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1. Papenhausen PR, Griffin S, Tepperberg J: Oncogene amplification in transforming myelodysplasia. Exp Mol Pathol; 2005 Oct;79(2):168-75
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  • The MLL gene, located within band 11q23, has been shown to be involved in translocations with a large variety of reciprocal sites in both lymphoid and myeloid leukemia and has also been shown to undergo submicroscopic self-fusion/partial duplication.
  • In all MLL cases, the patients were clinically classified as having transforming myelodysplasia (RAEB/RAEBT) or AML.
  • Four patients had been previously diagnosed with cancer and had received topoisomerase II targeted drug therapy which is known to be associated with fusion transcripts involving the MLL and AML1 genes.
  • All of our patients rapidly developed refractory AML.
  • The frequency and clinical correlations of MLL gene amplification in leukemia will need careful follow-up, since the frequently cryptic amplification described in these cases may not generally provoke confirmatory FISH studies.
  • Both genes also show a high degree of diversity of pathogenic mechanisms of leukemia evolution, including numerous reciprocal fusion genes in transformation to either AML or ALL and gain of function amplification.
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Chromosome Aberrations. Core Binding Factor Alpha 2 Subunit. Female. Histone-Lysine N-Methyltransferase. Humans. In Situ Hybridization, Fluorescence. Male. Middle Aged. Myeloid-Lymphoid Leukemia Protein. Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics. Proto-Oncogene Proteins / genetics

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  • (PMID = 16026782.001).
  • [ISSN] 0014-4800
  • [Journal-full-title] Experimental and molecular pathology
  • [ISO-abbreviation] Exp. Mol. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Core Binding Factor Alpha 2 Subunit; 0 / DNA-Binding Proteins; 0 / MLL protein, human; 0 / Proto-Oncogene Proteins; 0 / RUNX1 protein, human; 0 / Transcription Factors; 149025-06-9 / Myeloid-Lymphoid Leukemia Protein; EC 2.1.1.43 / Histone-Lysine N-Methyltransferase
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2. Ebihara Y, Manabe A, Tsuruta T, Ishikawa K, Hasegawa D, Ohtsuka Y, Kawasaki H, Ogami K, Wada Y, Kanda T, Tsuji K: The effect of donor leukocyte infusion on refractory pure red blood cell aplasia after allogeneic stem cell transplantation in a patient with myelodysplastic syndrome developing from Kostmann syndrome. Int J Hematol; 2007 Dec;86(5):446-50
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  • [Title] The effect of donor leukocyte infusion on refractory pure red blood cell aplasia after allogeneic stem cell transplantation in a patient with myelodysplastic syndrome developing from Kostmann syndrome.
  • We describe the clinical course of a patient who experienced refractory pure red cell aplasia (PRCA) after undergoing HLA-matched allogeneic peripheral blood stem cell transplantation (allo-PBSCT) for refractory anemia with an excess of blasts in transformation that had evolved from Kostmann syndrome.
  • The treatment for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) developing from Kostmann syndrome has not been standardized.
  • We treated this patient with allo-PBSCT using a regimen combining high-dose cytosine arabinoside with granulocyte colony-stimulating factor, in addition to total body irradiation and cyclophosphamide without preceding intensive chemotherapy.
  • Erythroid engraftment was not evident, however, and the patient was given a diagnosis of PRCA.
  • Regimen-related toxicity and graft-versus-host disease (GVHD) were limited.
  • The PRCA did not respond to various therapies, including the discontinuation of immunosuppressants for the induction of chronic GVHD, human recombinant erythropoietin, immunosuppressive treatment with steroids, cyclosporin A, and human anti-CD20 antibody (rituximab).
  • The patient received transfusions 48 times until the resolution of his anemia by donor leukocyte infusion (DLI) at 25 months after PBSCT.
  • The results indicate that the conditioning regimen we describe seems safe and effective for those who have MDS/AML and that DLI might be a valuable approach for refractory PRCA after ABO-incompatible SCT.
  • [MeSH-major] Leukocyte Transfusion. Living Donors. Myelodysplastic Syndromes / therapy. Myelopoiesis. Peripheral Blood Stem Cell Transplantation. Red-Cell Aplasia, Pure / therapy


3. Su YW, Chang MC, Chiang MF, Hsieh RK: Treatment-related myelodysplastic syndrome after temozolomide for recurrent high-grade glioma. J Neurooncol; 2005 Feb;71(3):315-8
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  • [Title] Treatment-related myelodysplastic syndrome after temozolomide for recurrent high-grade glioma.
  • In patients with recurrent malignant glioma, treatment-related myelodysplastic syndrome (t-MDS) and acute leukemia are rare adverse effects because the median survival after relapse is limited.
  • We report a 44-year-old woman with t-MDS (refractory anemia with excess blasts) following treatment of recurrent anaplastic astrocytoma with temozolomide (TMZ).
  • The disease rapidly evolved into acute leukemia within 1 month after the onset of MDS, and the patient died 1 month later during induction chemotherapy.
  • The prognosis of t-MDS is generally poor.
  • Considering the increasing use of TMZ, which is regarded as a drug with moderate toxicity, careful follow-up with routine blood testing is vital.
  • [MeSH-major] Antineoplastic Agents, Alkylating / adverse effects. Astrocytoma / drug therapy. Brain Neoplasms / drug therapy. Dacarbazine / adverse effects. Dacarbazine / analogs & derivatives. Leukemia / chemically induced. Myelodysplastic Syndromes / chemically induced. Neoplasm Recurrence, Local / drug therapy
  • [MeSH-minor] Acute Disease. Adult. Chromosomes, Human, Pair 11. Fatal Outcome. Female. Gene Deletion. Humans


