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1. Estey EH, Thall PF, Cortes JE, Giles FJ, O'Brien S, Pierce SA, Wang X, Kantarjian HM, Beran M: Comparison of idarubicin + ara-C-, fludarabine + ara-C-, and topotecan + ara-C-based regimens in treatment of newly diagnosed acute myeloid leukemia, refractory anemia with excess blasts in transformation, or refractory anemia with excess blasts. Blood; 2001 Dec 15;98(13):3575-83
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  • [Title] Comparison of idarubicin + ara-C-, fludarabine + ara-C-, and topotecan + ara-C-based regimens in treatment of newly diagnosed acute myeloid leukemia, refractory anemia with excess blasts in transformation, or refractory anemia with excess blasts.
  • It has been unclear whether regimens containing topotecan + ara-C (TA) or fludarabine + ara-C (FA) +/- idarubicin are superior to regimens containing idarubicin + ara-C (IA) without either fludarabine or topotecan for treatment of newly diagnosed acute myeloid leukemia (AML), refractory anemia with excess blasts in transformation (RAEB-t), or RAEB.
  • It is unlikely that, as given here, either FA or TA is, in general, superior to IA, highlighting the need for new treatments.
  • [MeSH-major] Anemia, Refractory, with Excess of Blasts / drug therapy. Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Leukemia, Myeloid, Acute / drug therapy. Vidarabine / analogs & derivatives
  • [MeSH-minor] Cytarabine / administration & dosage. Disease-Free Survival. Humans. Idarubicin / administration & dosage. Prognosis. Recurrence. Remission Induction. Survival Rate. Time Factors. Topotecan / administration & dosage. Treatment Failure

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  • (PMID = 11739159.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial
  • [Publication-country] United States
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 7M7YKX2N15 / Topotecan; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine; ZRP63D75JW / Idarubicin
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2. Estey EH, Shen Y, Thall PF: Effect of time to complete remission on subsequent survival and disease-free survival time in AML, RAEB-t, and RAEB. Blood; 2000 Jan 1;95(1):72-7
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  • [Title] Effect of time to complete remission on subsequent survival and disease-free survival time in AML, RAEB-t, and RAEB.
  • The authors examined the relationship between the time required to enter complete remission (CR) after a first course of chemotherapy for newly diagnosed acute myeloid leukemia (AML), refractory anemia with excess blasts in transformation (RAEB-t), or refractory anemia with excess blasts (RAEB).
  • They also examined subsequent survival time and disease-free survival time after accounting for cytogenetic status, age, and treatment.
  • Anderson Cancer Center between 1980 and 1996 for whom outcomes were established after first-course therapy.
  • Of the 1101 patients, 740 (67%) were in CR after this time; 508 of these 740 (69%) have died (80% had disease recurrence before death).
  • The authors used the parametric model of Shen and Thall to estimate, in particular, T(C) (time to CR), T(C,D) (time from CR to death = residual survival after CR), and T(C,R) (residual disease-free survival [DFS] after CR) as functions of the covariates noted above and to estimate the dependence of T(C,D) and T(C,R) on T(C).
  • There was a strong inverse association between T(C) and both T(C,D) and T(C,R) (P <.001 for both) that was independent of cytogenetic status, age, or treatment.
  • The residual survival time of patients who required >50 days to enter CR was closer to the residual survival time of resistant patients than to that of patients known to be in CR within approximately 30 days of the start of treatment.
  • Time to CR is an independent predictor of residual survival and disease-free survival in patients with newly diagnosed AML who achieve CR after 1 course of chemotherapy. (Blood.
  • [MeSH-major] Anemia, Refractory, with Excess of Blasts / therapy. Leukemia, Myeloid, Acute / therapy
  • [MeSH-minor] Age Factors. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Blast Crisis. Disease-Free Survival. Follow-Up Studies. Granulocyte Colony-Stimulating Factor / therapeutic use. Humans. Recurrence. Remission Induction. Retrospective Studies. Survival Rate. Time Factors. Treatment Outcome

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  • (PMID = 10607687.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 143011-72-7 / Granulocyte Colony-Stimulating Factor
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3. Scott BL, Storer B, Loken MR, Storb R, Appelbaum FR, Deeg HJ: Pretransplantation induction chemotherapy and posttransplantation relapse in patients with advanced myelodysplastic syndrome. Biol Blood Marrow Transplant; 2005 Jan;11(1):65-73
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  • [Title] Pretransplantation induction chemotherapy and posttransplantation relapse in patients with advanced myelodysplastic syndrome.
  • Hematopoietic cell transplantation is the only curative therapy for patients with myelodysplastic syndrome (MDS).
  • However, treatment-related toxicity and, in patients with advanced MDS (refractory anemia with excess blasts [RAEB]; RAEB in transformation [RAEB-T]) or transformation to acute myeloid leukemia with multilineage dysplasia (tAML), posttransplantation relapse continue to be prevalent.
  • Induction chemotherapy (IC) has been used in an attempt to decrease the risk of posttransplantation relapse, but the benefit for posttransplantation long-term survival is uncertain.
  • Thirty-three patients (3 with RAEB, 6 with RAEB-T, and 24 with tAML) received IC before transplantation, and 92 patients (62 with RAEB, 22 with RAEB-T, and 8 with tAML) did not.
  • There was no evidence of a benefit in posttransplantation outcome associated with prior IC, either for patients with RAEB/RAEB-T or those with tAML, with either conditioning regimen.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Hematopoietic Stem Cell Transplantation / methods. Myelodysplastic Syndromes / therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Anemia, Refractory, with Excess of Blasts / therapy. Child. Child, Preschool. Female. Humans. Leukemia, Myeloid / therapy. Male. Middle Aged. Recurrence. Remission Induction / methods. Retrospective Studies. Severity of Illness Index. Survival Analysis. Treatment Outcome

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  • (PMID = 15625546.001).
  • [ISSN] 1083-8791
  • [Journal-full-title] Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • [ISO-abbreviation] Biol. Blood Marrow Transplant.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA15704; United States / NCI NIH HHS / CA / CA18029; United States / NCI NIH HHS / CA / CA87948; United States / NHLBI NIH HHS / HL / HL 36444
  • [Publication-type] Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
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4. Tsimberidou A, Estey E, Cortes J, Thomas D, Faderl S, Verstovsek S, Garcia-Manero G, Keating M, Albitar M, O'Brien S, Kantarjian H, Giles F: Gemtuzumab, fludarabine, cytarabine, and cyclosporine in patients with newly diagnosed acute myelogenous leukemia or high-risk myelodysplastic syndromes. Cancer; 2003 Mar 15;97(6):1481-7
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  • The objectives of this study were to evaluate the efficacy and toxicity of a combination regimen of gemtuzumab, fludarabine, ara-C, and the MDR modifier (cyclosporine [CyA]) in patients with previously untreated AML, refractory anemia with excess blasts (RAEB), or RAEB in transformation (RAEBT).
  • RESULTS: Fifty-nine evaluable patients were treated: 39 patients (66%) had AML and 20 patients (34%) had RAEB/RAEBT.
  • Infections complicated 38% of the courses of chemotherapy.
  • Four patients (7%) developed hepatic venoocclusive disease (VOD).
  • [MeSH-major] Aminoglycosides. Anemia, Refractory, with Excess of Blasts / drug therapy. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid, Acute / drug therapy. Vidarabine / analogs & derivatives
  • [MeSH-minor] Adult. Aged. Alanine Transaminase / analysis. Anti-Bacterial Agents / administration & dosage. Antibodies, Monoclonal / administration & dosage. Antibodies, Monoclonal, Humanized. Aspartate Aminotransferases / analysis. Cyclosporine / administration & dosage. Cytarabine / administration & dosage. Female. Humans. Hyperbilirubinemia / chemically induced. Male. Middle Aged. Survival. Treatment Outcome


5. Giraldo P, Nomdedeu B, Loscertales J, Requena C, de Paz R, Tormo M, Navarro P, Benedit P, Gasquet JA, Aranesp in Myelodysplastic Syndromes (ARM) Study Group: Darbepoetin alpha for the treatment of anemia in patients with myelodysplastic syndromes. Cancer; 2006 Dec 15;107(12):2807-16
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  • [Title] Darbepoetin alpha for the treatment of anemia in patients with myelodysplastic syndromes.
  • BACKGROUND: Anemia occurs as a comorbidity in from 80% to 85% of patients with myelodysplastic syndromes (MDS): It causes fatigue, increases transfusion needs, and reduces quality of life.
  • The median age at diagnosis was 70 years (range, 38-87 years), the median age at the initiation of DA treatment was 75 years (range, 39-91 years), and 56.8% of patients were women.
  • The median time from last ESP dose to DA initiation was 16.8 weeks (range, 0.0-159.0 weeks; <1 week in 53.1% of patients).
  • According to the French-American-British classification system (n = 81 patients), 39.5% had refractory anemia (RA), 46.9% had RA with ringed sideroblasts, 9.9% had RA with excess blasts (RAEB), 1.2% had RAEB in transformation, and 2.5% had chronic myelomonocytic leukemia.
  • The Starting DA dose was 75 microg per week in 3.7% of patients, 150 microg per week in 65.4% of patients, and 300 microg per week in 29.6% of patients (the dose was increased in 18.5% of patients and reduced in 9.9% of patients; median time to dose adjustment, 8 weeks).
  • [MeSH-major] Anemia / drug therapy. Erythropoietin / analogs & derivatives. Hematinics / therapeutic use. Myelodysplastic Syndromes / complications


6. Santini V, Fenaux P, Mufti GJ, Hellström-Lindberg E, Silverman LR, List A, Gore SD, Seymour JF, Backstrom J, Beach CL: Management and supportive care measures for adverse events in patients with myelodysplastic syndromes treated with azacitidine*. Eur J Haematol; 2010 Aug;85(2):130-8
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  • OBJECTIVE: Myelodysplastic syndrome (MDS) treatment can initially worsen patients' clinical condition and they may discontinue therapy before achieving benefit.
  • In the AZA-001 study, patients with higher-risk MDS (FAB-defined refractory anemia with excess blasts (RAEB), RAEB in transformation, or chronic myelomonocitic leukaemia and IPSS int-2 or high) were randomized to azacitidine or to conventional care regimens (CCR), which included low-dose ara-C, BSC, or intensive chemotherapy.
  • Most AEs were transient and resolved during ongoing therapy (> 83%).
  • Hematologic AEs, most frequently observed during early treatment cycles, decreased during subsequent cycles and were usually managed with dosing delays (23-29%).
  • CONCLUSION: Hematologic and non-hematologic AEs with azacitidine decreased in frequency as treatment continued.
  • Awareness of the onset, duration and management of AEs can facilitate treatment, permitting patients to continue therapy for maximum benefit.

