA18029; United States / NCI NIH HHS / CA / CA78902; United States / NCI NIH HHS / CA / CA92058; United States / NCI NIH HHS / CA / CA49605; United States / NCI NIH HHS / CA / CA15704; United States / NCI NIH HHS / CA / P01 CA078902
  • [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, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine
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13. Radich JP: Philadelphia chromosome-positive acute lymphocytic leukemia. Hematol Oncol Clin North Am; 2001 Feb;15(1):21-36
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Philadelphia chromosome-positive acute lymphocytic leukemia.
  • Further characterization of molecular subtypes of Ph+ ALL may in the future distinguish those few patients with a potentially good outcome from the majority who face inevitable relapse.
  • Also, novel targeted biologic therapy especially in combination with aggressive, early chemotherapy, may soon be able to temper the disease.
  • For those without a donor, following the disease by PCR-based techniques may detect early relapse.
  • [MeSH-major] Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • [MeSH-minor] Adult. Animals. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Biomarkers, Tumor. Bone Marrow Transplantation. Cell Lineage. Cell Transformation, Neoplastic / genetics. Child. Disease-Free Survival. Fusion Proteins, bcr-abl / analysis. Fusion Proteins, bcr-abl / genetics. Fusion Proteins, bcr-abl / physiology. Humans. Leukemia, Experimental / genetics. Mice. Mice, Transgenic. Neoplasm Transplantation. Neoplasm, Residual. Philadelphia Chromosome. Phosphorylation. Prognosis. Protein Processing, Post-Translational. Transplantation, Homologous. Treatment Outcome

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  • (PMID = 11258387.001).
  • [ISSN] 0889-8588
  • [Journal-full-title] Hematology/oncology clinics of North America
  • [ISO-abbreviation] Hematol. Oncol. Clin. North Am.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA 18029
  • [Publication-type] Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; EC 2.7.10.2 / Fusion Proteins, bcr-abl
  • [Number-of-references] 77
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14. Martin TG, Linker CA: Autologous stem cell transplantation for acute lymphocytic leukemia in adults. Hematol Oncol Clin North Am; 2001 Feb;15(1):121-43
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Autologous stem cell transplantation for acute lymphocytic leukemia in adults.
  • Autologous bone marrow transplantation remains an investigational treatment for adult ALL.
  • Candidates for autoBMT include adult patients in first CR with adverse risk factors and all patients who have experienced disease relapse.
  • It remains debatable which preparative regimen is optimal, whether purging is necessary, or if chemotherapy or immunotherapy administered after transplantation can decrease disease relapse.
  • These trials should compare autologous transplantation to newer more intensive chemotherapy regimens and should take into account the heterogeneity of ALL.
  • A quality of life analysis should be performed as one high-dose treatment may be less toxic and better tolerated than multiple cycles of consolidation chemotherapy.
  • Strategies aimed at enhancing an autologous graft-versus-leukemia effect after transplantation may enhance long-term survival.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy. Transplantation, Autologous
  • [MeSH-minor] Adult. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Bone Marrow Purging. Bone Marrow Transplantation. Clinical Trials as Topic. Combined Modality Therapy. Humans. Immunophenotyping. Karyotyping. Life Tables. Multicenter Studies as Topic. Organ Specificity. Prognosis. Recurrence. Remission Induction. Risk Factors. Salvage Therapy. Survival Analysis. Transplantation Conditioning. Treatment Outcome

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  • (PMID = 11253604.001).
  • [ISSN] 0889-8588
  • [Journal-full-title] Hematology/oncology clinics of North America
  • [ISO-abbreviation] Hematol. Oncol. Clin. North Am.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 91
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15. Weiss M: Induction therapy of adult acute lymphocytic leukemia without the use of vincristine or prednisone. Hematol Oncol Clin North Am; 2001 Feb;15(1):1-7, v
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Induction therapy of adult acute lymphocytic leukemia without the use of vincristine or prednisone.
  • In the last 30 years, a multitude of treatment regimens for adult acute lymphocytic leukemia (ALL) has been developed.
  • Essentially, all of these regimens use an induction therapy vincristine, prednisone, and an anthracycline intensified with L-asparaginase or cyclophosphamide.
  • Though such regimens induce most patients to enter a remission, relapse is frequent, and most adult patients ultimately die of their disease.
  • The author postulated that further refinements in this approach to induction therapy were unlikely to markedly improve treatment results in this disease.
  • Therefore, the author is studying a new intensive strategy using cytarabine with a single very high dose of mitoxantrone (without vincristine or prednisone) as induction therapy for adult patients with ALL.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Carmustine / administration & dosage. Clinical Trials, Phase II as Topic. Clinical Trials, Phase III as Topic. Controlled Clinical Trials as Topic. Cyclophosphamide / administration & dosage. Cytarabine / administration & dosage. Cytarabine / adverse effects. Dactinomycin / administration & dosage. Doxorubicin / administration & dosage. Etoposide / administration & dosage. Female. Filgrastim. Granulocyte Colony-Stimulating Factor / therapeutic use. Humans. Male. Mercaptopurine / administration & dosage. Methotrexate / administration & dosage. Middle Aged. Mitoxantrone / administration & dosage. Mitoxantrone / adverse effects. Multicenter Studies as Topic. Neutropenia / chemically induced. Neutropenia / prevention & control. Prednisone / administration & dosage. Prospective Studies. Randomized Controlled Trials as Topic. Recombinant Proteins. Remission Induction. Survival Analysis. Treatment Outcome. Vincristine / administration & dosage

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  • (PMID = 11253603.001).
  • [ISSN] 0889-8588
  • [Journal-full-title] Hematology/oncology clinics of North America
  • [ISO-abbreviation] Hematol. Oncol. Clin. North Am.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Recombinant Proteins; 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 1CC1JFE158 / Dactinomycin; 5J49Q6B70F / Vincristine; 6PLQ3CP4P3 / Etoposide; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; BZ114NVM5P / Mitoxantrone; E7WED276I5 / Mercaptopurine; PVI5M0M1GW / Filgrastim; U68WG3173Y / Carmustine; VB0R961HZT / Prednisone; YL5FZ2Y5U1 / Methotrexate
  • [Number-of-references] 21
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16. Li T, Xue Y, Zhang J, Chen S, Pan J, Wu Y, Wang Y, Shen J: Isodicentric 20q- in two cases of B-cell acute lymphocytic leukemia with the respective t(9;20)(p11;q11.2) and t(9;22)(q34;q11.2). Cancer Genet Cytogenet; 2008 Feb;181(1):55-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Isodicentric 20q- in two cases of B-cell acute lymphocytic leukemia with the respective t(9;20)(p11;q11.2) and t(9;22)(q34;q11.2).
  • The cytogenetic anomaly der(20)del(20)(q11.2q13.3)idic(20)(p11), or idic(20q-) in short form, has been reported in 13 cases of myelodysplastic syndrome, one case of chronic myelomonocytic leukemia, and one case of acute myeloid leukemia since 2004.
  • Here we report the cases of two patients with B-cell acute lymphocytic leukemia (ALL) having a novel idic(20q-).
  • One was a 34-year-old man with B-cell ALL whose leukemic cells at presentation had a karyotype of 45,XY,dic(9;20)(p11;q11.2); at relapse, a small marker chromosome was found coexisting with the dic(9;20).
  • Both patients died with a short survival time, despite receiving intensive chemotherapy.
  • [MeSH-major] Chromosomes, Human, Pair 20. Chromosomes, Human, Pair 22. Chromosomes, Human, Pair 9. Leukemia, B-Cell / genetics. Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics. Translocation, Genetic