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4. 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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5. Lee ST, Jang JH, Suh HC, Hahn JS, Ko YW, Min YH: Idarubicin, cytarabine, and topotecan in patients with refractory or relapsed acute myelogenous leukemia and high-risk myelodysplastic syndrome. Am J Hematol; 2001 Dec;68(4):237-45
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  • [Title] Idarubicin, cytarabine, and topotecan in patients with refractory or relapsed acute myelogenous leukemia and high-risk myelodysplastic syndrome.
  • In an effort to develop more effective therapy for patients with refractory or relapsed acute myelogenous leukemia (AML) and high-risk myelodysplastic syndrome (MDS), we investigated the efficacy of a combination chemotherapy consisting of idarubicin, cytarabine, and topotecan.
  • Twenty-seven patients were treated: four with primary refractory AML, nine with AML in first relapse, four with AML in second relapse, and 10 with MDS-RAEB/RAEBT.
  • Patients received as salvage therapy a single course of idarubicin 12 mg/m(2) IV bolus on days 1-3, cytarabine 1 g/m(2) over two hours q 12 hr on days 1-5, and topotecan 1.25 mg/m(2) over 24 hr on days 1-5.
  • Thirteen AML patients (excluding four relapsed after autologous stem cell transplantation) were grouped into four categories to stratify the probability of achieving complete remission (CR): group 1, first CR duration > or = 2 years and receiving first salvage treatment (S1); group 2, first CR duration 1-2 years and receiving S1; group 3, first CR duration 0-1 years and receiving S1; and group 4, first CR duration 0-1 years and receiving S2, S3, or S4 after failing S1.
  • Median duration of survival in 10 MDS patients was 15 months, and all four MDS patients achieving a CR maintained continuous CR with a median follow-up of 11 months.
  • Median time to recovery of neutrophils > or =0.5 x 10(9)/l was 22 days (11-34) and for platelets > 20 x 10(9)/l 35 days (11-58).
  • We conclude that combination chemotherapy with intermediate dose cytarabine, idarubicin, and topotecan has significant antileukemic activity and acceptable toxicity in salvage AML and high-risk MDS.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Leukemia, Myeloid, Acute / drug therapy. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Cytarabine / administration & dosage. Cytarabine / toxicity. Disease-Free Survival. Female. Humans. Idarubicin / administration & dosage. Idarubicin / toxicity. Male. Middle Aged. Remission Induction. Salvage Therapy. Survival Rate. Topotecan / administration & dosage. Topotecan / toxicity. Treatment Outcome


6. Sasaki H, Manabe A, Kojima S, Tsuchida M, Hayashi Y, Ikuta K, Okamura I, Koike K, Ohara A, Ishii E, Komada Y, Hibi S, Nakahata T, MDS Committee of the Japanese Society of Pediatric Hematology, Japan: Myelodysplastic syndrome in childhood: a retrospective study of 189 patients in Japan. Leukemia; 2001 Nov;15(11):1713-20
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • In total, 189 patients were enrolled: 122 cases of primary MDS (26 RA, 18 RAEB, 25 RAEBt, 53 CMML/JMML), 24 cases with constitutional predisposition to MDS, and 43 cases of therapy-related MDS (t-MDS).
  • The frequency of pediatric MDS was estimated to be 7.7% of all leukemias.
  • Cytogenetic abnormalities were observed in 41% of primary MDS and 90% of t-MDS cases.
  • The 4-year survival rate, estimated by Kaplan-Meier analysis, for primary RA was 78.9%, while other types of MDS and JMML had rates lower than 40%, and t-MDS showed an even more unfavorable prognosis.
  • There was no apparent advantage to chemotherapy for RA, and the survival rate in patients with primary RA, JMML, or t-MDS receiving stem cell transplantation was significantly higher.
  • More precise designs of our diagnostic and classification systems, as well as therapeutic trials in large-scale prospective studies, are necessary for further improvements in MDS outcome.
  • [MeSH-major] Myelodysplastic Syndromes / diagnosis. Myelodysplastic Syndromes / mortality
  • [MeSH-minor] Adolescent. Child. Child, Preschool. Cytogenetic Analysis. Female. Humans. Infant. Japan. Male. Prognosis. Retrospective Studies. Survival Rate. Treatment Outcome


7. Witherspoon RP, Deeg HJ, Storer B, Anasetti C, Storb R, Appelbaum FR: Hematopoietic stem-cell transplantation for treatment-related leukemia or myelodysplasia. J Clin Oncol; 2001 Apr 15;19(8):2134-41
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  • [Title] Hematopoietic stem-cell transplantation for treatment-related leukemia or myelodysplasia.
  • PURPOSE: This report describes results of related or unrelated hematopoietic stem-cell transplants in 111 patients with treatment-related leukemia or myelodysplasia performed consecutively at the Fred Hutchinson Cancer Research Center between December 1971 and June 1998, and identifies patient and treatment characteristics associated with survival and relapse.
  • PATIENTS AND METHODS: At transplantation, 56 patients had treatment-related secondary acute myeloid leukemia (AML), 15 had refractory anemia with excess blasts in transition (RAEB-T), 23 had refractory anemia with excess blasts (RAEB), 15 had refractory anemia (RA), and two had refractory anemia with ringed sideroblasts (RARS).
  • Conditioning regimens were total-body irradiation (TBI) and chemotherapy for 60 patients, busulfan (BU) 14 to 16 mg/kg and cyclophosphamide (CY) 120 mg/kg (BUCY) for 27 patients, BU targeted to 600 to 900 ng/mL plasma steady-state concentration with 120 mg/kg CY (BUCY-t) for 22 patients, and miscellaneous chemotherapy for two patients.
  • RESULTS: The 5-year disease-free survival was 8% for TBI, 19% for BUCY, and 30% for BUCY-t (P =.006).
  • The 5-year cumulative incidence of relapse was 40% for secondary AML, 40% for RAEB-T, 26% for RAEB, and 0% for RA or RARS (P =.0009).
  • CONCLUSION: Patients at risk for treatment-related leukemia or myelodysplasia should be followed closely and be considered for stem-cell transplantation early in the course of myelodysplasia using conditioning regimens such as BUCY-t designed to reduce nonrelapse mortality.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Hematopoietic Stem Cell Transplantation. Leukemia, Myeloid, Acute / therapy. Myelodysplastic Syndromes / therapy. Neoplasms, Second Primary / therapy
  • [MeSH-minor] Adult. Busulfan / administration & dosage. Cyclophosphamide / administration & dosage. Disease-Free Survival. Follow-Up Studies. Hematopoietic Stem Cell Mobilization. Humans. Mortality. Prognosis. Retrospective Studies. Transplantation, Autologous. Transplantation, Homologous. Whole-Body Irradiation