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  • [Cites] J Clin Oncol. 2002 May 15;20(10):2429-40 [12011120.001]
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  • (PMID = 20394651.001).
  • [ISSN] 1600-0609
  • [Journal-full-title] European journal of haematology
  • [ISO-abbreviation] Eur. J. Haematol.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / CA 31946; United States / NCI NIH HHS / CA / U10 CA031946; United States / NCI NIH HHS / CA / K24 CA111717; United States / NCI NIH HHS / CA / U10 CA033601; United States / NCI NIH HHS / CA / CA 33601
  • [Publication-type] Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; M801H13NRU / Azacitidine
  • [Other-IDs] NLM/ NIHMS490297; NLM/ PMC4000014
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7. Takizawa A, Miura T, Fujinami K, Osada Y, Tanaka M, Maruta I: [A case of therapy-related leukemia/myelodysplastic syndrome following treatment of refractory testicular germ cell tumor]. Nihon Hinyokika Gakkai Zasshi; 2005 Nov;96(7):701-4
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  • [Title] [A case of therapy-related leukemia/myelodysplastic syndrome following treatment of refractory testicular germ cell tumor].
  • We report a patient with a refractory testicular non-seminomatous germ cell tumor (NSGCT) who developed therapy-related leukemia (TRL) after undergoing salvage chemotherapy and multiple operations for repeat recurrences.
  • Fifty months after the initial therapy, pancytopenia and myeloblasts were observed in the patient's peripheral blood while the patient was undergoing salvage chemotherapy for a fifth recurrence.
  • A bone marrow examination showed evidence of myelodysplastic syndrome (MDS) and refractory anemia with excess of blasts in transformation (RAEB in T) under French-America-British (FAB) classification.
  • The patient has received induction chemotherapy for TRL with Cytarabine, Daunorubicin and Fludarabine while a bone marrow transplantation has been scheduled.
  • Recently, TRL associated with chemotherapy are being reported with increasing frequency in the literature.
  • Since early detection and treatment are necessary for the management of TRL, peripheral blood examinations should be performed after a diagnosis of refractory germ cell tumor has been made.
  • [MeSH-major] Leukemia, Myeloid, Acute / etiology. Myelodysplastic Syndromes / etiology. Neoplasms, Germ Cell and Embryonal / drug therapy. Neoplasms, Second Primary / etiology. Testicular Neoplasms / drug therapy
  • [MeSH-minor] Adult. Anemia, Refractory, with Excess of Blasts / pathology. Antineoplastic Combined Chemotherapy Protocols / adverse effects. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cisplatin / administration & dosage. Cisplatin / adverse effects. Drug Administration Schedule. Etoposide / administration & dosage. Etoposide / adverse effects. Humans. Ifosfamide / administration & dosage. Ifosfamide / adverse effects. Male


8. Webb DK, Passmore SJ, Hann IM, Harrison G, Wheatley K, Chessells JM: Results of treatment of children with refractory anaemia with excess blasts (RAEB) and RAEB in transformation (RAEBt) in Great Britain 1990-99. Br J Haematol; 2002 Apr;117(1):33-9
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  • [Title] Results of treatment of children with refractory anaemia with excess blasts (RAEB) and RAEB in transformation (RAEBt) in Great Britain 1990-99.
  • Between 1990 and 1999, 36 children with refractory anaemia with excess blasts (RAEB) and RAEB in transformation (RAEBt), not associated with Down's syndrome, were diagnosed in Britain.
  • A total of 31 children received intensive chemotherapy, six of whom proceeded to a bone marrow allograft in first remission, whereas two received an autograft.
  • Of the 23 given chemotherapy only, four died of toxicity, 10 relapsed and nine are alive in first remission.
  • Two children received an allograft without prior chemotherapy but died of toxicity.
  • The overall survival was 51% at 5 years, and was superior in children with RAEBt (63%) compared with RAEB (28%, P = 0.03).
  • Allowing for cytogenetics, outcomes of therapy appear similar to those for de novo acute myeloid leukaemia (AML), and it is appropriate for children with RAEB/RAEBt to be registered in AML trials.
  • [MeSH-major] Anemia, Refractory, with Excess of Blasts / therapy. Bone Marrow Transplantation
  • [MeSH-minor] Acute Disease. Adolescent. Child. Child, Preschool. Chromosomes, Human, Pair 7. Female. Humans. Infant. Leukemia, Myeloid / mortality. Leukemia, Myeloid / therapy. Male. Monosomy. Patient Selection. Randomized Controlled Trials as Topic. Survival Rate. Transplantation, Homologous. Treatment Outcome

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  • (PMID = 11918530.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Number-of-references] 30
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9. Saito K, Nakamura Y, Aoyagi M, Waga K, Yamamoto K, Aoyagi A, Inoue F, Nakamura Y, Arai Y, Tadokoro J, Handa T, Tsurumi S, Arai H, Kawagoe Y, Gunnji H, Kitsukawa Y, Takahashi W, Furusawa S: Low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (CAG regimen) for previously treated patients with relapsed or primary resistant acute myelogenous leukemia (AML) and previously untreated elderly patients with AML, secondary AML, and refractory anemia with excess blasts in transformation. Int J Hematol; 2000 Apr;71(3):238-44
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  • [Title] Low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (CAG regimen) for previously treated patients with relapsed or primary resistant acute myelogenous leukemia (AML) and previously untreated elderly patients with AML, secondary AML, and refractory anemia with excess blasts in transformation.
  • We used the CAG regimen (low-dose cytarabine [10 mg/m2 per 12 hours, days 1-14], aclarubicin [14 mg/m2 per day, days 1-4], and granulocyte colony-stimulating factor [200 micrograms/m2 per day, days 1-14]) for the treatment of patients with primary resistant acute myelogenous leukemia (AML) and previously untreated elderly patients with AML, secondary AML, and refractory anemia with excess blasts in transformation (RAEB-T) in addition to relapsed AML.
  • Forty-three of 69 (62%) patients achieved complete remission (CR), including 29 of 35 (83%) patients with relapsed AML, 1 of 8 patients with primary resistant AML, 5 of 8 elderly patients with previously untreated AML, and 8 of 18 patients with previously untreated secondary AML or RAEB-T.
  • The patients who achieved CR received at least 1 course of modified CAG therapy as the first consolidation therapy, followed by various second consolidation and intensification therapies.
  • The median disease-free survival and overall survival were 8 and 15 months, respectively, for relapsed AML; 11 and 8 months for the elderly patients; and 8 and 17 months for secondary AML and RAEB-T.
  • CAG as the induction therapy seems promising for the treatment of various categories of poor-prognosis AML.
  • [MeSH-major] Anemia, Refractory, with Excess of Blasts / drug therapy. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cytarabine / administration & dosage. Leukemia, Myeloid, Acute / drug therapy
  • [MeSH-minor] Aclarubicin / administration & dosage. Aclarubicin / toxicity. Disease-Free Survival. Female. Follow-Up Studies. Granulocyte Colony-Stimulating Factor / administration & dosage. Granulocyte Colony-Stimulating Factor / toxicity. Humans. Lymphocyte Activation. Male. Neoplasms, Second Primary / drug therapy. Survival Rate. Treatment Outcome

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  • (PMID = 10846828.001).
  • [ISSN] 0925-5710
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] IRELAND
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 74KXF8I502 / Aclarubicin; CAG protocol
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10. Fukuhara T, Miyake T, Maekawa I, Kurosawa M, Suzuki S, Noto S, Mori A, Chiba K, Toyoshima T, Hirano T, Morioka M, Tsutsumi Y, Okabe M, Kakinoki Y: Treatment with low-dose cytosine arabinoside followed by administration of macrophage colony-stimulating factor prolongs the survival of patients with RAEB, RAEB-T, or leukemic phase myelodysplastic syndrome: a pilot study. Int J Hematol; 2000 Jun;71(4):366-71
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  • [Title] Treatment with low-dose cytosine arabinoside followed by administration of macrophage colony-stimulating factor prolongs the survival of patients with RAEB, RAEB-T, or leukemic phase myelodysplastic syndrome: a pilot study.
  • The treatment of patients with aggressive subclasses of myelodysplastic syndrome (MDS) remains a challenge.
  • In an effort to improve the survival of patients with refractory anemia with excess blasts (RAEB), RAEB in transformation (RAEB-t), or acute myelogenous leukemia transformed from MDS (MDS-AML), we conducted a small trial in which 28 such patients were treated with low-dose cytosine arabinoside (LDAraC) followed by administration of macrophage colony-stimulating factor (M-CSF).
  • The overall rate of response to the treatment was 61%, including 39% with a complete response, which is higher than rates obtained in previous studies in which LDAraC alone was administered to patients with MDS.
  • Median survival was 23.5 months in cases of RAEB, 16.7 months in cases of RAEB-t, and 19.7 months in cases of MDS-AML.
  • It is suggested that M-CSF added to the administration of LDAraC plays an active role in the therapy.
  • No therapy-related death occurred.
  • It is concluded that therapy with LDAraC + M-CSF is a useful treatment option for patients with aggressive subclasses of MDS and MDS-AML to provide better response and survival.
  • [MeSH-major] Anemia, Refractory, with Excess of Blasts / drug therapy. Cytarabine / administration & dosage. Macrophage Colony-Stimulating Factor / administration & dosage. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Adult. Aged. Female. Humans. Leukemia, Myeloid, Acute / drug therapy. Leukemia, Myeloid, Acute / etiology. Male. Middle Aged. Pilot Projects. Survival Rate. Treatment Outcome