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  • (PMID = 18262055.001).
  • [ISSN] 0165-4608
  • [Journal-full-title] Cancer genetics and cytogenetics
  • [ISO-abbreviation] Cancer Genet. Cytogenet.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
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17. Thomas DA, O'Brien S, Cortes J, Kantarjian H: New approaches to the management of Philadelphia-chromosome-positive acute lymphocytic leukemia. Curr Hematol Malig Rep; 2007 Jul;2(3):183-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] New approaches to the management of Philadelphia-chromosome-positive acute lymphocytic leukemia.
  • The discovery of targeted ABL tyrosine kinase inhibitors has allowed significant advances in the treatment of de novo Philadelphia chromosome (Ph)-positive ALL.
  • Whereas the outcome with standard chemotherapy was previously dismal, the use of imatinib in front-line therapy has improved relapse-free survival and overall survival, even in the absence of allogeneic stem cell transplantation in first complete remission (particularly for those with comorbidities or lack of a suitable donor).
  • However, the emergence of resistance to imatinib presents a new therapeutic challenge.
  • Optimal use of these novel agents in the treatment schema of Ph-positive ALL will be paramount in ensuring continued success in the eradication of this disease.
  • [MeSH-major] Piperazines / therapeutic use. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Protein Kinase Inhibitors / therapeutic use. Pyrimidines / therapeutic use
  • [MeSH-minor] Adult. Age Factors. Aged. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Benzamides. Clinical Trials as Topic / statistics & numerical data. Combined Modality Therapy. Disease-Free Survival. Drug Delivery Systems. Drug Resistance, Neoplasm / genetics. Fusion Proteins, bcr-abl / antagonists & inhibitors. Fusion Proteins, bcr-abl / genetics. Humans. Imatinib Mesylate. Multicenter Studies as Topic / statistics & numerical data. Recurrence. Remission Induction. Stem Cell Transplantation. Survival Analysis. Treatment Outcome

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  • (PMID = 20425368.001).
  • [ISSN] 1558-822X
  • [Journal-full-title] Current hematologic malignancy reports
  • [ISO-abbreviation] Curr Hematol Malig Rep
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Benzamides; 0 / Piperazines; 0 / Protein Kinase Inhibitors; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.2 / Fusion Proteins, bcr-abl
  • [Number-of-references] 59
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18. Moe PJ, Holen A, Nygaard R, Glomstein A, Madsen B, Hellebostad M, Stokland T, Wefring KW, Steen-Johnsen J, Nielsen B, Hapnes C, Børsting S: Methotrexate infusions as central nervous system prophylaxis in children with acute lymphocytic leukemia: the Norwegian experience. Pediatr Hematol Oncol; 2003 Apr-May;20(3):187-200
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Methotrexate infusions as central nervous system prophylaxis in children with acute lymphocytic leukemia: the Norwegian experience.
  • This study included all 690 children in Norway diagnosed as having acute lymphocytic leukemia (ALL) from July 1975 till the end of 1997.
  • From 1992, systemic therapy was considerably intensified, and, in addition, patients in a subgroup of the high-risk and very high-risk groups were given prophylactic cranial irradiation.
  • The overall findings showed that MTX significantly reduced central nervous system (CNS)-related relapses, and, in general, reinforced systemic therapy reduced significantly non-CNS relapses and deaths.
  • Forty patients (6%) developed isolated CNS relapse, 27 (4%) had combined CNS relapse, whereas 180 (26%) had non-CNS relapse.
  • When IDM and HDM were compared, the cumulative risk for isolated CNS relapse was significantly lower with HDM, 12 and 5%, respectively.
  • Of the 40 patients with isolated CNS relapse, 23 survived (58%).
  • [MeSH-major] Antimetabolites, Antineoplastic / therapeutic use. Central Nervous System Neoplasms / prevention & control. Methotrexate / therapeutic use. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • [MeSH-minor] Child. Child, Preschool. Clinical Trials as Topic. Combined Modality Therapy. Cranial Irradiation. Drug Administration Schedule. Humans. Infant. Infusion Pumps. Injections, Spinal. Neoplasm Recurrence, Local. Norway / epidemiology. Prospective Studies. Risk Factors. Survival Analysis. Time Factors. Treatment Outcome

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  • (PMID = 12637215.001).
  • [ISSN] 0888-0018
  • [Journal-full-title] Pediatric hematology and oncology
  • [ISO-abbreviation] Pediatr Hematol Oncol
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; YL5FZ2Y5U1 / Methotrexate
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19. Stripecke R, Levine AM, Pullarkat V, Cardoso AA: Immunotherapy with acute leukemia cells modified into antigen-presenting cells: ex vivo culture and gene transfer methods. Leukemia; 2002 Oct;16(10):1974-83

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Immunotherapy with acute leukemia cells modified into antigen-presenting cells: ex vivo culture and gene transfer methods.
  • Adult patients with acute leukemia have, in general, a poor prognosis, with long-term, disease-free survival achieved in only approximately one-third of cases.
  • One of the proposed mechanisms for this poor overall response is the inability of the immune system to detect and eliminate residual malignant leukemia cells, which subsequently serve as a source of leukemic relapse.
  • This review discusses the rationale of immunotherapy for acute leukemia and presents in vitro and in vivo model systems that were devised for pre-B acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML).
  • New advances in the ex vivo manipulation of acute leukemia cells are presented, which attempt to modify these cells into functional antigen-presenting cells.
  • These cells can then be used as autologous vaccines at the time of minimal residual disease after standard chemotherapy, to stimulate host immune responses against their own leukemia cells.
  • The various approaches toward this aim include incubation of leukemia cells with cytokines or growth factors and gene manipulation of these cells.
  • In particular, ex vivo culture of ALL cells with CD40 ligand, incubation of AML cells with granulocyte-macrophage colony-stimulating factor and interleukin-4 (GM-CSF/IL-4) and lentiviral transduction of ALL and AML cells for expression of immunomodulators (CD80 and GM-CSF) are current approaches under investigation for the development of autologous acute leukemia cell vaccines.
  • [MeSH-major] Antigen-Presenting Cells / immunology. Gene Transfer Techniques. Immunotherapy. Leukemia, Myeloid / therapy. Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • [MeSH-minor] Acute Disease. Adult. Cancer Vaccines / therapeutic use. Humans

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  • (PMID = 12357348.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / K01-CA87864-01; United States / NCI NIH HHS / CA / P01 CA6848
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Cancer Vaccines
  • [Number-of-references] 90
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20. Porter DL, Alyea EP, Antin JH, DeLima M, Estey E, Falkenburg JH, Hardy N, Kroeger N, Leis J, Levine J, Maloney DG, Peggs K, Rowe JM, Wayne AS, Giralt S, Bishop MR, van Besien K: NCI First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant; 2010 Nov;16(11):1467-503
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] NCI First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation.
  • Relapse is a major cause of treatment failure after allogeneic hematopoietic stem cell transplantation (alloHSCT).
  • Treatment options for relapse have been inadequate, and the majority of patients ultimately die of their disease.
  • There is no standard approach to treating relapse after alloHSCT.
  • Withdrawal of immune suppression and donor lymphocyte infusions are commonly used for all diseases; although these interventions are remarkably effective for relapsed chronic myelogenous leukemia, they have limited efficacy in other hematologic malignancies.
  • Conventional and novel chemotherapy, monoclonal antibody therapy, targeted therapies, and second transplants have been utilized in a variety of relapsed diseases, but reports on these therapies are generally anecdotal and retrospective.
  • As such, there is an immediate need for well-designed, disease-specific trials for treatment of relapse after alloHSCT.
  • This report summarizes current treatment options under investigation for relapse after alloHSCT in a disease-specific manner.
  • In addition, recommendations are provided for specific areas of research necessary in the treatment of relapse after alloHSCT.
  • [MeSH-major] Hematologic Neoplasms / therapy. Hematopoietic Stem Cell Transplantation. Neoplasm Recurrence, Local / therapy
  • [MeSH-minor] Hodgkin Disease / therapy. Humans. Leukemia, Lymphocytic, Chronic, B-Cell / therapy. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy. Leukemia, Myeloid, Acute / therapy. Lymphocyte Transfusion. Lymphoma, Non-Hodgkin. Multiple Myeloma / therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy. Recurrence. Transplantation, Homologous. Treatment Failure