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  • (PMID = 11304765.001).
  • [ISSN] 0732-183X
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Grant] United States / NIAID NIH HHS / AI / AI33484; United States / NCI NIH HHS / CA / CA15704; United States / NCI NIH HHS / CA / CA18029; United States / NCI NIH HHS / CA / CA18221; United States / NHLBI NIH HHS / HL / HL36444; United States / NCI NIH HHS / CP / N01-CP51027
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 8N3DW7272P / Cyclophosphamide; G1LN9045DK / Busulfan
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8. Ogasawara T, Yasuyama M, Kawauchi K: Therapy-related myelodysplastic syndrome with monosomy 5 after successful treatment of acute myeloid leukemia (M2). Am J Hematol; 2005 Jun;79(2):136-41
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  • [Title] Therapy-related myelodysplastic syndrome with monosomy 5 after successful treatment of acute myeloid leukemia (M2).
  • We describe a patient who developed myelodysplastic syndrome over 2 years after achieving complete remission of acute myeloid leukemia (AML).
  • The patient was treated in July 1998 with anthracycline, etoposide, and behenoyl cytarabine chemotherapy for AML (French-American-British classification, M2; World Health Organization classification, AML with maturation) and achieved complete remission.
  • In December 2000, the patient's peripheral blood revealed pancytopenia, and his bone marrow was hypocellular with trilineage myelodysplasia and no blasts.
  • The patient was diagnosed with high-grade myelodysplastic syndrome (MDS)/refractory anemia with excess blasts (RAEB) subtype.
  • The pancytopenia progressed rapidly, and he died 2 months after the diagnosis of MDS.
  • Therapy-related MDS and AML (t-MDS/t-AML) developing after treatment for acute leukemia is unusual; the primary leukemia associated with most cases of t-MDS/t-AML is acute promyelocytic leukemia (APL).
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / adverse effects. Chromosomes, Human, Pair 5. Cytarabine / analogs & derivatives. Leukemia, Myeloid, Acute / chemically induced. Monosomy. Myelodysplastic Syndromes / chemically induced. Myelodysplastic Syndromes / genetics


9. Yamada T, Tsurumi H, Kasahara S, Hara T, Sawada M, Moriwaki H: Immunosuppressive therapy for myelodysplastic syndrome: efficacy of methylprednisolone pulse therapy with or without cyclosporin A. J Cancer Res Clin Oncol; 2003 Aug;129(8):485-91
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  • [Title] Immunosuppressive therapy for myelodysplastic syndrome: efficacy of methylprednisolone pulse therapy with or without cyclosporin A.
  • We investigated whether immunosuppressive therapy using methylprednisolone (mPSL) with or without cyclosporin A (CsA) could benefit patients with myelodysplastic syndrome (MDS).
  • Eligibility criteria for this study were a clinical diagnosis of MDS with less than 5% blast in peripheral blood, less than 10% blast in bone marrow and advanced cytopenia.
  • Among 73 patients with MDS, 18 eligible and consecutive patients (8 men and 10 women), aged 48 to 87 years (median: 66.5 years) were assigned to receive mPSL pulse therapy (1,000 mg daily for 3 consecutive days, followed by tapering oral prednisolone; n= 12) or mPSL pulse with CsA therapy (4 to 5 mg/kg administered twice daily; n= 6).
  • Six of 18 patients (33.3%; 3 of 10 patients with RA, 2 of 6 patients with RAEB, 1 of 2 patients with CMMoL) responded to immunosuppressive therapy.
  • One of 6 patients with hypocellular bone marrow and 5 of 12 patients with normocellular or hypercellular marrow responded to immunosuppressive therapy.
  • No patient with myelofibrosis responded to the therapy.
  • Although a significant difference was observed between responders and nonresponders in the survival rate ( P<0.05), no significant difference was found in clinical characteristics at entry between responders and nonresponders.
  • It is possible that immunosuppressive therapy might be effective for a certain subset of patients with MDS.
  • [MeSH-major] Cyclosporine / administration & dosage. Immunosuppressive Agents / therapeutic use. Methylprednisolone / administration & dosage. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Aged. Aged, 80 and over. Drug Therapy, Combination. Female. Hemoglobins / drug effects. Humans. Male. Middle Aged. Pulse Therapy, Drug. Survival Analysis. Treatment Outcome