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  • (PMID = 10905057.001).
  • [ISSN] 0925-5710
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Case Reports; Clinical Trial; Comparative Study; Journal Article
  • [Publication-country] IRELAND
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 81627-83-0 / Macrophage Colony-Stimulating Factor
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11. Jackson G, Taylor P, Smith GM, Marcus R, Smith A, Chu P, Littlewood TJ, Duncombe A, Hutchinson M, Mehta AB, Johnson SA, Carey P, MacKie MJ, Ganly PS, Turner GE, Deane M, Schey S, Brookes J, Tollerfield SM, Wilson MP: A multicentre, open, non-comparative phase II study of a combination of fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor in relapsed and refractory acute myeloid leukaemia and de novo refractory anaemia with excess of blasts in transformation. Br J Haematol; 2001 Jan;112(1):127-37
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  • [Title] A multicentre, open, non-comparative phase II study of a combination of fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor in relapsed and refractory acute myeloid leukaemia and de novo refractory anaemia with excess of blasts in transformation.
  • The primary objective of this study was to determine the complete remission (CR) rate achieved with the FLAG (fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor) regimen in patients with relapsed or refractory acute myeloid leukaemia (AML) or de novo refractory anaemia with excess of blasts in transformation (RAEB-t).
  • Induction treatment consisted of between one and two courses of FLAG.
  • Patients achieving CR received between one and two courses of consolidation treatment.
  • CR rates were: 17 out of 21 (81%) in late relapse AML (Group 1), 13 out of 44 (30%) in early relapse/refractory AML (Group 2), and 10 out of 18 (56%) in de novo RAEB-t (Group 3).
  • Median survival times were 1.4 years, 3 months and 1.6 years in Groups 1, 2 and 3 respectively.
  • The FLAG regimen offers a very effective alternative treatment for CR induction in poor prognosis adult patients with either relapsed or refractory AML or de novo RAEB-t.
  • FLAG delivers high-dose treatment without increasing overall toxicity, an approach which is of particular value in older patients, who constitute the majority in these diseases.
  • It is therefore an important advance in developing new treatment options for these patients.
  • [MeSH-major] Anemia, Refractory, with Excess of Blasts / drug therapy. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid / drug therapy

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  • (PMID = 11167793.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article; Multicenter Study
  • [Publication-country] England
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; FA2DM6879K / Vidarabine; FLAG protocol
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12. Hofmann WK, Heil G, Zander C, Wiebe S, Ottmann OG, Bergmann L, Hoeffken K, Fischer JT, Knuth A, Kolbe K, Schmoll HJ, Langer W, Westerhausen M, Koelbel CB, Hoelzer D, Ganser A: Intensive chemotherapy with idarubicin, cytarabine, etoposide, and G-CSF priming in patients with advanced myelodysplastic syndrome and high-risk acute myeloid leukemia. Ann Hematol; 2004 Aug;83(8):498-503
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  • [Title] Intensive chemotherapy with idarubicin, cytarabine, etoposide, and G-CSF priming in patients with advanced myelodysplastic syndrome and high-risk acute myeloid leukemia.
  • In an attempt to improve the complete remission (CR) rates and to prolong the remission duration especially in elderly patients > 50 years of age, we have used a combination chemotherapy of idarubicin (10 mg/m2 IV x 3 days), cytarabine (AraC, 100 mg/m2 CIVI x 7d), and etoposide (100 mg/m2 x 5 days) in combination with granulocyte colony-stimulating factor (G-CSF) priming [5 mg/kg SQ day 1 until absolute neutrophil count (ANC) recovery] for remission induction.
  • A total of 112 patients (57 male/55 female) with a median age of 58 years (range: 22-75) have been entered and are evaluable for response: 19 refractory anemia with excess of blast cells in transformation (RAEB-T), 84 acute myeloid leukemia (AML) evolving from myelodysplastic syndrome (MDS), and 9 secondary AML after chemotherapy/radiotherapy.
  • The overall CR rate was 62%, partial remission (PR) rate 10%, treatment failure 16%, and early death rate 12%.
  • Compared to our previous trial (AML-MDS Study 01-92) which was done with identical chemotherapy but no G-CSF priming in 110 patients with RAEB-T, AML after MDS, or secondary AML (identical median age, age range, and distribution of subtypes), the CR rate in all patients, as well as CR rate, overall survival, and relapse-free survival in patients > 60 years have significantly been improved.
  • Thus, intensive chemotherapy with G-CSF priming is both well tolerated and highly effective for remission induction in these high-risk patients.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Granulocyte Colony-Stimulating Factor / administration & dosage. Myelodysplastic Syndromes / drug therapy. Myelodysplastic Syndromes / mortality
  • [MeSH-minor] Acute Disease. Adult. Aged. Amsacrine / administration & dosage. Anemia, Refractory, with Excess of Blasts / drug therapy. Anemia, Refractory, with Excess of Blasts / mortality. Cytarabine / administration & dosage. Etoposide / administration & dosage. Female. Humans. Idarubicin / administration & dosage. Leukemia, Myeloid / drug therapy. Leukemia, Myeloid / mortality. Male. Middle Aged. Remission Induction / methods. Risk. Survival Rate. Treatment Outcome

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  • [Copyright] Copyright 2004 Springer-Verlag
  • (PMID = 15156346.001).
  • [ISSN] 0939-5555
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 00DPD30SOY / Amsacrine; 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 6PLQ3CP4P3 / Etoposide; ZRP63D75JW / Idarubicin
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13. Beran M, Shen Y, Kantarjian H, O'Brien S, Koller CA, Giles FJ, Cortes J, Thomas DA, Faderl S, Despa S, Estey EH: High-dose chemotherapy in high-risk myelodysplastic syndrome: covariate-adjusted comparison of five regimens. Cancer; 2001 Oct 15;92(8):1999-2015
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  • [Title] High-dose chemotherapy in high-risk myelodysplastic syndrome: covariate-adjusted comparison of five regimens.
  • BACKGROUND: Antileukemic chemotherapy has been used for two decades to treat high-risk myelodysplastic syndrome (refractory anemia with excess of blasts [RAEB] and RAEB in transformation into acute leukemia [RAEB-t]) patients.
  • In the absence of randomized trials, the relative merits of various treatment regimens are unknown.
  • In addition to defining the role of high-intensity chemotherapy in the overall outcome for patients with RAEB-t and RAEB, the authors determined the relative merits of the five regimens (IA, FA, FAI, TA, and CAT), accounting for the nonrandom distribution of the prognostic covariates.
  • RESULTS: The overall complete response (CR) rate of 58% was significantly associated with karyotype, performance status (PS), treatment in the laminar air flow room, duration of antecedent hematologic disorder and age, but not French-American-British or International Prognostic Scoring System risk categories.
  • The trend for time to death was the same as for time to recurrence in all groups.
  • Multivariate analysis of time to death identified treatment regimen (FA, FAI, and CAT), cytogenetic status (-5/-7), increasing age, and PS greater than 2 as significant independent unfavorable prognostic factors.
  • After prognostic variables were accounted for, survival with IA treatment remained superior to that of FA and FAI but comparable to TA, and CR duration was only marginally shorter with FA.
  • CONCLUSIONS: Although the newer regimens did not improve outcome, TA and CAT produced results comparable to those of IA and may be considered treatment alternatives.
  • The TA regimen was particularly effective in RAEB patients and could be delivered safely, with low induction mortality.
  • Our results indicated that although CR seemed associated with survival advantage, innovative post-remission managements represent a challenge because improvement in outcome is not likely to come from intensified therapy.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Myelodysplastic Syndromes / drug therapy. Vidarabine / analogs & derivatives

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  • [Copyright] Copyright 2001 American Cancer Society.
  • (PMID = 11596013.001).
  • [ISSN] 0008-543X
  • [Journal-full-title] Cancer
  • [ISO-abbreviation] Cancer
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 7M7YKX2N15 / Topotecan; 8N3DW7272P / Cyclophosphamide; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine; ZRP63D75JW / Idarubicin
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14. Hast R, Hellström-Lindberg E, Ohm L, Björkholm M, Celsing F, Dahl IM, Dybedal I, Gahrton G, Lindberg G, Lerner R, Linder O, Löfvenberg E, Nilsson-Ehle H, Paul C, Samuelsson J, Tangen JM, Tidefelt U, Turesson I, Wahlin A, Wallvik J, Winquist I, Oberg G, Bernell P: No benefit from adding GM-CSF to induction chemotherapy in transforming myelodysplastic syndromes: better outcome in patients with less proliferative disease. Leukemia; 2003 Sep;17(9):1827-33
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  • [Title] No benefit from adding GM-CSF to induction chemotherapy in transforming myelodysplastic syndromes: better outcome in patients with less proliferative disease.
  • In this prospective randomized multicenter trial 93 patients, median age 72 years, with RAEB-t (n=25) and myelodysplastic syndrome (MDS)-AML (n=68) were allocated to a standard induction chemotherapy regimen (TAD 2+7) with or without addition of granulocyte-macrophage-CSF (GM-CSF).
  • Median survival times for all patients, CR patients, and non-CR patients were 280, 550, and 100 days, respectively, with no difference between the arms.
  • Thus, addition of GM-CSF to chemotherapy showed no clinical benefit in terms of response but carried an increased risk for side effects.
  • We present a clinically useful tool to predict response to chemotherapy and survival in elderly patients with transforming MDS, favoring patients with features of less proliferative disease.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cytarabine / therapeutic use. Daunorubicin / therapeutic use. Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use. Leukemia, Myeloid / drug therapy. Thioguanine / therapeutic use
  • [MeSH-minor] Acute Disease. Adult. Aged. Aged, 80 and over. Anemia, Refractory, with Excess of Blasts / drug therapy. Anemia, Refractory, with Excess of Blasts / pathology. Cell Transformation, Neoplastic. Female. Follow-Up Studies. Humans. Male. Middle Aged. Myelodysplastic Syndromes / drug therapy. Myelodysplastic Syndromes / pathology. Prospective Studies. Remission Induction. Survival Rate