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  • [Copyright] Copyright © 2010 American Society for Blood and Marrow Transplantation. All rights reserved.
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  • (PMID = 20699125.001).
  • [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 CA117879
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Other-IDs] NLM/ NIHMS241037; NLM/ PMC2955517
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21. Durrant IJ, Richards SM, Prentice HG, Goldstone AH: The Medical Research Council trials in adult acute lymphocytic leukemia. Hematol Oncol Clin North Am; 2000 Dec;14(6):1327-52
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  • [Title] The Medical Research Council trials in adult acute lymphocytic leukemia.
  • With a low proportion of all adults entered into randomized trials, one cannot be certain that improvements result from treatment rather than patient selection.
  • Only recently have randomized trials in adults become large enough to detect plausible treatment effects.
  • The authors believe that the main contribution of these trials so far, confirmed by other groups, is in examining prognostic features in al patients and finding that age and the presence of the Ph chromosome, independent of WBC count, gender, and cell type, is the main feature for predicting outcome.
  • Preliminary data suggest that all Ph-positive patients should undergo some sort of allograft early after CR is achieved, because these patients are not rescued by BMT after relapse.
  • At the time of the publication of this article, preliminary studies suggest that STIs may not be as effective in Ph-positive ALL as in chronic granulocytic leukemia.
  • [MeSH-major] Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • [MeSH-minor] Adolescent. Adult. Age Factors. Animals. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Bone Marrow Transplantation. Central Nervous System Neoplasms / prevention & control. Clinical Trials as Topic / methods. Combined Modality Therapy. Cranial Irradiation. Data Collection. Forecasting. Humans. Middle Aged. Multicenter Studies as Topic / methods. Neoplasm, Residual. Philadelphia Chromosome. Randomized Controlled Trials as Topic. Remission Induction. Survival Analysis. Transplantation, Homologous. Treatment Outcome. United Kingdom / epidemiology

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  • (PMID = 11147226.001).
  • [ISSN] 0889-8588
  • [Journal-full-title] Hematology/oncology clinics of North America
  • [ISO-abbreviation] Hematol. Oncol. Clin. North Am.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 30
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22. Gorin NC: Autologous stem cell transplantation for adult acute leukemia. Curr Opin Oncol; 2002 Mar;14(2):152-9
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  • [Title] Autologous stem cell transplantation for adult acute leukemia.
  • Autologous stem cell transplantation using marrow or peripheral blood is routinely used to consolidate patients with acute myelocytic leukemia in complete remission.
  • The situation is less clear for adult acute lymphocytic leukemia in which results achieved with all strategies are disappointing.
  • In acute myelocytic leukemia, autografts should be done in patients with good and standard risk factors.
  • Patients with high-risk acute myelocytic leukemia defined by poor cytogenetics or failure to achieve remission with the first induction course, should proceed to allogeneic stem cell transplantation with the best available human leukocyte antigen-identical donor (family or unrelated), and the nature of the conditioning regimen (myelo-ablative or non-myelo-ablative) should be decided in relation to age, and the patient's clinical condition.
  • Results of autografting in acute myelocytic leukemia rely strongly on the quality of the graft.
  • Higher doses of infused stem cells translate into lower relapse rates.
  • Marrow purging with cyclophosphamide derivatives also diminishes the relapse incidence.
  • In good-risk acute myelocytic leukemia, autografting is superior to high-dose ARA-C; in standard-risk acute myelocytic leukemia, both are supposedly equivalent.
  • In adult acute lymphocytic leukemia, good-risk patients get the best benefit from autografting over conventional chemotherapy.
  • Maintenance chemotherapy after transplant is likely to bring benefit.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy

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  • (PMID = 11880704.001).
  • [ISSN] 1040-8746
  • [Journal-full-title] Current opinion in oncology
  • [ISO-abbreviation] Curr Opin Oncol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 51
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23. Kantarjian HM, O'Brien S, Smith TL, Cortes J, Giles FJ, Beran M, Pierce S, Huh Y, Andreeff M, Koller C, Ha CS, Keating MJ, Murphy S, Freireich EJ: Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol; 2000 Feb;18(3):547-61
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  • [Title] Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia.
  • PURPOSE: To evaluate the efficacy and toxicity of Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), a dose-intensive regimen, in adult acute lymphocytic leukemia (ALL).
  • PATIENTS AND METHODS: Adults with newly diagnosed ALL referred since 1992 were entered onto the study; treatment was initiated in 204 patients between 1992 and January 1998.
  • Mature B-cell disease (Burkitt type) was present in 9%, T-cell disease in 17%.
  • Leukocytosis of more than 30 x 10(9)/L was found in 26%, Philadelphia chromosome-positive disease in 16% (20% of patients with assessable metaphases), CNS leukemia at the time of diagnosis in 7%, and a mediastinal mass in 7%.
  • Treatment consisted of four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate (MTX) and cytarabine therapy, together with intrathecal CNS prophylaxis and supportive care with antibiotic prophylaxis and granulocyte colony-stimulating factor therapy.
  • Maintenance in patients with nonmature B-cell ALL included 2 years of treatment with mercaptopurine, MTX, vincristine, and prednisone (POMP).
  • RESULTS: Overall, 185 patients (91%) achieved complete remission (CR) and 12 (6%) died during induction therapy.
  • The incidence of CNS relapse was low (4%).
  • Previous prognostic models remained predictive for outcome with Hyper-CVAD therapy.
  • CONCLUSION: Hyper-CVAD therapy is superior to our previous regimens and should be compared with established regimens in adult ALL.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Central Nervous System Neoplasms / pathology. Cyclophosphamide / administration & dosage. Cyclophosphamide / adverse effects. Dexamethasone / administration & dosage. Dexamethasone / adverse effects. Doxorubicin / administration & dosage. Doxorubicin / adverse effects. Female. Granulocyte Colony-Stimulating Factor / administration & dosage. Humans. Leukemia, T-Cell / drug therapy. Leukemia, T-Cell / genetics. Male. Middle Aged. Risk Factors. Survival Analysis. Treatment Outcome. Vincristine / administration & dosage. Vincristine / adverse effects

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  • (PMID = 10653870.001).
  • [ISSN] 0732-183X
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Comparative Study; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 143011-72-7 / Granulocyte Colony-Stimulating Factor; 5J49Q6B70F / Vincristine; 7S5I7G3JQL / Dexamethasone; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; CVAD protocol; VAD protocol
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24. Avivi I, Rowe JM, Goldstone AH: Stem cell transplantation in adult ALL patients. Best Pract Res Clin Haematol; 2002 Dec;15(4):653-74
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Less than 40% of adult acute lymphocytic leukaemia (ALL) patients will still be alive at 5 years post-diagnosis.
  • Ways to improve patients' outcome, using high-dose therapy followed by autologous/allogeneic stem cell transplantation (SCT) in first complete remission (CR1) rather than consolidation/maintenance chemotherapy, have been investigated.
  • The largest prospective trial ever being performed in adult ALL patients, the ongoing UKALL 12/ECOG 2993 trial, is assigning all patients who have a sibling donor to receive allogeneic SCT (alloSCT) in CR1, whereas all other patients are randomized to continue chemotherapy versus autologous SCT.
  • An interim analysis of this trial seems to support an alloSCT in first CR in adult ALL patients (reflected by a significantly reduced relapse rate with an improved disease-free survival).
  • However, less than 30% of the patients have a matched sibling donor, the majority of the patients are over 40 years old, which makes them less suitable for conventional allograft, and even in those who have a matched sibling donor and are young and fit enough to receive it the treatment-related mortality (TRM) is about 20%.
  • There are enough data to suggest now that children who achieved a clinical remission but failed to obtain a molecular/immunological remission are more prone to relapse.
  • A reasonable approach is to assign all patients with a matched related donor who has failed to achieve a molecular/immunological remission to receive a conventional alloSCT, whereas all others might be randomized to receive alloSCT versus chemotherapy/autologousSCT.
  • However, by improving our ability to select those who have the highest risk for relapse, unnecessary toxicity/mortality might be prevented and the general outcome might improve.
  • [MeSH-major] Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy. Stem Cell Transplantation
  • [MeSH-minor] Adult. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Humans. Neoplasm, Residual. Prognosis. Prospective Studies. Randomized Controlled Trials as Topic. Retrospective Studies. Risk Factors. Transplantation Conditioning