10. Bennett JM, Young MS, Liesveld JL, Paietta E, Miller KB, Lazarus HM, Marsh RD, Friedenberg WR, Saba HT, Hayes FA, Dewald GW, Hiddemann W, Rowe JM: Phase II study of combination human recombinant GM-CSF with intermediate-dose cytarabine and mitoxantrone chemotherapy in patients with high-risk myelodysplastic syndromes (RAEB, RAEBT, and CMML): an Eastern Cooperative Oncology Group Study. Am J Hematol; 2001 Jan;66(1):23-7
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  • [Title] Phase II study of combination human recombinant GM-CSF with intermediate-dose cytarabine and mitoxantrone chemotherapy in patients with high-risk myelodysplastic syndromes (RAEB, RAEBT, and CMML): an Eastern Cooperative Oncology Group Study.
  • A Phase II study of GM-CSF with intermediate-dose cytarabine and mitoxantrone was conducted in patients with high-risk myelodysplastic syndrome.
  • It was designed to evaluate if priming with growth factor could increase the efficiency of chemotherapy.
  • In this older population only two of 10 patients achieved a bone marrow CR, including one patient whose leukemic blasts had an "S" phase increase of 2.55x at 48 hr.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Aged. Anemia, Refractory, with Excess of Blasts / drug therapy. Anemia, Refractory, with Excess of Blasts / mortality. Anemia, Refractory, with Excess of Blasts / pathology. Bone Marrow / pathology. Cytarabine / administration & dosage. Cytarabine / adverse effects. DNA Replication / drug effects. Drug-Induced Liver Injury / etiology. Female. Humans. Hyperbilirubinemia / chemically induced. Leukemia, Myelomonocytic, Chronic / drug therapy. Leukemia, Myelomonocytic, Chronic / mortality. Leukemia, Myelomonocytic, Chronic / pathology. Male. Middle Aged. Mitoxantrone / administration & dosage. Mitoxantrone / adverse effects. Pancytopenia / chemically induced. Pancytopenia / drug therapy. Pilot Projects. Recombinant Proteins. Remission Induction. S Phase / drug effects. Treatment Failure

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  • (PMID = 11426487.001).
  • [ISSN] 0361-8609
  • [Journal-full-title] American journal of hematology
  • [ISO-abbreviation] Am. J. Hematol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA07190; United States / NCI NIH HHS / CA / CA11083; United States / NCI NIH HHS / CA / CA23318; etc
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Recombinant Proteins; 04079A1RDZ / Cytarabine; 123774-72-1 / sargramostim; 83869-56-1 / Granulocyte-Macrophage Colony-Stimulating Factor; BZ114NVM5P / Mitoxantrone
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11. Millard TP, Aitchison R, Wilkinson JD: Aleukaemic leukaemia cutis presenting as a benign-appearing eruption. Clin Exp Dermatol; 2003 Mar;28(2):148-50
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  • [Title] Aleukaemic leukaemia cutis presenting as a benign-appearing eruption.
  • A 68-year-old Caucasian male presented with a 5-week history of a widespread pruritic papular eruption.
  • Histology from a papule on the left shoulder showed a dense dermal infiltrate of large mononuclear cells which were positive for leucocyte common antigen, KP1 and PGM1, with an MIB-1 proliferating fraction of 40%, diagnostic of acute monocytic (M5) leukaemia cutis.
  • Full blood count revealed pancytopaenia but no blasts.
  • Bone marrow aspirate showed reduced red cell precursors and 10% blasts, consistent with myelodysplastic syndrome (refractory anaemia with excess blasts).
  • The patient was managed with a 3 unit transfusion of packed red cells, after which his skin eruption resolved within 6 weeks and his peripheral blood counts returned to normal.
  • No chemotherapy was administered.
  • In conclusion, leukaemia can present in the skin, the eruption may be nonspecific and it may precede systemic involvement by either myelodysplastic syndrome or acute leukaemia.
  • [MeSH-major] Leukemia / pathology. Leukemia, Myeloid / pathology. Skin Neoplasms / pathology

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  • (PMID = 12653700.001).
  • [ISSN] 0307-6938
  • [Journal-full-title] Clinical and experimental dermatology
  • [ISO-abbreviation] Clin. Exp. Dermatol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
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12. 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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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [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.
  • The overall survival of the study group appeared to be prolonged in comparison with a historical control group of patients treated with LDAraC alone.
  • It is suggested that M-CSF added to the administration of LDAraC plays an active role in the therapy.
  • No therapy-related death occurred.
  • Some unique actions of M-CSF were suggested in this trial.
  • 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


13. 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.
  • The median relapse-free survival was 12.5 months, with a probability of ongoing CR at 6.5 years of 19%.
  • 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


14. 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.
  • Eventually, 30% of patients with MDS will progress and develop acute myeloid leukemia (AML).
  • 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.
  • RESULTS: A hematologic improvement (HI) was observed in 15 of 36 patients (42%), stable disease was observed in 5 of 36 patients (14%), and 10 of 36 patients (28%) had disease progression.
  • 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