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  • (PMID = 12970783.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Clinical Trial; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 83869-56-1 / Granulocyte-Macrophage Colony-Stimulating Factor; FTK8U1GZNX / Thioguanine; ZS7284E0ZP / Daunorubicin; DAT protocol 1
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15. Ganser A, Heil G, Seipelt G, Hofmann W, Fischer JT, Langer W, Brockhaus W, Kolbe K, Ittel TH, Brack N, Fuhr HG, Knuth P, Höffken K, Bergmann L, Hoelzer D: Intensive chemotherapy with idarubicin, ara-C, etoposide, and m-AMSA followed by immunotherapy with interleukin-2 for myelodysplastic syndromes and high-risk Acute Myeloid Leukemia (AML). Ann Hematol; 2000 Jan;79(1):30-5
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  • [Title] Intensive chemotherapy with idarubicin, ara-C, etoposide, and m-AMSA followed by immunotherapy with interleukin-2 for myelodysplastic syndromes and high-risk Acute Myeloid Leukemia (AML).
  • Intensive chemotherapy followed by treatment with interleukin-2 (IL-2) was evaluated in a prospective, randomized, multicenter trial including 18 patients with refractory anemia with excess of blasts in transformation (RAEB-T), 86 patients with acute myeloid leukemia (AML) evolving from myelodysplastic syndromes, and six patients with secondary AML after previous chemotherapy.
  • Median duration of survival and relapse-free survival were not statistically different in the two IL-2 treatment arms.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Immunotherapy. Interleukin-2 / therapeutic use. Leukemia, Myeloid / drug therapy. Myelodysplastic Syndromes / drug therapy. Myelodysplastic Syndromes / therapy
  • [MeSH-minor] Acute Disease. Adolescent. Adult. Aged. Cytarabine / administration & dosage. Dose-Response Relationship, Drug. Etoposide / administration & dosage. Female. Humans. Idarubicin / administration & dosage. Male. Middle Aged. Prospective Studies. Survival Rate


16. Hofmann WK, Seipelt G, Ottmann OG, Kalina U, Koschmieder S, Brücher J, Frickhofen N, Klausmann M, Mitrou PS, Hoelzer D: Effect of treatment with amifostine used as a single agent in patients with refractory anemia on clinical outcome and serum tumor necrosis factor alpha levels. Ann Hematol; 2000 May;79(5):255-8
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  • [Title] Effect of treatment with amifostine used as a single agent in patients with refractory anemia on clinical outcome and serum tumor necrosis factor alpha levels.
  • In these studies, patients with refractory anemia (RA), RA with excess of blasts (RAEB), and RAEB in transformation (RAEB-T) were analyzed together, resulting in response rates varying from 8% to 30%.
  • The present multi-center study evaluated whether treatment with amifostine is of clinical benefit in patients with RA who are transfusion dependent.
  • Four treatment cycles were planned, each consisting of intravenous amifostine at 200 mg/m2/day three times per week followed by a 2-week interval.
  • Since tumor necrosis factor (TNF) alpha is a main suppressive cytokine for hematopoiesis in RA patients, serum samples for analyzing endogenous levels of TNF alpha were collected prior to the study and after four treatment cycles.
  • In one patient, disease progression from RA to RAEB was observed.
  • Serum TNF alpha levels were increased in MDS patients compared with normal controls (18.8 pg/ml vs 9.1 pg/ml), and there was no change during the treatment with amifostine (17.5 pg/ml).
  • In conclusion, treatment with amifostine as a single agent was of limited benefit in patients with RA.
  • The serum TNF alpha levels were unchanged during treatment with amifostine in RA patients.
  • [MeSH-major] Amifostine / therapeutic use. Anemia, Refractory / blood. Anemia, Refractory / drug therapy. Tumor Necrosis Factor-alpha / metabolism
  • [MeSH-minor] Aged. Anemia, Refractory, with Excess of Blasts / drug therapy. Drug Administration Schedule. Female. Humans. Injections, Intravenous. Male. Middle Aged. Nausea / chemically induced. Treatment Outcome. Venous Thrombosis / chemically induced

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  • (PMID = 10870480.001).
  • [ISSN] 0939-5555
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] GERMANY
  • [Chemical-registry-number] 0 / Tumor Necrosis Factor-alpha; M487QF2F4V / Amifostine
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17. Nakai K, Kanda Y, Fukuhara S, Sakamaki H, Okamoto S, Kodera Y, Tanosaki R, Takahashi S, Matsushima T, Atsuta Y, Hamajima N, Kasai M, Kato S: Value of chemotherapy before allogeneic hematopoietic stem cell transplantation from an HLA-identical sibling donor for myelodysplastic syndrome. Leukemia; 2005 Mar;19(3):396-401
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  • [Title] Value of chemotherapy before allogeneic hematopoietic stem cell transplantation from an HLA-identical sibling donor for myelodysplastic syndrome.
  • Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a curative treatment for myelodysplastic syndrome (MDS).
  • The object of this study was to evaluate the impact of chemotherapy before allo-SCT.
  • Multivariate analyses identified karyotype, FAB classification, and the history of chemotherapy before allo-SCT as significant predictors for OS.
  • OS at 5 years was 57% for patients who underwent allo-SCT as a primary treatment for refractory anemia with excess blasts in transformation (RAEB-t) or secondary acute myeloid leukemia (AML) and 54% for those who underwent allo-SCT in remission after induction chemotherapy (P=0.81).
  • Although only a randomized controlled trial will be able to establish a definite conclusion, these results do not support the administration of induction chemotherapy for patients with RAEB-t or secondary AML before allo-SCT.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Hematopoietic Stem Cell Transplantation. Histocompatibility Testing. Myelodysplastic Syndromes / therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Female. Graft vs Host Disease / mortality. Graft vs Host Disease / prevention & control. Graft vs Host Disease / therapy. Histocompatibility. Humans. Male. Middle Aged. Recurrence. Retrospective Studies. Siblings. Survival Analysis. Transplantation Conditioning. Transplantation, Homologous


18. Shi J, Shao ZH, Liu H, Bai J, Cao YR, He GS, Tu MF, Wang XL, Hao YS, Yang TY, Yang CL: Transformation of myelodysplastic syndromes into acute myeloid leukemias. Chin Med J (Engl); 2004 Jul;117(7):963-7
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  • [Title] Transformation of myelodysplastic syndromes into acute myeloid leukemias.
  • We studied the transformation of MDS into acute myeloid leukemia (AML).
  • METHODS: Leukemic transformation in 151 patients with MDS was dynamically followed up.
  • The clinical manifestation, peripheral blood and bone marrow condition, karyotypes, immunophenotypes, response to treatment, and prognosis of AML evolution from MDS (MDS-AML) were also observed.
  • There were no significant differences between rates of leukemic transformation in comparison with the refractory anemia (RA), RA with excess of blasts (RAEB), and RAEB in transformation (RAEB-t) patient groups.
  • Transformation occurred either gradually or rapidly.
  • There were five parameters positively correlated to leukemic transformation: under 40 years of age, pancytopenia of 3 lineages, more than 15% blasts in the bone marrow, at least two abnormal karyotypes, and treatment with combined chemotherapy.
  • Two (9.52%) MDS-AML patients developed extramedullary infiltration.
  • After developing AML, 8 (47.06%) patients developed abnormal karyotypes.
  • High expression of immature myeloid antigens, including CD33 [(49.83 +/- 24.50)%], CD13 [(36.38 +/- 33.84)%], monocytic antigen CD14 [(38.50 +/- 24.60)%], and stem cell marker CD34 [(34.67 +/- 30.59)%], were found on bone marrow mononuclear cells from MDS-AML patients after leukemic transformation.
  • A low complete remission rate (31.25%) and a short survival time, with median survival of 6 (1 - 28) months, were found in patients with MDS-AML treated by induction chemotherapy.


19. Fulciniti F, Zeppa P, Marino G, Martinelli V, Ciancia R, Del Vecchio L, Rotoli B, Palombini L: Lymphnode localization of extramedullary myeloid cell tumor in myelodysplastic syndrome: report of one case diagnosed by fine-needle cytology. Diagn Cytopathol; 2003 Mar;28(3):136-9
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  • Trilineage extramedullary myeloid tumor (EMT) is an uncommon medical condition mostly diagnosed in patients affected by acute or chronic myeloid leukemia or, more rarely, by a myelodysplastic syndrome, among which the most frequent is refractory anemia with excess of blasts in transformation (RAEB-t).
  • A 70-year-old lady with previous history of intestinal resection for colonic adenocarcinoma in 1995 and subsequently treated with 5-fuorouracyl developed a refractory anemia with excess of blasts (RAEB) in 1998.
  • During the follow-up, a progression to RAEB-t was recorded.
  • During chemotherapy for this condition, slight enlargement of left supraclavicular and right submandibular nodes was noticed.
  • The patient was treated with low doses of chemotherapy with a good response lasting 12 months.
  • Furthermore, the extramedullary myeloid tumor in this case did not significantly affect the response to the chemotherapy of RAEB-t.
  • [MeSH-major] Anemia, Refractory, with Excess of Blasts / pathology. Biopsy, Needle / methods. Leukemia, Myeloid / pathology. Lymph Nodes / pathology. Soft Tissue Neoplasms / pathology
  • [MeSH-minor] Aged. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Female. Flow Cytometry. Humans. Neoplasms, Second Primary. Treatment Outcome

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  • [Copyright] Copyright 2003 Wiley-Liss, Inc.
  • (PMID = 12619094.001).
  • [ISSN] 8755-1039
  • [Journal-full-title] Diagnostic cytopathology
  • [ISO-abbreviation] Diagn. Cytopathol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
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20. Perez A, Kennedy C, Standen G, Oxley J: A case of monocytic leukaemia cutis in a patient with myelodysplastic syndrome transforming to acute myeloid leukaemia. Clin Exp Dermatol; 2004 Sep;29(5):497-8
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  • Subsequently, she developed pancytopaenia and a bone marrow biopsy revealed refractory anaemia with excess blasts in transformation (RAEB-T) with a high monoblastic component.
  • When occurring with a myelodysplastic syndrome, leukaemia cutis often heralds malignant transformation to acute myeloid leukaemia.
  • Prompt diagnosis in this situation may identify a group of high-risk patients with myelodysplastic syndrome for whom chemotherapy and allogenic bone marrow transplantation, rather than the more conventional approach of supportive treatment, could be a more appropriate management strategy.
  • [MeSH-major] Anemia, Refractory, with Excess of Blasts / pathology. Leukemia / pathology. Leukemia, Myeloid, Acute / pathology
  • [MeSH-minor] Bone Marrow Transplantation / methods. Cell Transformation, Neoplastic. Fatal Outcome. Female. Humans. Middle Aged