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  • (PMID = 12617869.001).
  • [ISSN] 1521-6926
  • [Journal-full-title] Best practice & research. Clinical haematology
  • [ISO-abbreviation] Best Pract Res Clin Haematol
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Review
  • [Publication-country] England
  • [Number-of-references] 98
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25. Lu Y, Sun LR, Pang XY, Lu ZH, Sui AH: [Infection status and clinical significance of Epstein-Barr virus in pediatric leukemia---a report of 35 cases]. Ai Zheng; 2007 Jan;26(1):54-7
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  • [Title] [Infection status and clinical significance of Epstein-Barr virus in pediatric leukemia---a report of 35 cases].
  • This study was to detect EBV infection in pediatric leukemia, and to explore its clinical significance.
  • METHODS: EBV DNA in peripheral blood mononuclear cells in 35 pediatric leukemia patients, including 26 cases of acute lymphoblastic leukemia (ALL) (24 received initial treatment and 2 received retreatment), 8 cases of acute non-lymphocytic leukemia (ANLL) and 1 case of chronic lymphocytic leukemia (CLL), and in 14 healthy children was detected by fluorescent quantitative polymerase chain reaction (FQ-PCR).
  • Its clinical significance was analyzed according to the clinical manifestations, prednisone sensitivity test, and complete remission (CR) rate after induction chemotherapy.
  • RESULTS: EBV DNA was detected in 8 (22.86%) of the 35 pediatric leukemia patients.
  • In ALL, the rate of no response to prednisone was significantly higher in the patients with EBV infection than in the patients without EBV infection (100% vs. 26.32%, P =0.001); CR rate after induction chemotherapy was significantly lower in the patients with EBV infection than in the patients without EBV infection (28.57% vs. 84.21%, P=0.003).
  • In ANLL, the differences of CR rate and relapse rate were not significant between the patients with and without EBV infection (P=0.5).
  • CONCLUSIONS: Pediatric leukemia patients with EBV infection have higher incidence of peripheral leukocytosis and hepatosplenomegaly.
  • [MeSH-major] Epstein-Barr Virus Infections. Leukemia, Myeloid, Acute / virology. Precursor Cell Lymphoblastic Leukemia-Lymphoma / virology
  • [MeSH-minor] Antineoplastic Agents, Hormonal / therapeutic use. Child. Child, Preschool. DNA, Viral / blood. Female. Hepatomegaly / etiology. Herpesvirus 4, Human / genetics. Humans. Infant. Leukemia, Lymphocytic, Chronic, B-Cell / blood. Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy. Leukemia, Lymphocytic, Chronic, B-Cell / virology. Leukocytosis / etiology. Male. Prednisone / therapeutic use. Remission Induction. Splenomegaly / etiology

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  • (PMID = 17222368.001).
  • [Journal-full-title] Ai zheng = Aizheng = Chinese journal of cancer
  • [ISO-abbreviation] Ai Zheng
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Hormonal; 0 / DNA, Viral; VB0R961HZT / Prednisone
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26. Svingen PA, Karp JE, Krajewski S, Mesner PW Jr, Gore SD, Burke PJ, Reed JC, Lazebnik YA, Kaufmann SH: Evaluation of Apaf-1 and procaspases-2, -3, -7, -8, and -9 as potential prognostic markers in acute leukemia. Blood; 2000 Dec 01;96(12):3922-31
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Evaluation of Apaf-1 and procaspases-2, -3, -7, -8, and -9 as potential prognostic markers in acute leukemia.
  • In this study, immunoblotting was used to examine levels of apoptotic protease activating factor-1 (Apaf-1) and procaspases-2, -3, -7, -8, and -9 in bone marrow samples (at least 80% leukemia) harvested before chemotherapy from adults with newly diagnosed acute myelogenous leukemia (AML, 42 patients) and acute lymphocytic leukemia (ALL, 18 patients).
  • Levels of these polypeptides did not correlate with prognostic factors or response to induction chemotherapy.
  • In further studies, 16 paired samples (13 AML, 3 ALL), the first harvested before induction therapy and the second harvested at the time of leukemia regrowth, were also examined.
  • There were no systematic alterations in levels of Apaf-1 or procaspases at relapse compared with diagnosis.
  • These results indicate that levels of initiator caspases vary widely among different leukemia specimens but cast doubt on the hypothesis that this variation is a major determinant of drug sensitivity for acute leukemia in the clinical setting. (Blood.
  • [MeSH-major] Caspases / metabolism. Enzyme Precursors / metabolism. Leukemia / diagnosis
  • [MeSH-minor] Acute Disease. Adolescent. Adult. Aged. Antineoplastic Combined Chemotherapy Protocols / pharmacology. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Apoptotic Protease-Activating Factor 1. Biomarkers, Tumor / immunology. Biomarkers, Tumor / metabolism. Bone Marrow Cells / chemistry. Bone Marrow Cells / enzymology. Cohort Studies. HL-60 Cells. Humans. Immunoblotting. Leukemia, Myeloid / diagnosis. Leukemia, Myeloid / metabolism. Leukemia, Myeloid / therapy. Middle Aged. Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis. Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism. Prognosis. Proteins / drug effects. Proteins / immunology. Proteins / metabolism

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  • (PMID = 11090079.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / R01 CA069008; United States / NCI NIH HHS / CA / CA13106; United States / NCI NIH HHS / CA / CA55164; United States / NCI NIH HHS / CA / CA69008
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / APAF1 protein, human; 0 / Apoptotic Protease-Activating Factor 1; 0 / Biomarkers, Tumor; 0 / Enzyme Precursors; 0 / Proteins; EC 3.4.22.- / Caspases
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27. Pavletic ZS, Arrowsmith ER, Bierman PJ, Goodman SA, Vose JM, Tarantolo SR, Stein RS, Bociek G, Greer JP, Wu CD, Kollath JP, Weisenburger DD, Kessinger A, Wolff SN, Armitage JO, Bishop MR: Outcome of allogeneic stem cell transplantation for B cell chronic lymphocytic leukemia. Bone Marrow Transplant; 2000 Apr;25(7):717-22
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  • [Title] Outcome of allogeneic stem cell transplantation for B cell chronic lymphocytic leukemia.
  • The objective of this study was to describe the outcome of allogeneic stem cell transplantation (alloSCT) in a series of patients with B cell chronic lymphocytic leukemia (B-CLL).
  • The median age of the patients was 46 years, and the median number of prior chemotherapy regimens received was two.
  • The incidence of grade II-IV acute GVHD was 54%.
  • The projected 5-year FFS, OS, and relapse rates after alloSCT were 65% (95% CI, 48-88%), 62% (95% CI, 43-88%), and 5% (95%, CI 0-13%), respectively.
  • These findings demonstrate the potential of high-dose therapy and alloSCT for inducing and maintaining a remission in patients with advanced or chemorefractory B-CLL.
  • The low relapse rate may be due to an allogeneic graft-versus-leukemia effect.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation. Leukemia, Lymphocytic, Chronic, B-Cell / therapy
  • [MeSH-minor] Adult. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cohort Studies. Disease-Free Survival. Female. Graft vs Host Disease / epidemiology. Humans. Male. Middle Aged. Neoplasm Staging. Recurrence. Remission Induction. Retrospective Studies. Survival Analysis. Transplantation, Homologous. Treatment Outcome


28. Ruoppolo M, Pezzica E, Milesi R, Corti D, Mercurio P, Fragapane G: [Neuroendocrine small-cell bladder cancer: our experience]. Urologia; 2010 Oct-Dec;77 Suppl 17:64-71
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  • At the time of presentation 59% of patients have clinical stage >T2 and 56% show metastatic disease.
  • Platinum-based adjuvant chemotherapy was proposed but only two patients received the treatment.
  • The most common site of relapse and spread of disease was the peritoneum and intestinal tract, and the reason of death was uncontrolled acute hemorrhage from gastro-intestinal district.
  • CONCLUSIONS: In the absence of a prospective study, and because of the rarity of the disease, the best treatment for small-cell bladder cancer remains uncertain.
  • Neoadjuvant chemotherapy with platinum regimen plus aggressive surgical approach will be the treatment of choice.
  • The association of chemotherapy and radiotherapy should also be considered.
  • [MeSH-minor] Adenocarcinoma. Aged. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carboplatin / administration & dosage. Combined Modality Therapy. Cystectomy. Deoxycytidine / administration & dosage. Deoxycytidine / analogs & derivatives. Disease Progression. Fatal Outcome. Gastrointestinal Hemorrhage / etiology. Hematuria / etiology. Humans. Intestinal Neoplasms / complications. Intestinal Neoplasms / secondary. Leukemia, Lymphocytic, Chronic, B-Cell. Liver Neoplasms / secondary. Lymph Node Excision. Male. Middle Aged. Neoplasms, Second Primary. Peritoneal Neoplasms / secondary. Prostatic Neoplasms. Stomach Neoplasms. Survival Rate