15. Jang GD, Kim SW, Suh CW, Kim EK, Bahng HS, Jeong YH, Park IG, Kim WK, Kim SH, Suh EJ, Park CJ, Ji HS, Lee JS: A case of treatment-related myelodysplastic syndrome and acute myelogenous leukemia following high-dose chemotherapy with autologous stem cell transplantation for non-Hodgkin's lymphoma. J Korean Med Sci; 2002 Aug;17(4):555-9
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  • [Title] A case of treatment-related myelodysplastic syndrome and acute myelogenous leukemia following high-dose chemotherapy with autologous stem cell transplantation for non-Hodgkin's lymphoma.
  • Treatment-related myelodysplastic syndrome (t-MDS) and acute myelogenous leukemia (t-AML) are now well established as complications of cytotoxic chemotherapy.
  • We experienced a 28-yr-old female patient who developed t-MDS/t-AML with characteristic chromosomal abnormalities including 11q23 chromosomal rearrangement following high-dose chemotherapy with autologous stem cell transplantation (ASCT) for non-Hodgkin's lymphoma.
  • After 2 cycles of systemic chemotherapy of the Vanderbilt regimen, the patient underwent ASCT with high dose chemotherapy of the BEAC regimen.
  • She also received radiation of 48 Gy for the residual periportal lymphadenopathy.
  • The patient was diagnosed as t-MDS (refractory anemia with an excess of blasts).
  • Cytogenetic analysis showed complex chromosomal abnormalities including 11q23 rearrangement, which is frequently found in topoisomerase II inhibitor-related hematologic malignancies.
  • The patient was treated with combination chemotherapy, but her leukemic cells were resistant to the therapy.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / adverse effects. Carmustine / adverse effects. Cyclophosphamide / adverse effects. Cytarabine / adverse effects. Etoposide / adverse effects. Hematopoietic Stem Cell Transplantation / adverse effects. Leukemia, Myeloid, Acute / etiology. Lymphoma, Non-Hodgkin / therapy. Myelodysplastic Syndromes / etiology. Neoplasms, Second Primary / etiology. Pregnancy Complications, Neoplastic / therapy
  • [MeSH-minor] Adult. Antineoplastic Agents, Phytogenic / adverse effects. B-Lymphocytes / cytology. Bone Marrow Cells / pathology. Chromosome Aberrations. Chromosomes, Human, Pair 11. Combined Modality Therapy / adverse effects. Female. Gene Rearrangement. Humans. Pelvis. Pregnancy. Transplantation, Autologous


16. 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.
  • Twenty-two patients with high-risk myelodysplastic syndrome (HRMDS) were treated with a 10-day course of oral all trans retinoic acid (45 mg/m2) and s.c. low-dose cytosine arabinoside (LDARAc) given at the dose of 20 mg twice per day.
  • 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.
  • Fifteen (68%) patients did not achieve any response, and 14 died of progressive disease or infectious disease.
  • [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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17. 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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  • [Title] Correlation of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, and clinical features of hematological disorders: a pilot study.
  • In the present study, urinary 8-OHdG was examined in 44 patients with hematological disorders (13 malignant lymphoma, 11 adult T cell leukemia/lymphoma (ATL), 10 acute leukemia, and 10 myelodysplastic syndrome (MDS)) by an enzyme-linked immunosorbent assay.
  • 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).
  • Although patients with lymphoma, acute leukemia and MDS also showed higher urinary 8-OHdG levels than normal controls, the differences were not significant.
  • 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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18. Rossi S, Canal F, Licci S, Zanatta L, Laurino L, Gottardi M, Gherlinzoni F, Dei Tos AP: Cytogenetic evidence of metastatic myxoid liposarcoma and therapy-related myelodysplastic syndrome in a bone marrow biopsy. Hum Pathol; 2009 Jul;40(7):1040-4
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  • [Title] Cytogenetic evidence of metastatic myxoid liposarcoma and therapy-related myelodysplastic syndrome in a bone marrow biopsy.
  • Myxoid liposarcoma exhibits a peculiar clinical behavior, with a tendency to spread to serosal membranes, distant soft tissues, and bones, even in the absence of lung metastases.
  • Therapy-related hematological neoplasms are well-known side effects of cytotoxic chemotherapy.
  • We describe an exceptional case of metastatic myxoid liposarcoma of the spine associated with therapy-related refractory anemia with excess of blasts in a 37-year-old woman who underwent multi-agent chemotherapy for a myxoid liposarcoma of the left thigh.
  • Microscopic examination of the bone marrow biopsy revealed dysplastic features, with abnormal localization of immature precursors and micromegakaryocytes, and islands of undifferentiated oval small/medium-size cells, suggestive of acute myeloid leukemia arising in the setting of a myelodysplastic syndrome.
  • Cytogenetic analyses of bone marrow aspirate disclosed the presence of 2 different rearrangements, subsequently confirmed by fluorescent in situ hybridization and was crucial in making the correct diagnosis.
  • [MeSH-minor] Adult. Anemia, Refractory / pathology. Antineoplastic Combined Chemotherapy Protocols / adverse effects. Bone Marrow Cells / pathology. Chromosomes, Human, Pair 11. Combined Modality Therapy / adverse effects. Female. Humans. Leukemia, Myeloid, Acute / pathology. Soft Tissue Neoplasms / pathology. Thigh / pathology


19. 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.
  • METHODS: In the Cancer and Leukemia Group B (CALGB) 9221 study, patients with any French-American-British (FAB) subtype of MDS were randomized to azacitidine or best supportive care (BSC).
  • After 56 d, patients randomized to BSC with disease progression could cross over to receive azacitidine.
  • 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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  • (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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20. Fujimaki K, Taguchi J, Fujita H, Hattori M, Yamazaki E, Takahashi N, Fujisawa S, Kanamori H, Maruta A, Ishigatsubo Y: Thiotepa/cyclophosphamide/TBI as a conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome. Bone Marrow Transplant; 2004 Apr;33(8):789-92
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  • Four patients had low-risk disease (refractory anemia or complete remission after chemotherapy) and 14 patients had high-risk disease (RAEB, RAEB-t, or AML).
  • Grade II-IV acute GVHD developed in six patients and chronic GVHD in 10.
  • With a median follow-up of 31 months, the 2-year survival probability is 75% for low-risk patients and 57% for high-risk patients.
  • One patient died of leukemia and six of treatment-related causes.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Hematopoietic Stem Cell Transplantation. Myelodysplastic Syndromes / therapy
  • [MeSH-minor] Adult. Antineoplastic Agents, Alkylating / administration & dosage. Combined Modality Therapy. Cyclophosphamide / administration & dosage. Female. Graft vs Host Disease / etiology. Humans. Male. Middle Aged. Thiotepa / administration & dosage. Transplantation Conditioning. Transplantation, Homologous. Whole-Body Irradiation