21. Voulgari PV, Hatzimichael EC, Tsiara S, Tzallas C, Drosos AA, Bourantas KL: Investigation for the presence of anti-erythropoietin antibodies in patients with myelodysplastic syndromes. Eur J Haematol; 2001 Jan;66(1):31-6
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  • OBJECTIVES: Recombinant human erythropoietin (rHuEpo) improves anemia in 25% of patients with myelodysplastic syndromes (MDS).
  • The variable and sometimes low response rate to rHuEpo treatment raises the question whether the existence of autoantibodies against erythropoietin (epo) is partially responsible.
  • Sixteen patients had refractory anemia (RA), 13 had RA with ringed sideroblasts, 3 had RA with excess of blasts (RAEB), 9 had RAEB in transformation and 2 patients had chronic myelomonocytic leukemia.
  • They were divided in 3 groups according to rHuEpo treatment.
  • Group A consisted of 10 patients who did not receive rHuEpo treatment.
  • Group B included 13 patients who were on rHuEpo treatment (150 IU/kg subcutaneously, 3 times weekly) showing an increase of hemoglobin (Hb) values or reduction of transfusion requirements and Group C consisted of 20 patients who did not respond or stopped responding to rHuEpo treatment.
  • CONCLUSION: We suggest that anti-epo autoantibodies do not contribute to the development of MDS-related anemia and are not responsible for the modest response to rHuEpo treatment.
  • Further investigation is needed to identify possible reasons for the low response rate to rHuEpo treatment.
  • [MeSH-minor] Aged. Aged, 80 and over. Anemia, Refractory / blood. Anemia, Refractory / drug therapy. Anemia, Refractory / immunology. Anemia, Refractory / therapy. Anemia, Refractory, with Excess of Blasts / blood. Anemia, Refractory, with Excess of Blasts / drug therapy. Anemia, Refractory, with Excess of Blasts / immunology. Anemia, Refractory, with Excess of Blasts / therapy. Antibody Specificity. Blood Cell Count. Blood Transfusion. Combined Modality Therapy. Female. Hemoglobins / analysis. Humans. Leukemia, Myelomonocytic, Chronic / blood. Leukemia, Myelomonocytic, Chronic / drug therapy. Leukemia, Myelomonocytic, Chronic / immunology. Leukemia, Myelomonocytic, Chronic / therapy. Male. Middle Aged. Recombinant Proteins / immunology. Recombinant Proteins / therapeutic use. Treatment Failure

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  • [CommentIn] Eur J Haematol. 2002 Sep;69(3):189-90 [12406016.001]
  • (PMID = 11168505.001).
  • [ISSN] 0902-4441
  • [Journal-full-title] European journal of haematology
  • [ISO-abbreviation] Eur. J. Haematol.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] Denmark
  • [Chemical-registry-number] 0 / Autoantibodies; 0 / Autoantigens; 0 / Hemoglobins; 0 / Isoantibodies; 0 / Isoantigens; 0 / Recombinant Proteins; 11096-26-7 / Erythropoietin
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22. Raza A, Lisak L, Billmeier J, Pervaiz H, Mumtaz M, Gohar S, Wahid K, Galili N: Phase II study of topotecan and thalidomide in patients with high-risk myelodysplastic syndromes. Leuk Lymphoma; 2006 Mar;47(3):433-40
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  • This phase II trial investigated the safety and preliminary efficacy of a topotecan/thalidomide combination therapy in patients with myelodysplastic syndrome who had refractory anemia with excess blasts (RAEB), RAEB with transformation, or chronic myelomonocytic anemia.
  • Therapy was generally well tolerated compared to high-dose chemotherapy.
  • Three patients died from disease progression/infections during topotecan therapy, and four patients discontinued topotecan because of high-grade neutropenia (two patients), syncope (one patient), or hip surgery (one patient).
  • Of 24 patients who received thalidomide, three discontinued because of treatment-related toxicity.
  • Approximately one-third of the patients had decreases in bone marrow blasts of 50%.
  • Therefore, a topotecan and thalidomide combination therapy is promising, although further studies are needed to determine the optimum doses and schedule.
  • [MeSH-major] Myelodysplastic Syndromes / drug therapy. Thalidomide / therapeutic use. Topotecan / therapeutic use
  • [MeSH-minor] Aged. Anemia, Refractory, with Excess of Blasts / drug therapy. Anemia, Refractory, with Excess of Blasts / pathology. Dose-Response Relationship, Drug. Drug Administration Schedule. Drug Therapy, Combination. Drug Tolerance. Female. Humans. Male. Middle Aged. Risk Factors. Time Factors. Treatment Outcome

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  • (PMID = 16396766.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 4Z8R6ORS6L / Thalidomide; 7M7YKX2N15 / Topotecan
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23. Guan M, Chen SC, Li RS, Ge CW, Zhu HL: [Low dose all-trans retinoic acid and androgen therapy for patients with myelodysplastic syndrome]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2004 Dec;12(6):774-8
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  • [Title] [Low dose all-trans retinoic acid and androgen therapy for patients with myelodysplastic syndrome].
  • To explore therapeutic efficacy of androgens and low dose all-trans retinoic acid (ATRA) for myelodysplastic syndrome (MDS) patients, 55 patients of MDS were observed, including 41 cases of refractory anemia (RA), 11 cases of refractory anemia with excess of blasts (RAEB), 2 cases of refractory anemia with excess of blasts in transformation (RAEB-t) and 1 case of chronic myeloic-monocytic leukemia (CMML).
  • In conclusion, danazol or stanazol in combination with low dose ATRA are partialy effective in therapy for patients with low-risk myelodysplastic syndrome.

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  • (PMID = 15631659.001).
  • [ISSN] 1009-2137
  • [Journal-full-title] Zhongguo shi yan xue ye xue za zhi
  • [ISO-abbreviation] Zhongguo Shi Yan Xue Ye Xue Za Zhi
  • [Language] CHI
  • [Publication-type] English Abstract; Journal Article; Randomized Controlled Trial
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Androgens; 0 / Antineoplastic Agents; 5688UTC01R / Tretinoin
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24. Pawson R, Potter MN, Theocharous P, Lawler M, Garg M, Yin JA, Rezvani K, Craddock C, Rassam S, Prentice HG: Treatment of relapse after allogeneic bone marrow transplantation with reduced intensity conditioning (FLAG +/- Ida) and second allogeneic stem cell transplant. Br J Haematol; 2001 Dec;115(3):622-9
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  • [Title] Treatment of relapse after allogeneic bone marrow transplantation with reduced intensity conditioning (FLAG +/- Ida) and second allogeneic stem cell transplant.
  • Fludarabine-containing 'non-myeloablative' chemotherapy followed by further allo SCT may offer more rapid and effective disease control.
  • We report 14 patients with relapse after allo SCT for acute leukaemia [seven acute myeloid leukaemia (AML), five acute lymphoblastic leukaemia (ALL)] or refractory anaemia with excess blasts in transformation (RAEB-t, n = 2) treated with fludarabine, high-dose cytosine arabinoside (ara-C) and granulocyte colony-simulating factor (G-CSF) with (n = 10) or without (n = 2) idarubicin (FLAG +/- Ida) or DaunoXome (FLAG-X) (n = 2) and second allo SCT from the original donor.
  • Transplants were well tolerated with no treatment-related deaths.
  • FLAG +/- Ida and second allo SCT is a safe and useful approach and may be more effective than DLI in the treatment of acute leukaemias relapsing after conventional allo SCT.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Bone Marrow Transplantation. Cytarabine / administration & dosage. Granulocyte Colony-Stimulating Factor / administration & dosage. Idarubicin / administration & dosage. Leukemia / therapy. Transplantation Conditioning / methods. Vidarabine / administration & dosage. Vidarabine / analogs & derivatives
  • [MeSH-minor] Acute Disease. Adult. Anemia, Refractory, with Excess of Blasts / therapy. Child. Child, Preschool. Disease-Free Survival. Female. Filgrastim. Graft vs Host Disease / immunology. Graft vs Host Disease / prevention & control. Humans. Leukemia, Myeloid / therapy. Male. Middle Aged. Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy. Recombinant Proteins. Recurrence. Reoperation. Retrospective Studies. Survival Rate. Transplantation, Homologous

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  • (PMID = 11736947.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Recombinant Proteins; 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; FA2DM6879K / Vidarabine; PVI5M0M1GW / Filgrastim; ZRP63D75JW / Idarubicin; Ida-FLAG protocol
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25. Sato N, Nakazato T, Kizaki M, Ikeda Y, Okamoto S: Transformation of myelodysplastic syndrome to acute lymphoblastic leukemia: a case report and review of the literature. Int J Hematol; 2004 Feb;79(2):147-51
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  • [Title] Transformation of myelodysplastic syndrome to acute lymphoblastic leukemia: a case report and review of the literature.
  • However, the transformation of MDS into acute lymphoblastic leukemia (ALL) is extremely rare.
  • We present a case of refractory anemia with excess of blasts (RAEB) that transformed into ALL.
  • MDS (RAEB) was diagnosed in a 68-year-old Japanese woman in August 2001.
  • Two months later, MDS progressed to erythroleukemia (French-American-British [FAB]classification, acute myeloid leukemia [AML]-M6), and in December, 2001, she was treated with combined chemotherapy containing aclarubicin, cytarabine, and granulocyte colony-stimulating factor, which improved her clinical symptoms.
  • However, 1 month after the chemotherapy, she developed ALL.
  • The blasts at that time had a markedly basophilic cytoplasm with multiple cytoplasmic vacuoles, and their morphology mimicked that of ALL-L3.
  • The blasts also expressed CD13, a myeloid marker, in addition to lymphoid markers.
  • The patient was treated with chemotherapy, but she developed tumor lysis syndrome and died of multiple organ failure.
  • Although the precise mechanism of lymphoid transformation is not yet fully understood, this case clinically supports the nature of MDS as a pluripotent hematopoietic stem cell disorder.
  • [MeSH-major] Cell Transformation, Neoplastic / pathology. Myelodysplastic Syndromes / pathology. Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology


26. Terpos E, Mougiou A, Kouraklis A, Chatzivassili A, Michalis E, Giannakoulas N, Manioudaki E, Lazaridou A, Bakaloudi V, Protopappa M, Liapi D, Grouzi E, Parharidou A, Symeonidis A, Kokkini G, Laoutaris NP, Vaipoulos G, Anagnostopoulos NI, Christakis JI, Meletis J, Bourantas KL, Zoumbos NC, Yataganas X, Viniou NA, Greek MDS Study Group: Prolonged administration of erythropoietin increases erythroid response rate in myelodysplastic syndromes: a phase II trial in 281 patients. Br J Haematol; 2002 Jul;118(1):174-80
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  • Treatment with recombinant human erythropoietin (rHuEpo) improves anaemia in approximately 20% of patients with myelodysplastic syndromes (MDS).
  • We investigated the potential advantage of a prolonged administration of rHuEpo to achieve higher erythroid response rates (RR) in 281 MDS patients: 118 with refractory anaemia (RA), 77 with refractory anaemia and ringed sideroblasts (RARS), 59 with refractory anaemia with excess of blasts and blast count < 10% (RAEB-I), and 27 with RAEB and blast count between 11-20% (RAEB-II).
  • Response to treatment was evaluated after 12 and 26 weeks of therapy.
  • The overall RR was 45.1%; the RR for RA, RARS, RAEB-I and RAEB-II were 48.3%, 58.4%, 33.8% and 13% respectively.
  • A significant increase in RR was observed at week 26 in RA, RARS and RAEB-I patients, as the response probability increased with treatment duration.
  • The median duration of response was 68 weeks and the overall risk of leukaemic transformation was 21.7%.
  • [MeSH-major] Erythropoietin / therapeutic use. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Aged. Aged, 80 and over. Anemia, Refractory / drug therapy. Anemia, Refractory, with Excess of Blasts / drug therapy. Anemia, Sideroblastic / drug therapy. Female. Humans. Male. Middle Aged. Prospective Studies. Treatment Outcome


27. Parikh SH, Mendizabal A, Martin PL, Prasad VK, Szabolcs P, Driscoll TA, Kurtzberg J: Unrelated donor umbilical cord blood transplantation in pediatric myelodysplastic syndrome: a single-center experience. Biol Blood Marrow Transplant; 2009 Aug;15(8):948-55
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  • Myelodysplastic syndromes (MDS) respond poorly to chemotherapy.
  • The median age was 11.1 years (range: 1.1-19.7), median weight was 38.6 kg (range: 9.6-62.6), 61% of patients were male, and median time from diagnosis to transplant was 6.6 months (range: 2.0-61.4).
  • MDS stage was refractory anemia (RA) in 12, refractory anemia with excess blasts (RAEB) in 8, and refractory anemia with excess blasts in transformation (RAEB-T) in 3 patients; 18 (78%) patients had primary MDS.
  • Three patients developed acute GVHD (aGVHD) grades II-IV with a cumulative incidence at 100 days of 13% (95% CI 0.0%-27.1.0%).
  • [MeSH-major] Cord Blood Stem Cell Transplantation / methods. Myelodysplastic Syndromes / therapy
  • [MeSH-minor] Adolescent. Adult. Anemia, Refractory, with Excess of Blasts. Chemoprevention / methods. Child. Female. Graft vs Host Disease / drug therapy. Graft vs Host Disease / prevention & control. Humans. Male. Middle Aged. Retrospective Studies. Survival Analysis. Tissue Donors. Treatment Outcome. Whole-Body Irradiation. Young Adult


28. Strupp C, Germing U, Aivado M, Misgeld E, Haas R, Gattermann N: Thalidomide for the treatment of patients with myelodysplastic syndromes. Leukemia; 2002 Jan;16(1):1-6
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  • [Title] Thalidomide for the treatment of patients with myelodysplastic syndromes.
  • We examined the efficacy of thalidomide in 34 patients with myelodysplastic syndromes (MDS): five RAEB-T, four RAEB, three CMML, six RARS, and 16 RA.
  • In the remaining 29 patients (median follow-up: 13 months), treatment responses were classified according to the IWG criteria.
  • Six patients (four RA, two CMML) showed progressive disease (five with transformation into AML) and four patients showed stable disease.
  • Nine of the responders (three RA, one RARS, two RAEB, three RAEB-T) achieved partial remission with granulocytes > or = 1500/microl, Hb > 11 g/dl and platelets > or =100,000/microl.
  • Four patients (one RARS, one CMML, one RAEB, one RAEB-T) had a major response, with platelet and RBC transfusion independence.
  • Hematological improvement occurred after a median of 2 months of thalidomide treatment.
  • Two patients (RAEB-T) relapsed after a partial remission lasting 8 and 16 months, respectively.
  • In summary, a therapeutic benefit was achieved in 19 of 34 study patients (56%).
  • [MeSH-major] Myelodysplastic Syndromes / drug therapy. Thalidomide / therapeutic use
  • [MeSH-minor] Aged. Aged, 80 and over. Anemia, Refractory / blood. Anemia, Refractory / drug therapy. Anemia, Refractory / therapy. Anemia, Refractory, with Excess of Blasts / blood. Anemia, Refractory, with Excess of Blasts / drug therapy. Anemia, Refractory, with Excess of Blasts / therapy. Blood Transfusion. Combined Modality Therapy. Constipation / chemically induced. Drug Evaluation. Fatigue / chemically induced. Female. Humans. Leukemia, Myelomonocytic, Chronic / blood. Leukemia, Myelomonocytic, Chronic / drug therapy. Leukemia, Myelomonocytic, Chronic / therapy. Male. Middle Aged. Peripheral Nervous System Diseases / chemically induced. Pilot Projects. Remission Induction. Treatment Outcome. Venous Thrombosis / chemically induced


29. Yilmaz A, Kaufmann CC, Binder C, Wörmann B, Haase D: Effects of amifostine in a patient with an advanced-stage myelodysplastic syndrome. Ann Hematol; 2001 Jan;80(1):53-7
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  • We report on a 63-year-old man with myelodysplastic syndrome at the stage of a refractory anemia with an excess of blasts in transformation (MDS-RAEB-T), first diagnosed in December 1996.
  • Two courses of chemotherapy were given, resulting in prolonged pancytopenia; however, no clearance of bone marrow (BM) blasts was achieved.
  • At that time, severe infections and daily epistaxis occurred.
  • After 2 months of persisting severe pancytopenia, we started a therapy with amifostine: 4 x 250 mg intravenously (i.v.) weekly for 1 month, followed by a maintenance therapy with 500 mg once weekly.
  • After 2 weeks of amifostine therapy, hematopoiesis began to improve.
  • In the subsequent 2 months, the patient became completely independent of the platelet transfusions; the transfusion frequency of RBC was permanently reduced (2 RBC transfusions/month) and a significant decrease of BM blasts was achieved.
  • After 30 weeks of amifostine therapy, the morphology of the MDS switched to a chronic myelomonocytic leukemia (CMML)-like appearance, with continuously increasing leukocytes, so that we discontinued amifostine therapy for 1 month to exclude a possible side effect of amifostine.
  • At that time, leukocytes further increased to 74,000/microl; thus, we decided to perform a cytoreductive chemotherapy (hydroxycarbamide) and continued weekly amifostine infusions.
  • During 1 year of amifostine therapy, the patient had a good quality of life, with no need for hospitalization and a complete cytogenetic remission.
  • Thus, amifostine might be a therapeutic option in older patients with advanced MDS.
  • [MeSH-major] Amifostine / therapeutic use. Myelodysplastic Syndromes / drug therapy. Radiation-Protective Agents / therapeutic use
  • [MeSH-minor] Apoptosis / drug effects. Humans. Male. Middle Aged

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  • (PMID = 11233778.001).
  • [ISSN] 0939-5555
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Radiation-Protective Agents; M487QF2F4V / Amifostine
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30. Kasper C, Zahner J, Sayer HG: Recombinant human erythropoietin in combined treatment with granulocyte- or granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes. J Cancer Res Clin Oncol; 2002 Sep;128(9):497-502
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  • [Title] Recombinant human erythropoietin in combined treatment with granulocyte- or granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes.
  • PURPOSE: Myelodysplastic syndromes (MDS) are a heterogeneous group of hemopoietic progenitor cell disorders, and patients with MDS regularly develop anemia and frequently become transfusion-dependent.
  • Treatment with erythropoietin (EPO) has been tried to correct anemia with only limited success with response rates ranging from 16% to 25%.
  • The average response rate for improving anemia was 41% in 207 patients treated with EPO and G-CSF, and 26% in 154 patients treated with EPO and GM-CSF.
  • There were higher response rates for refractory anemia (RA) (45%), ringed sideroblasts (RARS) (47%), and excess of blasts (RAEB) (38%) compared with blasts in transformation (RAEBT) (17%) for the treatment with EPO plus G-CSF.
  • The corresponding response rates for treatment with EPO plus GM-CSF were 30% (RA), 29% (RARS), 16% (RAEB), and 0% (RAEBT), respectively.
  • There seems to be a positive correlation between the duration of cytokine treatment and response rates, and higher response rates in early MDS stages compared to advanced entities.
  • However, controlled studies are mandatory to evaluate the role of the combined cytokine treatment in patients with MDS.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Erythropoietin / administration & dosage. Granulocyte Colony-Stimulating Factor / administration & dosage. Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Anemia / drug therapy. Humans. Interleukin-3 / administration & dosage. Recombinant Proteins

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  • (PMID = 12242514.001).
  • [ISSN] 0171-5216
  • [Journal-full-title] Journal of cancer research and clinical oncology
  • [ISO-abbreviation] J. Cancer Res. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Meta-Analysis
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Interleukin-3; 0 / Recombinant Proteins; 11096-26-7 / Erythropoietin; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 83869-56-1 / Granulocyte-Macrophage Colony-Stimulating Factor
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31. Yazji S, Giles FJ, Tsimberidou AM, Estey EH, Kantarjian HM, O'Brien SA, Kurzrock R: Antithymocyte globulin (ATG)-based therapy in patients with myelodysplastic syndromes. Leukemia; 2003 Nov;17(11):2101-6
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  • [Title] Antithymocyte globulin (ATG)-based therapy in patients with myelodysplastic syndromes.
  • The purpose of this study was to determine the efficacy of and tolerance to antithymocyte globulin (ATG)-based therapy in patients with myelodysplastic syndrome (MDS).
  • Therapy consisted of ATG 40 mg/kg/day daily intravenously (i.v.) for 4 days; cyclosporine daily orally for 6 months with levels titrated between 200 and 400 mg/dl; and methylprednisone 1 mg/kg i.v. daily before each dose of ATG.
  • A total of 18 patients had refractory anemia (RA) or RA with ringed sideroblasts (RARS), 10 patients had RA with excess blasts (RAEB), two patients had RAEB in transformation, and one patient had chronic myelomonocytic leukemia.
  • ATG, cyclosporine, and methylprednisone induced complete (N=4) or partial (N=1) remission in five patients (16% of total; RA, two patients; RARS, two patients; and RAEB, one patient).
  • [MeSH-major] Antilymphocyte Serum / therapeutic use. Immunosuppressive Agents / therapeutic use. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Adult. Aged. Blood Transfusion. Cyclosporine / therapeutic use. Female. Hematocrit. Humans. Karyotyping. Male. Methylprednisolone / therapeutic use. Middle Aged. Platelet Count. Treatment Outcome