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  • (PMID = 21308678.001).
  • [ISSN] 1724-6075
  • [Journal-full-title] Urologia
  • [ISO-abbreviation] Urologia
  • [Language] ita
  • [Publication-type] Case Reports; English Abstract; Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0W860991D6 / Deoxycytidine; B76N6SBZ8R / gemcitabine; BG3F62OND5 / Carboplatin
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29. Russo D, Piccaluga PP, Michieli M, Michelutti T, Visani G, Gugliotta L, Bonini A, Pierri I, Gobbi M, Tiribelli M, Fanin R, Piccolrovazzi S, Baccarani M: Liposomal daunorubicin (DaunoXome) for treatment of poor-risk acute leukemia. Ann Hematol; 2002 Aug;81(8):462-6
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Liposomal daunorubicin (DaunoXome) for treatment of poor-risk acute leukemia.
  • Since the liposomal preparation of daunorubicin (DNR) (DaunoXome, or DNX) is expected to be less toxic than conventional DNR, we tested DNX combined with high-dose arabinosyl cytosine (HDAC) in 42 adult poor-risk acute leukemia patients.
  • Thirty-one patients had acute non-lymphocytic leukemia (ANLL).
  • Of these, 12 patients were newly diagnosed but were not eligible for standard induction treatment, 13 were in first relapse, and 6 were in second or subsequent relapse.
  • Eleven patients had acute lymphocytic leukemia (ALL), in first (eight cases) or second (three cases) relapse.
  • We conclude that DNX, in combination with HDAC, is an effective treatment for poor-risk adult AL.
  • [MeSH-major] Daunorubicin / administration & dosage. Leukemia, Myeloid, Acute / drug therapy. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • [MeSH-minor] Adult. Aged. Antibiotics, Antineoplastic / administration & dosage. Antibiotics, Antineoplastic / adverse effects. Antibiotics, Antineoplastic / therapeutic use. Disease-Free Survival. Drug Carriers. Drug Resistance, Multiple / genetics. Female. Humans. Liposomes. Male. Middle Aged. Patient Selection. Prognosis. Risk Factors. Treatment Outcome

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  • (PMID = 12224004.001).
  • [ISSN] 0939-5555
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antibiotics, Antineoplastic; 0 / Drug Carriers; 0 / Liposomes; ZS7284E0ZP / Daunorubicin
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30. Angiolillo AL, Yu AL, Reaman G, Ingle AM, Secola R, Adamson PC: A phase II study of Campath-1H in children with relapsed or refractory acute lymphoblastic leukemia: a Children's Oncology Group report. Pediatr Blood Cancer; 2009 Dec;53(6):978-83
The Lens. Cited by Patents in .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] A phase II study of Campath-1H in children with relapsed or refractory acute lymphoblastic leukemia: a Children's Oncology Group report.
  • BACKGROUND: Despite the increasing cure rates for children with acute lymphoblastic leukemia (ALL), patients who relapse continue to have poor prognosis.
  • Campath-1H was initially administered as an intravenous infusion over 2 hr, five times per week for 1 week, then three times per week for three additional weeks.
  • Patients with stable disease or better on day 29 could continue on to combination therapy with Campath-1H, methotrexate, and 6-mercaptopurine for two additional cycles.
  • No patients received combination therapy.
  • Serum Campath-1H concentrations appeared to be somewhat lower in children with ALL compared with adult patients with chronic lymphocytic leukemia.

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  • [Cites] Blood. 2001 Sep 15;98(6):1721-6 [11535503.001]
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  • (PMID = 19637330.001).
  • [ISSN] 1545-5017
  • [Journal-full-title] Pediatric blood & cancer
  • [ISO-abbreviation] Pediatr Blood Cancer
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / U01 CA097452-09; United States / NCI NIH HHS / CA / U01 CA097452; United States / NCI NIH HHS / CA / U10 CA098413; United States / NCI NIH HHS / CA / U10 CA098543-08; None / None / / U10 CA098543-08; United States / NCI NIH HHS / CA / U-01 CA97452; United States / NCI NIH HHS / CA / CA097452-09; United States / NCI NIH HHS / CA / U10 CA098543; United States / NCI NIH HHS / CA / U-10 CA98543; United States / NCI NIH HHS / CA / U10 CA098413-08; None / None / / U10 CA098413-08
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antibodies, Neoplasm; 0 / Antineoplastic Agents; 3A189DH42V / alemtuzumab
  • [Other-IDs] NLM/ NIHMS144404; NLM/ PMC3120889
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31. Clofarabine. Drugs R D; 2004;5(4):213-7
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • In addition, the company appears to have licensed rights from the Institute that cover the development and marketing of other purine nucleoside analogues that have relevance in the treatment of leukaemia and lymphoma.
  • The US FDA granted clofarabine fast-track designation for the treatment of refractory or relapsed acute lymphoblastic leukaemia in children in September 2003.
  • Clofarabine has also been granted orphan drug status by the US FDA for the treatment of adult and paediatric patients with acute lymphocytic leukaemia (ALL) or acute myeloid leukaemia (AML).
  • In December 2001, clofarabine was granted orphan drug status in the EU for the treatment of adult and paediatric patients with ALL.
  • A single-agent phase II study has been completed in patients with acute leukaemia and myelodysplastic syndromes.
  • Results of a phase II study of clofarabine in the treatment of acute myelogenous leukaemia in older adults who are not considered suitable for intensive chemotherapy have been very positive, with a 64% response rate in these patients being reported.
  • The pivotal trial will enroll approximately 65 patients with AML considered unsuitable for intensive chemotherapy.
  • Bioenvision currently has phase II trials ongoing in adult and paediatric patients with acute leukaemia and chronic lymphocytic leukaemia (CLL).
  • In June 2003, at the 39th Annual Meeting of the American Society of Clinical Oncology (ASCO-2003), an overall response rate of 28% was reported for clofarabine therapy in heavily pretreated children with acute leukaemia.
  • In December 2003, the first of 65 patients received treatment.
  • The companies are planning to investigate the potential use of clofarabine in combination with DNA-damaging agents, because clofarabine has been shown to inhibit DNA repair and may, therefore, potentiate the effects of DNA damaging drugs.
  • A phase I/II trial of clofarabine in combination with cytarabine (Ara-C) in adult patients with first relapse AML, ALL, CML blast crisis and myelodysplastic syndrome was initiated at the University of Texas MD Anderson Cancer Centre in October 2002.
  • In addition, ILEX said it intended to develop an oral formulation of clofarabine for the treatment of colorectal cancer.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Arabinonucleosides / therapeutic use. Leukemia / drug therapy

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  • (PMID = 15230627.001).
  • [ISSN] 1174-5886
  • [Journal-full-title] Drugs in R&D
  • [ISO-abbreviation] Drugs R D
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] New Zealand
  • [Chemical-registry-number] 0 / Adenine Nucleotides; 0 / Antineoplastic Agents; 0 / Arabinonucleosides; 762RDY0Y2H / clofarabine
  • [Number-of-references] 17
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32. Blau IW, Basara N, Bischoff M, Günzelmann S, Römer E, Kirsten D, Schmetzer B, Kiehl MG, Fauser AA: Second allogeneic hematopoietic stem cell transplantation as treatment for leukemia relapsing following a first transplant. Bone Marrow Transplant; 2000 Jan;25(1):41-5
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Second allogeneic hematopoietic stem cell transplantation as treatment for leukemia relapsing following a first transplant.
  • We report 27 patients with relapsed acute or chronic leukemia who underwent a second hematopoietic stem cell transplant (HSCT) from a related or unrelated donor.
  • Seventeen patients were diagnosed with acute myelogenous leukemia (AML), six with acute lymphocytic leukemia (ALL) and four with chronic myeloid leukemia (CML).
  • Relapse was diagnosed between 1 and 45 months after the first HSCT.
  • Chemotherapy was used as reinduction for relapse after HSCT in 16 patients who had received an autologous transplant and in three who had received an allogeneic transplant, since the latter did not respond to reduction of immunosuppression to induce a graft-versus-leukemia (GVL) reaction.
  • Five of these 19 patients (26%) achieved complete remission (CR), seven patients did not respond to chemotherapy and seven achieved a partial remission (PR).
  • One patient is alive and disease-free after two allogeneic transplants (day +1538), eight patients, who relapsed after an autologous transplant followed by an allogeneic transplant (days +248 to +1140), acute myeloid leukaemia (n = 6) and chronic myeloid leukemia (n = 2) are alive and disease-free.
  • It is suggested that a second HSCT is possible for patients with leukemia relapse following the first autologous transplant.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation. Leukemia / pathology. Leukemia / therapy
  • [MeSH-minor] Acute Disease. Adult. Chronic Disease. Female. Humans. Male. Middle Aged. Recurrence. Survival Analysis. Transplantation, Homologous