21. Bönig H, Körholz D, Lex C, Wölfel S, Göbel U: Monocyte deactivation and its reversal in a patient with chemotherapy-induced leukopenia and severe systemic infection. Med Pediatr Oncol; 2000 Jan;34(1):39-42
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  • [Title] Monocyte deactivation and its reversal in a patient with chemotherapy-induced leukopenia and severe systemic infection.
  • PROCEDURE: A 14-year-old patient with RAEB-T/hypoplastic M2 and chemothera py-induced neutropenia developed a severe infection and continued to deteriorate clinically despite maximum supportive measures, including broad antibacterial and antifungal coverage.
  • On the basis of monocyte de-activation this patient was considered to be in the immunoparalytic phase of sepsis and consequently treated with 60 microg/m(2) of interferon-gamma per day for 10 days.
  • RESULTS: The patient made a rapid clinical recovery, and biochemical markers of infection improved promptly.
  • At the same time, the fraction of activated monocytes normalized rapidly and stably.
  • We hypothesize that treatment with interferon-gamma effected this rapid restoral of monocyte activation and that monocyte reactivation might have contributed to the patient's prompt recovery from his severe infection.
  • Interferon-gamma treatment was well tolerated.
  • CONCLUSIONS: Immunostimulation with interferon-gamma might prove to be a valuable adjuvant treatment for patients with chemotherapy-induced neutropenia during the rare scenario of infection with immunoparalysis.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / adverse effects. Interferon-gamma / therapeutic use. Leukopenia / drug therapy. Monocytes / drug effects. Sepsis / drug therapy
  • [MeSH-minor] Adolescent. Anemia, Refractory, with Excess of Blasts / drug therapy. C-Reactive Protein / drug effects. C-Reactive Protein / metabolism. Humans. Leukocyte Count / drug effects. Male

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  • [Copyright] Copyright 2000 Wiley-Liss, Inc.
  • (PMID = 10611583.001).
  • [ISSN] 0098-1532
  • [Journal-full-title] Medical and pediatric oncology
  • [ISO-abbreviation] Med. Pediatr. Oncol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 82115-62-6 / Interferon-gamma; 9007-41-4 / C-Reactive Protein
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22. Hiçsönmez G, Tunç B, Olcay L, Tuncer MA: Effect of short-course, high-dose steroid therapy in a child with myelodysplastic syndrome. Pediatr Hematol Oncol; 2001 Dec;18(8):525-9
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  • [Title] Effect of short-course, high-dose steroid therapy in a child with myelodysplastic syndrome.
  • High-dose methylprednisolone (HDMP) has been shown to induce differentiation of myeloid leukemic cells with a remarkable antileukemic effect in children with various subtypes of acute myeloblastic leukemia (AML).
  • Here the beneficial effect of short-course HDMP therapy in a child with myelodysplastic syndrome (MDS) is reported.
  • Oral methylprednisolone sodium succinate (Prednol-L) was administered at a single daily dose of 30 mg/kg for 5 days to a 4-year-old girl with refractory anemia with excess of blasts and hypocellular bone marrow before the initiation of chemotherapy.
  • In addition to dramatic clinical improvement, the patient's white blood cell count increased from 2.3 x 10(9)/L to 5.0 x 10(9)/L, and peripheral blood blast cells disappeared 4 days after HDMP treatment.
  • Repeated bone marrow aspirate 1 week after the initiation of HDMP disclosed increased cellularity with no blasts.
  • Furthermore, short-course HDMP treatment stimulated the increase in the number of peripheral blood lymphocytes and CD3+, CD4+, CD8+, CD19+, CD34+, and NK cells.
  • Results obtained with HDMP from the previous studies and the present case suggest that high-dose methylprednisolone is a promising agent in the treatment of AIDS and it is recommended as an initial treatment especially for MDS children with hypocellular bone marrow at presentation.
  • [MeSH-major] Methylprednisolone Hemisuccinate / administration & dosage. Myelodysplastic Syndromes / drug therapy. Steroids / administration & dosage
  • [MeSH-minor] Anemia, Refractory, with Excess of Blasts / drug therapy. Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Blood Cell Count. Bone Marrow / drug effects. Bone Marrow / pathology. Child, Preschool. Female. Humans. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Remission Induction. Treatment Outcome


23. Hui CH, Bardy P, Hughes T, Horvath N, To LB: Successful salvage of RAEB/AML relapsing early post allograft with FLAG-Ida conditioned mini-allograft: a report of two cases. Clin Lab Haematol; 2001 Apr;23(2):135-8
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  • [Title] Successful salvage of RAEB/AML relapsing early post allograft with FLAG-Ida conditioned mini-allograft: a report of two cases.
  • We report, in two such patients, the use of re-induction with FLAG-Ida chemotherapy, followed by the infusion of GCSF-mobilized blood stem cells from the same HLA-matched donor.
  • Both patients achieved durable complete remissions with good quality of life and longer disease-free survival than after the first myeloablative allografts.
  • This mini-allograft approach offers a practical, well-tolerated salvage and a potentially curative treatment for relapsed AML/high grade MDS patients failing a first conventional myeloablative allogeneic transplants.
  • [MeSH-major] Anemia, Refractory, with Excess of Blasts. Hematopoietic Stem Cell Transplantation. Leukemia, Myeloid, Acute. Vidarabine / analogs & derivatives
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cytarabine / therapeutic use. Female. Filgrastim. Granulocyte Colony-Stimulating Factor / therapeutic use. Humans. Idarubicin / therapeutic use. Middle Aged. Recombinant Proteins. Recurrence. Salvage Therapy. Transplantation, Homologous