32. Ogata K, Tamura H: Thrombopoietin and myelodysplastic syndromes. Int J Hematol; 2000 Aug;72(2):173-7
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  • Thrombopoietin (TPO), a major cytokine involved in megakaryocystopoiesis/thrombopoiesis, may be effective for the treatment of thrombocytopenia associated with myelodysplastic syndromes (MDS).
  • We reviewed the available data relating to the therapeutic potential of TPO for MDS and found the following.
  • The endogenous TPO level is elevated in MDS patients, especially in those with refractory anemia (RA).
  • In RA patients, but not in patients with RA with excess blasts (RAEB) or RAEB in transformation (RAEB-t), both the platelet and megakaryocyte counts correlate inversely with the endogenous TPO level.
  • Meanwhile, in some patients with RAEB, RAEB-t, or chronic myelomonocytic leukemia, blasts have the TPO-R mRNA and probably TPO-R protein.
  • This fact may explain the lack of correlation between the endogenous TPO level and the platelet and megakaryocyte counts in RAEB and RAEB-t and suggests that TPO may induce blast proliferation in some cases.
  • [MeSH-major] Myelodysplastic Syndromes / drug therapy. Thrombopoietin / therapeutic use
  • [MeSH-minor] Anemia, Refractory / drug therapy. Animals. Hematopoiesis / drug effects. Humans. Megakaryocytes / cytology. Megakaryocytes / drug effects. Thrombocytopenia / drug therapy. Thrombocytopenia / etiology

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  • (PMID = 11039665.001).
  • [ISSN] 0925-5710
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] IRELAND
  • [Chemical-registry-number] 9014-42-0 / Thrombopoietin
  • [Number-of-references] 46
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33. Woods WG, Barnard DR, Alonzo TA, Buckley JD, Kobrinsky N, Arthur DC, Sanders J, Neudorf S, Gold S, Lange BJ: Prospective study of 90 children requiring treatment for juvenile myelomonocytic leukemia or myelodysplastic syndrome: a report from the Children's Cancer Group. J Clin Oncol; 2002 Jan 15;20(2):434-40
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  • [Title] Prospective study of 90 children requiring treatment for juvenile myelomonocytic leukemia or myelodysplastic syndrome: a report from the Children's Cancer Group.
  • PATIENTS AND METHODS: Ninety children with JMML, various forms of MDS, or acute myeloid leukemia (AML) with antecedent MDS were treated with a five-drug induction regimen (standard or intensive timing).
  • All other patients were randomized between autologous BMT and aggressive nonmyeloablative chemotherapy.
  • RESULTS: Patients with JMML and refractory anemia (RA) or RA-excess blasts (RAEB) exhibited high induction failure rates and overall remission of 58% and 48%, respectively.
  • Remission rates for patients with RAEB in transformation (RAEB-T) (69%) or antecedent MDS (81%) were similar to de novo AML (77%).
  • Actuarial survival rates at 6 years were as follows: JMML, 31% +/- 26%; RA and RAEB, 29% +/- 16%; RAEB-T, 30% +/- 18%; antecedent MDS, 50% +/- 25%; and de novo AML, 45% +/- 3%.
  • For patients achieving remission, long-term survivors were found in those receiving either allogeneic BMT or chemotherapy.
  • Children with a history of MDS who present with AML do well with AML-type therapy.
  • Patients with RA or RAEB respond poorly to AML induction therapy.
  • The optimum treatment for JMML remains unknown.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myelomonocytic, Acute / drug therapy. Myelodysplastic Syndromes / drug therapy


34. Chang KL, O'Donnell MR, Slovak ML, Dagis AC, Arber DA, Niland JC, Forman SJ: Primary myelodysplasia occurring in adults under 50 years old: a clinicopathologic study of 52 patients. Leukemia; 2002 Apr;16(4):623-31
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  • Cases secondary to chemotherapy or radiotherapy were excluded.
  • Forty-two (81%) of the patients were classified using FAB criteria for blood and bone marrow morphology: refractory anemia (RA), 11; refractory anemia with ringed sideroblasts (RARS), four; refractory anemia with excess blasts (RAEB), 12; chronic myelomonocytic leukemia (CMML), three; refractory anemia with excess blasts in transformation (RAEB-T), 12 patients.
  • For the 49 patients for whom information regarding AML transformation was available, 23 (47%) progressed to acute myeloid leukemia, with an overall median time to progression of 2 months (range 3 weeks to 3 years).
  • In each category except for RARS, approximately half of the patients progressed, with a slightly less median time to progression in RAEB-T than for the other subtypes of MDS.
  • Thirteen patients underwent bone marrow transplantation at the time of presentation of their disease.
  • [MeSH-minor] Adolescent. Adult. Bone Marrow Transplantation. Cell Transformation, Neoplastic / pathology. Chromosome Deletion. Chromosomes, Human, Pair 7 / genetics. Female. Humans. Karyotyping. Male. Middle Aged. Prognosis

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  • (PMID = 11960342.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] England
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35. Xu LP, Huang XJ, Liu KY, Chen H, Liu DH, Han W, Chen YH, Gao ZY, Lu J, Wang JZ, Lu DP: [Allogenic stem cell transplantation from genotypically HLA-identical siblings for 30 patients with myelodysplastic syndromes]. Zhonghua Xue Ye Xue Za Zhi; 2006 Aug;27(8):518-21
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  • OBJECTIVE: To explore the indication and optimum time for treating myelodysplastic syndrome (MDS) by allogeneic hematopoietic stem cell transplantation (allo-HSCT) with HLA identical sibling grafts.
  • On HSCT, 4 patients had refractory anemia (RA) , 2 RA with ringed sideroblasts (RARS) , 7 RA with excess blasts(RAEB) , 14 RAEB in transformation (RAEB-t) , 3 already progressed to secondary AML.
  • RESULTS: The 3-year expected overall survival (OS) was 63.61%, 3-year expected disease-free survival ( DFS) 61.41%, and relapse rate 5.26%; OS for RA/ RAS, RAEB and RAEB-t/AML subgroup was 83.33%, 34.29% and 66.67% , respectively, and all had no statistic difference among them.
  • Pre-HSCT chemotherapy, disease subtype and cGVHD all had no correlation with LFS or OS (P > 0.05).
  • CONCLUSION: For young MDS patients having HLA-identical sibling donors, HSCT should be the first line therapy and performed as soon as possible.


36. Venditti A, Tamburini A, Buccisano F, Scimò MT, Del Poeta G, Maurillo L, Cox MC, Abruzzese E, Tribalto M, Masi M, Amadori S: A phase-II trial of all trans retinoic acid and low-dose cytosine arabinoside for the treatment of high-risk myelodysplastic syndromes. Ann Hematol; 2000 Mar;79(3):138-42
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  • [Title] A phase-II trial of all trans retinoic acid and low-dose cytosine arabinoside for the treatment of high-risk myelodysplastic syndromes.
  • The courses were repeated monthly until response or progression, in the case of response, the therapy was administered until relapse.
  • Morphologic diagnoses were refractory anemia with excess blasts (RAEB) in nine, RAEB in transformation (RAEB-t) in nine, and chronic myelomonocytic leukemia (CMMoL) in four patients; in all cases, bone-marrow blast infiltration was greater than 10% (median 20%, range 12-30%).
  • Nineteen patients were males and three were females; the median age was 69 years (range 25-90 years); three patients had previously been treated with conventional chemotherapy, and one of them had also undergone autologous bone-marrow transplantation.
  • (1) complete response: normalization of blood counts and bone-marrow blasts (<5%), and (2) partial response: decrease in bone-marrow blast infiltration by 50%, and two of the following parameters - improvement in hemoglobin level by 1.5 g/dl or decrease by 50% in transfusional requirement, increase by 50% in absolute neutrophil count, and increase by 50% in platelet count.
  • [MeSH-major] Cytarabine / administration & dosage. Myelodysplastic Syndromes / drug therapy. Tretinoin / administration & dosage
  • [MeSH-minor] Administration, Oral. Adult. Aged. Aged, 80 and over. Anemia / chemically induced. Dose-Response Relationship, Drug. Female. Humans. Hypertriglyceridemia / chemically induced. Infection / chemically induced. Male. Middle Aged. Neutropenia / chemically induced. Thrombocytopenia / chemically induced

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  • (PMID = 10803936.001).
  • [ISSN] 0939-5555
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] GERMANY
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 5688UTC01R / Tretinoin
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37. Zwierzina H, Suciu S, Loeffler-Ragg J, Neuwirtova R, Fenaux P, Beksac M, Harousseau J, Nuessler V, Cermak J, Solbu G, Willemze R, de Witte T, Amadori S, EORTC Leukemia Cooperative Group: Low-dose cytosine arabinoside (LD-AraC) vs LD-AraC plus granulocyte/macrophage colony stimulating factor vs LD-AraC plus Interleukin-3 for myelodysplastic syndrome patients with a high risk of developing acute leukemia: final results of a randomized phase III study (06903) of the EORTC Leukemia Cooperative Group. Leukemia; 2005 Nov;19(11):1929-33
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  • In this randomized phase III study of the EORTC Leukemia Cooperative Group, patients with myelodysplastic syndromes (MDS) with 10-30% bone marrow blasts and hematopoietic failure were treated with low-dose cytosine arabinoside (LD-AraC) (2 x 10 mg/m2/day subcutaneously (s.c.) days 1-14) either alone or in combination with rhGM-CSF or interleukin-3 (IL-3) both given s.c. at a dose of 150 microg/day from day 8 to 21.
  • A total of 180 evaluable patients with a median age of 65 years and refractory anemia with an excess of blasts (RAEB, n = 107) or RAEB in transformation (RAEBt, n = 73) were randomized.
  • There were no differences among the three treatment regimens with respect to numbers of courses applied or treatment delays.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia / prevention & control. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Acute Disease. Adult. Aged. Aged, 80 and over. Cytarabine / administration & dosage. Cytarabine / adverse effects. Female. Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage. Granulocyte-Macrophage Colony-Stimulating Factor / adverse effects. Humans. Injections, Subcutaneous. Interleukin-3 / administration & dosage. Interleukin-3 / adverse effects. Male. Middle Aged. Risk Factors. Treatment Outcome