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  • (PMID = 10654013.001).
  • [ISSN] 0268-3369
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] ENGLAND
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33. Borgmann A, Zinn C, Hartmann R, Herold R, Kaatsch P, Escherich G, Möricke A, Henze G, von Stackelberg A, ALL-REZ BFM Study Group: Secondary malignant neoplasms after intensive treatment of relapsed acute lymphoblastic leukaemia in childhood. Eur J Cancer; 2008 Jan;44(2):257-68

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Secondary malignant neoplasms after intensive treatment of relapsed acute lymphoblastic leukaemia in childhood.
  • PURPOSE: To investigate the cumulative incidence of and the risk factors for developing second malignant neoplasms (SMN) in children and adolescents following treatment for relapse of acute lymphocytic leukaemia (ALL).
  • METHODS: Patients (1376) up to 18 years of age with first relapse of non-B-cell ALL were treated and achieved a 2nd complete remission (CR).
  • The treatment followed trial protocol in five consecutive multicentre trials of the ALL-REZ BFM Study Group between March 1983 and December 2001.
  • The incidence of SMN was analysed, correlated with clinical and therapeutic parameters, and compared to the age-specific incidence rates of cancers as cited in German cancer registries.
  • The overall cumulative risk of SMN at 15 years (median follow-up of 13.1 years) was 1.26%+/-0.38% (SE).
  • CONCLUSIONS: Despite repeated exposure to intense frontline and relapse treatment (including multiagent chemotherapy, cranial irradiation and stem cell transplantation in some patients) the cumulative incidence of SMN was unexpectedly low, though significantly higher than in the general age-matched population.
  • The association of SMN to SCT seemed to be a secondary effect at least partially mediated by exposure to high doses of VP16 and CY given for conditioning therapy.
  • [MeSH-major] Neoplasms, Second Primary / epidemiology. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • [MeSH-minor] Adolescent. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Child. Child, Preschool. Disease-Free Survival. Female. Germany / epidemiology. Humans. Incidence. Infant. Male. Multicenter Studies as Topic. Remission Induction. Risk Factors. Secondary Prevention

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  • (PMID = 17981026.001).
  • [ISSN] 0959-8049
  • [Journal-full-title] European journal of cancer (Oxford, England : 1990)
  • [ISO-abbreviation] Eur. J. Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Investigator] Mertens R; Imbach P; Pongratz E; Rupprecht T; Henze G; Wickmann L; Otte J; Bode U; Eberl W; Pekrun A; Kirschstein M; Hofmann K; Frank R; Möbius D; Andler W; Niekrens C; Breu H; Suttorp M; Göbel U; Weinmann G; Sauerbrey A; Beck JF; Janka-Schaub G; Welte K; Kulozik A; Tautz C; Graf N; Fink FM; Zintl F; Hermann J; Rupprath G; Dupuis W; Rodehüser M; Schrappe M; Berthold F; Sternschulte W; Körholz D; Schmitt K; Selle B; Gutjahr P; Dürken M; Christiansen H; Rose M; Borkhardt A; Burdach S; Jürgens H; Scheurlen W; Eggers G; Geib R; Dickerhoff R; Bielack S; Rauh W; Niethammer D; Debatin KM; Gadner H; Dohrn B; Schlegel PG; Niggli F
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34. Ostrowska H, Hempel D, Holub M, Sokolowski J, Kloczko J: Assessment of circulating proteasome chymotrypsin-like activity in plasma of patients with acute and chronic leukemias. Clin Biochem; 2008 Nov;41(16-17):1377-83
Hazardous Substances Data Bank. CHYMOTRYPSIN .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Assessment of circulating proteasome chymotrypsin-like activity in plasma of patients with acute and chronic leukemias.
  • OBJECTIVE: We evaluated whether the proteasomal chymotrypsin-like (ChT-L) activity is increased in plasma of patients with acute lymphoblastic (ALL), acute myeloblastic (AML) and chronic lymphocytic (CLL) leukemias.
  • RESULTS: The activity was significantly (P<0.001) higher in the plasma of ALL and AML patients at the diagnosis than in healthy subjects and decreased after therapy or remained unchanged or rose during relapse.
  • By contrast, in CLL patients at the diagnosis, the activity did not differ significantly from the healthy controls.
  • CONCLUSIONS: Plasma proteasome ChT-L activity can be a useful bio-marker for patients with acute leukemia at the blast stage.
  • [MeSH-major] Chymotrypsin / blood. Leukemia / blood. Proteasome Endopeptidase Complex / blood
  • [MeSH-minor] Adolescent. Adult. Aged. Case-Control Studies. Female. Humans. Hydrolysis / drug effects. L-Lactate Dehydrogenase / blood. Leukemia, Lymphocytic, Chronic, B-Cell / blood. Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis. Leukemia, Myeloid, Acute / blood. Leukemia, Myeloid, Acute / diagnosis. Male. Middle Aged. Oligopeptides / pharmacology. Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood. Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis. Proteasome Inhibitors. Protein Subunits / metabolism. Sodium Dodecyl Sulfate / pharmacology

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  • (PMID = 18773885.001).
  • [ISSN] 1873-2933
  • [Journal-full-title] Clinical biochemistry
  • [ISO-abbreviation] Clin. Biochem.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Oligopeptides; 0 / Proteasome Inhibitors; 0 / Protein Subunits; 134381-21-8 / epoxomicin; 368GB5141J / Sodium Dodecyl Sulfate; EC 1.1.1.27 / L-Lactate Dehydrogenase; EC 3.4.21.1 / Chymotrypsin; EC 3.4.25.1 / Proteasome Endopeptidase Complex
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35. Voliotis D, Diehl V: Challenges in treating hematologic malignancies. Semin Oncol; 2002 Jun;29(3 Suppl 8):30-9
The Lens. Cited by Patents in .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • During the past 40 years substantial progress has been made in the treatment of hematologic malignancies, particularly in some subgroups of patients.
  • Prognosis is improving in patients with acute promyelocytic leukemia and, to some extent, those with acute lymphoblastic and myeloid leukemias.
  • In CLL, outside the setting of a clinical trial, it is advisable to postpone treatment until the manifestation of clinical symptoms.
  • It is yet to be determined whether treatment strategies based on new prognostic parameters such as cytogenetics can change the course of disease.
  • Nevertheless, there has been a dramatic change in therapeutic paradigms in the past few years.
  • For the first time, with the use of new cytostatic drugs and recombinant monoclonal antibodies, it is possible to achieve molecular remissions.
  • In Hodgkin's disease, which is curable when treated with radiotherapy, chemotherapy, or combined therapy, depending on the stage of disease, the focus of future studies must be on prevention of early relapse and on primary resistant disease, both of which present a very poor prognosis.
  • [MeSH-major] Hodgkin Disease / drug therapy. Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy. Lymphoma, Follicular / drug therapy
  • [MeSH-minor] Anemia / drug therapy. Anemia / etiology. Antibodies, Monoclonal / therapeutic use. Antineoplastic Agents / therapeutic use. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Epoetin Alfa. Erythropoietin / therapeutic use. Hematinics / therapeutic use. Humans. Prognosis. Quality of Life. Recombinant Proteins. Vidarabine / analogs & derivatives. Vidarabine / therapeutic use