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  • (PMID = 11488854.001).
  • [ISSN] 0141-9854
  • [Journal-full-title] Clinical and laboratory haematology
  • [ISO-abbreviation] Clin Lab Haematol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [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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24. Niu Y, Chen SC, Jiang B, Li DG, Ge CW, Li RS: [Erythroleukemia - a subtype of myelodysplastic syndrome?]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2007 Apr;15(2):219-23
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  • In order to study whether erythroleukemia was really a subtype of acute leukemia, the clinical laboratory characteristics and development of disease in 21 cases of erythroleukemia were analyzed.
  • The results indicated that the percentage of patients with leucocytopenia, anemia and thrombocytopenia were 42.9%, 81% and 81% respectively at the time of diagnosis.
  • 52.4% of M(6) patients transferred to RAEB/RAEB-T and AML-M(2) subtype in the disease progression.
  • 11/19 cases (57.4%) achieved remission (CR 10; PR 1) after chemotherapy.
  • The median survival length of M(6) and MDS-->M(6) from time of diagnosis were 13.0 +/- 13.2 and 2.3 +/- 1.3 months respectively.
  • Most of M(6) patients would rather be classified MDS RAEB and RAEB-t with over-hyperplasia of erythron lineage than a subtype of AML.


25. Lundberg LG, Hellström-Lindberg E, Kanter-Lewensohn L, Lerner R, Palmblad J: Angiogenesis in relation to clinical stage, apoptosis and prognostic score in myelodysplastic syndromes. Leuk Res; 2006 Mar;30(3):247-53
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  • [Title] Angiogenesis in relation to clinical stage, apoptosis and prognostic score in myelodysplastic syndromes.
  • The International Prognostic Scoring System (IPSS), based on the number of cytopenias, percentage of bone marrow blasts and cytogenetics, is an important prognostic tool for patients with myelodysplastic syndrome (MDS).
  • In addition, factors such as high bone marrow cellularity and lactate dehydrogenase levels have been associated with an adverse outcome, spontaneously and after chemotherapy.
  • To assess the prognostic role of MVD in MDS, a cohort of 56 patients, thoroughly investigated for various clinical and morphological parameters, were followed-up for survival > or =60 months after the diagnostic analysis.
  • The highest median MVD value was observed in the RAEB group, but there was no overall significant difference between the FAB groups.
  • No significant correlations were observed between MVD and peripheral blood counts, bone marrow cellularity, percentage of bone marrow blasts and CD34 positive cells, apoptotic index (TUNEL), proliferation index (MIB-1), erythroid index, FAB group and IPSS score.
  • In contrast, bone marrow blast count <5%, low or normal cellularity, as well as a high erythroid index, indicated a favorable survival.
  • [MeSH-major] Apoptosis. Blast Crisis / pathology. Bone Marrow / pathology. Myelodysplastic Syndromes / pathology. Neovascularization, Pathologic / pathology
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Antigens, CD34 / blood. Blood Cell Count. Cell Proliferation. Cohort Studies. Disease-Free Survival. Erythrocyte Indices. Female. Humans. In Situ Nick-End Labeling. Male. Middle Aged. Predictive Value of Tests. Prognosis. Risk Factors


26. Vaena DA, Walker P, Pennington K, Stephens A, Stender MJ, Yiannoutsos CT, Young C, Stoner C, Cripe LD, Hoosier Oncology Group: Phase II study of low-dose topotecan in myelodysplastic syndromes: a Hoosier Oncology Group (HOG) study. Leuk Res; 2004 Jan;28(1):49-52
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  • [Title] Phase II study of low-dose topotecan in myelodysplastic syndromes: a Hoosier Oncology Group (HOG) study.
  • Therefore, we studied topotecan 1.5mg/m2 per day i.v. over 2 h for three consecutive days in 20 patients with high-risk MDS (12 RAEB; 4 RAEB-T; 4 CMMoL).
  • There were three deaths within the first cycle of therapy.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Enzyme Inhibitors / administration & dosage. Myelodysplastic Syndromes / drug therapy. Topotecan / administration & dosage
  • [MeSH-minor] Aged. Aged, 80 and over. Anemia, Refractory, with Excess of Blasts / diagnosis. Anemia, Refractory, with Excess of Blasts / drug therapy. Drug Administration Schedule. Humans. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Middle Aged. Remission Induction. Treatment Outcome


27. Martino R, Valcárcel D, Brunet S, Sureda A, Sierra J: Comparable non-relapse mortality and survival after HLA-identical sibling blood stem cell transplantation with reduced or conventional-intensity preparative regimens for high-risk myelodysplasia or acute myeloid leukemia in first remission. Bone Marrow Transplant; 2008 Jan;41(1):33-8
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  • [Title] Comparable non-relapse mortality and survival after HLA-identical sibling blood stem cell transplantation with reduced or conventional-intensity preparative regimens for high-risk myelodysplasia or acute myeloid leukemia in first remission.
  • We prospectively compared two strategies of allogeneic PBSCT from HLA-identical siblings in adults with poor-risk AML or myelodysplastic syndrome with >5% marrow blasts in an early disease status (AML or refractory anemia with excess blasts (RAEB type 2) in first remission after chemotherapy or untreated RAEB type 1).
  • [MeSH-major] Hematopoietic Stem Cell Transplantation / mortality. Histocompatibility Testing. Leukemia, Myeloid, Acute / therapy. Myelodysplastic Syndromes / therapy. Transplantation Conditioning