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  • (PMID = 16151466.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / 5U10-CA11488-20; United States / NCI NIH HHS / CA / 5U10-CA11488-35
  • [Publication-type] Clinical Trial; Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Interleukin-3; 04079A1RDZ / Cytarabine; 83869-56-1 / Granulocyte-Macrophage Colony-Stimulating Factor
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38. Guardiola P, Runde V, Bacigalupo A, Ruutu T, Locatelli F, Boogaerts MA, Pagliuca A, Cornelissen JJ, Schouten HC, Carreras E, Finke J, van Biezen A, Brand R, Niederwieser D, Gluckman E, de Witte TM, Subcommittee for Myelodysplastic Syndromes of the Chronic Leukaemia Working Group of the European Blood and Marrow Transplantation Group: Retrospective comparison of bone marrow and granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells for allogeneic stem cell transplantation using HLA identical sibling donors in myelodysplastic syndromes. Blood; 2002 Jun 15;99(12):4370-8
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  • There were 69 cases of refractory anemia (RA), 86 RA with excess blasts (RAEB), 75 RAEB in transformation (RAEB-t), and 4 unclassified MDS at diagnosis.
  • Multivariate analyses focused on transplantation-related mortality (TRM), 2-year treatment failure incidence, and survival.
  • The incidence of acute GVHD was similar whatever the graft type used.
  • The 2-year treatment failure incidence was significantly decreased with PBPCs, from 38% to 13% (RR, 0.22; 95% CI, 0.10-0.48; P <.001).
  • In conclusion, PBPCs might be preferred for allogeneic transplantation in MDS patients at high risk for relapse on the basis of morphologic criteria because the use of this hematopoietic stem cell was associated with lower treatment failure incidence and improved survival.
  • [MeSH-major] Hematopoietic Stem Cell Mobilization / methods. Hematopoietic Stem Cell Transplantation / methods. Hematopoietic Stem Cells / drug effects. Myelodysplastic Syndromes / therapy. Transplantation Immunology
  • [MeSH-minor] Adolescent. Adult. Bone Marrow Cells / cytology. Child. Child, Preschool. Female. Granulocyte Colony-Stimulating Factor / administration & dosage. Histocompatibility Testing. Humans. Male. Middle Aged. Nuclear Family. Retrospective Studies. Survival Analysis. Transplantation, Isogeneic / immunology. Transplantation, Isogeneic / methods. Transplantation, Isogeneic / mortality. Treatment Outcome


39. Mori T, Aisa Y, Yokoyama A, Nakazato T, Yamazaki R, Shimizu T, Mihara A, Kato J, Watanabe R, Takayama N, Ikeda Y, Okamoto S: Total body irradiation and granulocyte colony-stimulating factor-combined high-dose cytarabine as a conditioning regimen in allogeneic hematopoietic stem cell transplantation for advanced myelodysplastic syndrome: a single-institute experience. Bone Marrow Transplant; 2007 Feb;39(4):217-21
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  • We evaluated 22 patients with advanced MDS, including refractory anemia with excess blasts (RAEB; n=10), RAEB in transformation (n=2), acute myelogenous leukemia transformed from MDS (n=6) and chronic myelomonocytic leukemia (n=4).
  • The conditioning regimen consisted of 12 Gy of TBI and high-dose cytarabine (3 g/m(2)) every 12 h for 4 days, and the cytarabine was combined with continuous administration of G-CSF.
  • These results suggest that G-CSF-combined high-dose cytarabine could be a promising component of the conditioning regimen of allogeneic HSCT for advanced MDS, providing a low incidence of both relapse and treatment-related mortality.
  • [MeSH-major] Cytarabine / administration & dosage. Granulocyte Colony-Stimulating Factor / administration & dosage. Myeloablative Agonists / adverse effects. Myelodysplastic Syndromes / drug therapy. Transplantation Conditioning / methods. Whole-Body Irradiation


40. Mishima Y, Terui Y, Mishima Y, Katsuyama M, Mori M, Tomizuka H, Takizawa T, Miyazato A, Ueda M, Yamada M, Hayasawa H, Mizunuma N, Ishizaka Y, Ikeda K, Kato T, Ozawa K, Hatake K: New human myelodysplastic cell line, TER-3: G-CSF specific downregulation of Ca2+/calmodulin-dependent protein kinase IV. J Cell Physiol; 2002 May;191(2):183-90
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  • We have established a new hematopoietic cell line from a patient with myelodysplastic syndrome (MDS), which was refractory anemia with excess blasts (RAEB).
  • Thus, this cell line has a multilineage phenotype, suggesting that the transformation event occurred in multipotent stem cells.
  • [MeSH-major] Bone Marrow Cells / drug effects. Calcium-Calmodulin-Dependent Protein Kinases / drug effects. Cell Differentiation / drug effects. Cell Division / drug effects. Cell Line / drug effects. Down-Regulation / drug effects. Granulocyte Colony-Stimulating Factor / pharmacology. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Antigens, Surface / metabolism. Calcium-Calmodulin-Dependent Protein Kinase Type 4. Cell Culture Techniques. Cell Size / physiology. DNA / metabolism. Dose-Response Relationship, Drug. Humans. Interleukin-3 / metabolism. Interleukin-3 / pharmacology. Karyotyping. Male. Middle Aged. RNA, Messenger / drug effects. RNA, Messenger / metabolism

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  • (PMID = 12064461.001).
  • [ISSN] 0021-9541
  • [Journal-full-title] Journal of cellular physiology
  • [ISO-abbreviation] J. Cell. Physiol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, Surface; 0 / Interleukin-3; 0 / RNA, Messenger; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 9007-49-2 / DNA; EC 2.7.11.17 / CAMK4 protein, human; EC 2.7.11.17 / Calcium-Calmodulin-Dependent Protein Kinase Type 4; EC 2.7.11.17 / Calcium-Calmodulin-Dependent Protein Kinases
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41. Raza A, Mehdi M, Mumtaz M, Ali F, Lascher S, Galili N: Combination of 5-azacytidine and thalidomide for the treatment of myelodysplastic syndromes and acute myeloid leukemia. Cancer; 2008 Oct 1;113(7):1596-604
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  • [Title] Combination of 5-azacytidine and thalidomide for the treatment of myelodysplastic syndromes and acute myeloid leukemia.
  • BACKGROUND: The treatment of myelodysplastic syndromes (MDS) remains a challenge to the clinician despite recent advances.
  • Many patients will either not respond or will have only limited and/or brief responses to single-agent therapy.
  • Six patients had refractory anemia (RA), 2 patients had RA with ringed sideroblasts, 10 patients had RA with excess blasts (RAEB), 1 patient had RAEB in transformation, 4 patients had chronic myelomonocytic leukemia, 1 patient had chronic idiopathic myelofibrosis, and 16 patients had AML.
  • It was noteworthy that 9 of 14 patients with AML had a history of prior MDS, 2 of 9 patients achieved a CR, 4 of 9 patients had HI (HI-E and bilineage HI), and 1 patient had stable disease and was continuing treatment.
  • CONCLUSIONS: The current findings indicated that a combination of low-dose AZA and thalidomide was well tolerated and was effective therapy for the treatment of patients with MDS and AML arising from prior MDS.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Azacitidine / administration & dosage. Leukemia, Myeloid, Acute / drug therapy. Myelodysplastic Syndromes / drug therapy. Thalidomide / administration & dosage
  • [MeSH-minor] Bone Marrow Cells / pathology. Drug Administration Schedule. Humans. Oligonucleotide Array Sequence Analysis. Pilot Projects. Survival Analysis. Treatment Outcome


42. Honda M, Yamada Y, Tomonaga M, Ichinose H, Kamihira S: Correlation of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, and clinical features of hematological disorders: a pilot study. Leuk Res; 2000 Jun;24(6):461-8
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  • The pre-therapy level of urinary 8-OHdG in ATL patients was significantly elevated compared with normal controls (25.3+/-12.9 vs. 11.9+/-7.3 ng/mg, P<0.05).
  • However, two patients with refractory anemia with excess blasts in transformation (RAEB-t) having extreme monocytosis and neutrophilia showed exceptionally high urinary 8-OHdG levels (161.0 and 218.9 ng/mg).
  • Urinary 8-OHdG excretion increased transiently with chemotherapy, and this fluctuation was significant irrespective of the disorder (P<0.05).
  • [MeSH-minor] Adult. Aged. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Chromatography, High Pressure Liquid. Enzyme-Linked Immunosorbent Assay. Female. Humans. Male. Middle Aged. Oxidative Stress. Pilot Projects

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  • (PMID = 10781678.001).
  • [ISSN] 0145-2126
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] ENGLAND
  • [Chemical-registry-number] 88847-89-6 / 8-oxo-7-hydrodeoxyguanosine; G9481N71RO / Deoxyguanosine
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43. Harada H, Harada Y, Kimura A: Implications of somatic mutations in the AML1/RUNX1 gene in myelodysplastic syndrome (MDS): future molecular therapeutic directions for MDS. Curr Cancer Drug Targets; 2006 Sep;6(6):553-65
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  • [Title] Implications of somatic mutations in the AML1/RUNX1 gene in myelodysplastic syndrome (MDS): future molecular therapeutic directions for MDS.
  • MDS is also a susceptibility to acute myeloid leukemia (AML) and shown to be extremely resistant to current therapeutic strategies.
  • MDS in a subset of 10-20% of patients arise after previous chemotherapy or radiation exposure for other malignancies.
  • Recently, we reported the high incidence of somatic mutations in the AML1/RUNX1 gene, which is a critical regulator of definitive hematopoiesis and the most frequent target for translocation of AML, in MDS, especially refractory anemia with excess blasts (RAEB), RAEB in transformation (RAEBt) and AML following MDS (defined here as MDS/AML).
  • Normalizing AML1 function or regulating cooperative gene mutations would provide an important clue for molecular target therapies.
  • [MeSH-major] Core Binding Factor Alpha 2 Subunit / genetics. Genetic Therapy / trends. Mutation. Myelodysplastic Syndromes / genetics. Myelodysplastic Syndromes / therapy






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