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  • [Copyright] Copyright 2002, Elsevier Science (USA). All rights reserved.
  • (PMID = 12082652.001).
  • [ISSN] 0093-7754
  • [Journal-full-title] Seminars in oncology
  • [ISO-abbreviation] Semin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antineoplastic Agents; 0 / Hematinics; 0 / Recombinant Proteins; 11096-26-7 / Erythropoietin; 64FS3BFH5W / Epoetin Alfa; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine
  • [Number-of-references] 96
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36. Talano JM, Casper JT, Camitta BM, Keever-Taylor CA, Murray KJ, Eapen M, Pierce KL, Margolis DA: Alternative donor bone marrow transplant for children with Philadelphia chromosome ALL. Bone Marrow Transplant; 2006 Jan;37(2):135-41
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  • Children with Philadelphia chromosome positive (Ph+) acute lymphocytic leukemia (ALL) have only a 20% event-free survival when treated with chemotherapy alone.
  • Four developed grades III-IV acute GVHD.
  • Three of 24 evaluable patients developed extensive chronic GVHD.
  • Two patients died of relapse (7%).
  • Five of six patients in >CR2 or relapse at the time of transplant died.
  • [MeSH-major] Bone Marrow Transplantation. Donor Selection. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy. Transplantation Conditioning

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  • (PMID = 16273115.001).
  • [ISSN] 0268-3369
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Immunosuppressive Agents; 04079A1RDZ / Cytarabine; 8N3DW7272P / Cyclophosphamide
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37. Khouri IF, Saliba RM, Giralt SA, Lee MS, Okoroji GJ, Hagemeister FB, Korbling M, Younes A, Ippoliti C, Gajewski JL, McLaughlin P, Anderlini P, Donato ML, Cabanillas FF, Champlin RE: Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood; 2001 Dec 15;98(13):3595-9
The Lens. Cited by Patents in .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality.
  • All patients had follicular or small cell lymphocytic lymphoma after relapse from a prior response to conventional chemotherapy.
  • Nine patients received rituximab in addition to the chemotherapy.
  • The cumulative incidence of acute grade II to IV GVHD was 20%.
  • Only one patient developed acute GVHD of greater than grade II.
  • None have had a relapse of disease, with a median follow-up period of 21 months.
  • Nonablative chemotherapy with fludarabine/cyclophosphamide followed by allogeneic stem cell transplantation is a promising therapy for indolent lymphoma with minimal toxicity and myelosuppression.
  • Further studies are warranted to compare nonablative allogeneic hematopoietic transplantation with alternative treatment strategies.
  • [MeSH-major] Graft vs Host Disease / epidemiology. Hematopoietic Stem Cell Transplantation. Immunotherapy, Adoptive. Leukemia, Lymphocytic, Chronic, B-Cell / therapy. Transplantation Conditioning / methods. Vidarabine / analogs & derivatives
  • [MeSH-minor] Adult. Aged. Antibodies, Monoclonal / administration & dosage. Antibodies, Monoclonal, Murine-Derived. Cyclophosphamide / administration & dosage. Female. Graft Survival. Graft vs Tumor Effect. Humans. Immunosuppressive Agents / administration & dosage. Lymphoma, Follicular / mortality. Lymphoma, Follicular / therapy. Male. Methotrexate / therapeutic use. Middle Aged. Platelet Transfusion. Recurrence. Remission Induction. Rituximab. Tacrolimus / therapeutic use. Transplantation, Homologous. Treatment Outcome

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  • (PMID = 11739162.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Immunosuppressive Agents; 4F4X42SYQ6 / Rituximab; 8N3DW7272P / Cyclophosphamide; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine; WM0HAQ4WNM / Tacrolimus; YL5FZ2Y5U1 / Methotrexate
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38. Chi CC, Wang SH: Disseminated cutaneous Fusarium moniliforme infections in a leukemic child. Int J Dermatol; 2007 May;46(5):487-9
Hazardous Substances Data Bank. Itraconazole .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • A 5-year-old boy had a 10-month remission of acute lymphocytic leukemia (ALL) after chemotherapy.
  • Re-induction chemotherapy was performed for relapse of ALL.
  • The skin lesions gradually healed and the fever subsided 2 weeks after the initiation of therapy with amphotericin B 30 mg and itraconazole 200 mg daily.
  • Meanwhile, relapse of leukemia was detected by hemogram showing atypical leukocytosis (WBC count of 24,400 x 10(9)/L, with blast cells representing 78%).
  • A course of chemotherapy with cytarabine, mitoxantrone, and VP-16 was prescribed, subsequently resulting in neutropenia (WBC count, < 0.1 x 10(9)/L; neutrophil count, 0/L) and spiking fever.
  • Although the aforementioned antifungal therapy was continued, the centers of the originally healed lesions turned dusky red, swollen, necrotic, and ulcerative.
  • [MeSH-major] Dermatomycoses / pathology. Fusarium / isolation & purification. Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications
  • [MeSH-minor] Amphotericin B / therapeutic use. Antifungal Agents / therapeutic use. Child. Child, Preschool. Fatal Outcome. Humans. Itraconazole / therapeutic use. Male. Neoplasm Recurrence, Local

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  • (PMID = 17472677.001).
  • [ISSN] 0011-9059
  • [Journal-full-title] International journal of dermatology
  • [ISO-abbreviation] Int. J. Dermatol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antifungal Agents; 304NUG5GF4 / Itraconazole; 7XU7A7DROE / Amphotericin B
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39. Kiratli H, Balci KE, Himmetoğlu C, Uner A: Isolated extraocular muscle involvement as the ophthalmic manifestation of leukaemia. Clin Exp Ophthalmol; 2009 Aug;37(6):609-13
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Demographic data, clinical information on the systemic disease, prominent ocular signs and symptoms, computed tomography and magnetic resonance imaging characteristics, treatments applied and the outcomes were collected.
  • Acute myeloid leukaemia was the diagnosis in two patients, and chronic lymphocytic leukaemia, chronic myeloid leukaemia and biphenotypic acute leukaemia were found in one patient each, respectively.
  • In one patient who had no prior history of leukaemia, an incisional biopsy established the diagnosis.
  • All patients received multi-agent chemotherapy.
  • CONCLUSIONS: Leukaemic infiltration of extraocular muscles is a rare and late manifestation of the advanced disease associated with relapse and there seems to be a predilection for the lateral rectus muscle.
  • Systemic prognosis remains dismal despite intensive chemotherapy.
  • [MeSH-major] Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis. Leukemia, Myeloid, Acute / diagnosis. Leukemic Infiltration. Oculomotor Muscles / pathology. Orbital Neoplasms / diagnosis
  • [MeSH-minor] Child. Child, Preschool. Female. Humans. Magnetic Resonance Imaging. Male. Middle Aged. Ocular Motility Disorders / diagnosis. Prognosis. Retrospective Studies. Tomography, X-Ray Computed

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  • [CommentIn] Clin Exp Ophthalmol. 2010 Aug;38(6):651 [20553299.001]
  • (PMID = 19702712.001).
  • [ISSN] 1442-9071
  • [Journal-full-title] Clinical & experimental ophthalmology
  • [ISO-abbreviation] Clin. Experiment. Ophthalmol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Australia
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40. Moe PJ, Holen A: High-dose methotrexate in childhood all. Pediatr Hematol Oncol; 2000 Dec;17(8):615-22
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  • An event-free survival is currently achieved in 70-80% of children diagnosed with acute lymphocytic leukemia (ALL).
  • A decline in the long-term sequalae from therapy is a challenge at present.
  • Due to the high incidence of central nervous system (CNS) relapse in ALL patients, cranial irradiation was introduced as a prophylactic measure in the beginning of the 1970s.
  • In a study from Norway, high-dose methotrexate (6-8 g/m2) was used, and only two (2.2%) of 89 ALL cases showed CNS relapse, both of reversible kind.
  • Results published so far are based on a segment of cases characterized by standard risk and white blood cell count below 50 x 10(9); a 4% reduction in CNS relapse was found for high-dose methotrexate in comparison to those treated only with long-term intrathecal methotrexate.
  • Rescue therapy with folinic acid is usually started 36 h after initiating the methotrexate infusion.
  • [MeSH-major] Antimetabolites, Antineoplastic / administration & dosage. Methotrexate / administration & dosage. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • [MeSH-minor] Central Nervous System Neoplasms / prevention & control. Child. Disease-Free Survival. Drug Administration Schedule. Humans. Infusions, Intravenous. Neoplasms, Second Primary / prevention & control. Quality of Life. Time Factors

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  • (PMID = 11127393.001).
  • [ISSN] 0888-0018
  • [Journal-full-title] Pediatric hematology and oncology
  • [ISO-abbreviation] Pediatr Hematol Oncol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; YL5FZ2Y5U1 / Methotrexate
  • [Number-of-references] 21
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41. Porter DL, Levine BL, Bunin N, Stadtmauer EA, Luger SM, Goldstein S, Loren A, Phillips J, Nasta S, Perl A, Schuster S, Tsai D, Sohal A, Veloso E, Emerson S, June CH: A phase 1 trial of donor lymphocyte infusions expanded and activated ex vivo via CD3/CD28 costimulation. Blood; 2006 Feb 15;107(4):1325-31
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  • Donor lymphocyte infusions (DLIs) induce potent graft versus tumor (GVT) effects for relapsed chronic myelogenous leukemia (CML) after allogeneic stem cell transplantation (SCT) but are disappointing for other diseases.
  • We performed a phase 1 trial of ex vivo-activated DLI (aDLI) for 18 patients with relapse after SCT.
  • Patients with aggressive malignancies received induction chemotherapy, and all patients received conventional DLI (median, 1.5 x 10(8) mononuclear cells/kg) followed 12 days later by aDLI.
  • Seven patients developed acute graft versus host disease (GVHD) (5 grade I-II, 2 grade III), and 4 developed chronic GVHD.
  • Eight patients achieved complete remission, including 4 of 7 with acute lymphocytic leukemia (ALL), 2 of 4 with acute myelogenous leukemia (AML), 1 with chronic lymphocytic leukemia (CLL), and 1 of 2 with non-Hodgkin lymphoma (NHL).
  • [MeSH-major] Antigens, CD28 / blood. Antigens, CD8 / blood. Leukemia / therapy. Lymphocyte Transfusion / adverse effects. Lymphoma / therapy. Stem Cell Transplantation / adverse effects

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  • (PMID = 16269610.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, CD; 0 / Antigens, CD28; 0 / Antigens, CD8
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42. Bonovolias ID, Tsiftsoglou AS: Hemin counteracts the repression of Bcl-2 and NrF2 genes and the cell killing induced by imatinib in human Bcr-Abl(+) CML cells. Oncol Res; 2009;17(11-12):535-47
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Imatinib is a targeted selective inhibitor of chimaeric Bcr-Abl tyrosine kinase developed for effective therapy of chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL) patients.
  • Unfortunately, evidence now exists to indicate that a portion of such patients treated with imatinib acquire resistance and subsequently relapse.
  • (b) cellular heme counteracts the ability of imatinib to repress Bcl-2 and Nrf2 gene expression; and (c) inhibitors of de novo biosynthesis can be developed and combined with imatinib to enhance its antileukemic activity.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Genes, bcl-2. Hemin / pharmacology. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. NF-E2-Related Factor 2 / genetics. Piperazines / pharmacology. Pyrimidines / pharmacology
  • [MeSH-minor] Apoptosis / drug effects. Benzamides. Cell Differentiation / drug effects. Cell Line, Tumor. DNA Damage. Flow Cytometry. Fusion Proteins, bcr-abl / genetics. Humans. Imatinib Mesylate

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  • (PMID = 19806784.001).
  • [ISSN] 0965-0407
  • [Journal-full-title] Oncology research
  • [ISO-abbreviation] Oncol. Res.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / NF-E2-Related Factor 2; 0 / NFE2L2 protein, human; 0 / Piperazines; 0 / Pyrimidines; 743LRP9S7N / Hemin; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.2 / Fusion Proteins, bcr-abl
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43. Lancet JE, Rosenblatt JD, Karp JE: Farnesyltransferase inhibitors and myeloid malignancies: phase I evidence of Zarnestra activity in high-risk leukemias. Semin Hematol; 2002 Jul;39(3 Suppl 2):31-5
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  • Acute leukemia carries a poor prognosis, especially in older patients, emphasizing the need for novel therapies.
  • Reasons for treatment failure include high rates of relapse and treatment-related toxicities.
  • Farnesyltransferase inhibitors (FTIs), a new class of agents that can interfere with intracellular signaling, are good therapeutic candidates for study in these diseases, given the relatively high levels of the target enzyme, farnesyltransferase, expressed in bone marrow and by peripheral circulating lymphocytes.
  • In a phase I trial of Zarnestra in patients with high-risk leukemia (resistant or relapsed acute myeloid leukemia [AML] or acute lymphocytic leukemia [ALL], chronic myeloid leukemia [CML] in blast crisis, or AML in poor prognosis subgroups), patients experienced an overall response rate of 29%.
  • These results suggest that Zarnestra should be studied further in patients with myeloid leukemia.
  • [MeSH-major] Alkyl and Aryl Transferases / antagonists & inhibitors. Antineoplastic Agents / therapeutic use. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Acute Disease. Clinical Trials as Topic. Enzyme Inhibitors / pharmacology. Enzyme Inhibitors / therapeutic use. Farnesyltranstransferase. Humans. Leukemia / drug therapy. Signal Transduction / drug effects

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  • [Copyright] Copyright 2002, Elsevier Science (USA). All rights reserved.
  • (PMID = 12214291.001).
  • [ISSN] 0037-1963
  • [Journal-full-title] Seminars in hematology
  • [ISO-abbreviation] Semin. Hematol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / U01CA69854
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Enzyme Inhibitors; EC 2.5.- / Alkyl and Aryl Transferases; EC 2.5.1.29 / Farnesyltranstransferase
  • [Number-of-references] 21
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44. Stieglmaier J, Bremer E, Kellner C, Liebig TM, ten Cate B, Peipp M, Schulze-Koops H, Pfeiffer M, Bühring HJ, Greil J, Oduncu F, Emmerich B, Fey GH, Helfrich W: Selective induction of apoptosis in leukemic B-lymphoid cells by a CD19-specific TRAIL fusion protein. Cancer Immunol Immunother; 2008 Feb;57(2):233-46
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Although the treatment outcome of lymphoid malignancies has improved in recent years by the introduction of transplantation and antibody-based therapeutics, relapse remains a major problem.
  • Therefore, new therapeutic options are urgently needed.
  • Simultaneous treatment of CD19-positive cell lines with scFvCD19:sTRAIL and valproic acid (VPA) or Cyclosporin A induced strongly synergistic apoptosis.
  • Treatment of patient-derived acute B-lymphoblastic leukemia (B-ALL) and chronic B-lymphocytic leukemia (B-CLL) cells resulted in strong tumoricidal activity that was further enhanced by combination with VPA.
  • The pre-clinical data presented here warrant further investigation of scFvCD19:sTRAIL as a potential new therapeutic agent for CD19-positive B-lineage malignancies.
  • [MeSH-major] Antigens, CD19. Antineoplastic Agents / pharmacology. Apoptosis / drug effects. Leukemia, B-Cell / drug therapy. Recombinant Fusion Proteins / pharmacology. TNF-Related Apoptosis-Inducing Ligand
  • [MeSH-minor] Animals. Cyclosporine / administration & dosage. Drug Synergism. Female. Flow Cytometry. Humans. Immunoglobulin Fragments. Mice. Mice, SCID. Valproic Acid / administration & dosage. Xenograft Model Antitumor Assays

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  • (PMID = 17665197.001).
  • [ISSN] 0340-7004
  • [Journal-full-title] Cancer immunology, immunotherapy : CII
  • [ISO-abbreviation] Cancer Immunol. Immunother.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antigens, CD19; 0 / Antineoplastic Agents; 0 / Immunoglobulin Fragments; 0 / Recombinant Fusion Proteins; 0 / TNF-Related Apoptosis-Inducing Ligand; 0 / TNFSF10 protein, human; 614OI1Z5WI / Valproic Acid; 83HN0GTJ6D / Cyclosporine
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