28. 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.
  • Acute leukaemias in relapse after allogeneic stem cell transplantation (SCT) respond poorly to donor leucocyte infusions (DLI) compared with chronic myeloid leukaemia (CML), at least in part because of faster disease kinetics.
  • 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.
  • Donors were fully human leucocyte antigen (HLA) -matched in 13 cases with a single class A mismatch in one.
  • Actuarial overall survival was 60% and disease-free survival was 26% at 58 months.
  • Transplants were well tolerated with no treatment-related deaths.
  • The major complication was graft-versus-host disease (GvHD, acute >/= grade II-2 cases, chronic - eight cases, two limited, six extensive) although there have been no deaths attributable to this.
  • 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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29. 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.
  • 3-year expected OS in no aGVHD,grade I - II aGVHD and grade III - IV aGVHD group was 57.75% , 100% and 0% , respectively (P = 0.009).
  • 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.


30. Horikoshi M, Machida U, Itikawa M, Seo S, Masuda S, Kurokawa M, Ogawa S, Sunaga S, Honda H, Aoki K, Chiba S, Mitani K, Hirai H, Yazaki Y: [Essential thrombocythemia in transformation from myelodysplastic syndrome to acute myeloid leukemia with inv(3) after treatment for gastric cancer]. Rinsho Ketsueki; 2000 Jan;41(1):68-71
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  • [Title] [Essential thrombocythemia in transformation from myelodysplastic syndrome to acute myeloid leukemia with inv(3) after treatment for gastric cancer].
  • In March 1990, a 61-year-old man was given a diagnosis of essential thrombocythemia with a normal karyotype and subsequently treated with hydroxyurea.
  • Refractory anemia with excess of blasts in transformation and chromosomal abnormalities including -5, -7, 20q-developed in August 1998.
  • Combined chemotherapy with daunorubicin, cytarabine, mercaptopurine, and prednisolone, had only limited effectiveness.
  • Acute myeloid leukemia was finally diagnosed in October 1998, and chromosomal analysis disclosed inv(3) in addition to -5 and -7.
  • The appearance of inv(3) might be related to leukemic transformation of hematopoietic stem cell disease with an increase in the number of megakaryocytes and platelets.
  • [MeSH-major] Chromosome Inversion. Chromosomes, Human, Pair 3 / genetics. Leukemia, Myeloid, Acute / pathology. Myelodysplastic Syndromes / pathology. Neoplasms, Second Primary. Stomach Neoplasms. Thrombocythemia, Essential / complications
  • [MeSH-minor] Aged. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Fatal Outcome. Gastrectomy. Humans. Hydroxyurea / therapeutic use. Karyotyping. Male. Tegafur / administration & dosage. Uracil / administration & dosage


31. Roboz GJ, Knovich MA, Bayer RL, Schuster MW, Seiter K, Powell BL, Woodruff RD, Silver RT, Frankel AE, Feldman EJ: Efficacy and safety of gemtuzumab ozogamicin in patients with poor-prognosis acute myeloid leukemia. Leuk Lymphoma; 2002 Oct;43(10):1951-5
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  • [Title] Efficacy and safety of gemtuzumab ozogamicin in patients with poor-prognosis acute myeloid leukemia.
  • The objective of this work was to determine the safety and efficacy of gemtuzumab ozogamicin in patients with poor prognosis acute myeloid leukemia (AML).
  • (2) AML refractory to chemotherapy at initial induction or at first relapse;.
  • (4) myeloid blast crisis of chronic myeloid leukemia (CML);.
  • (5) untreated patients > or = 70 years or > or = 55 years with abnormal cytogenetics (excluding inv 16, t(15;17) and t(8;21)) and/or an antecedent hematologic disorder;.
  • (6) refractory anemia with excess blasts in transformation (RAEBT).
  • Forty-three patients, ages 19-84 (mean 62), were treated, including 7 patients with untreated AML age > 70 years, 2 with untreated RAEBT, 14 with AML first salvage (first remission 0-6 months), 15 with AML > or = second salvage and 14 with myeloid blast phase of CML.
  • In conclusion, in patients with relapsed/refractory AML, gemtuzumab ozogamicin has a comparable response rate to single-agent chemotherapy and may offer a more favorable toxicity profile.
  • [MeSH-major] Aminoglycosides. Anti-Bacterial Agents / administration & dosage. Antibodies, Monoclonal / administration & dosage. Leukemia, Myeloid / drug therapy
  • [MeSH-minor] Acute Disease. Adult. Aged. Aged, 80 and over. Antibodies, Monoclonal, Humanized. Female. Humans. Male. Middle Aged. Prognosis. Remission Induction. Risk Assessment. Salvage Therapy. Treatment Outcome

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  • (PMID = 12481890.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Aminoglycosides; 0 / Anti-Bacterial Agents; 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / gemtuzumab
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32. Beran M: Intensive chemotherapy for patients with high-risk myelodysplastic syndrome. Int J Hematol; 2000 Aug;72(2):139-50
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  • [Title] Intensive chemotherapy for patients with high-risk myelodysplastic syndrome.
  • Standard antileukemic chemotherapy induces complete remission in approximately half of patients with high-risk (HR) myelodysplastic syndrome (MDS).
  • Intensification of induction therapy by the use of intermediate- or high-dose cytosine arabinoside in combination with fludarabine, idarubicin, or topotecan seemingly improved complete response (CR) rates, particularly in patients with poor prognosis karyotypes.
  • Regardless of the intensity of chemotherapy, remissions are short, even with continuation of intensive postremission therapy.
  • Long-term disease-free survival remains dismal.
  • In a large population with HR MDS treated with high-dose chemotherapy, only 5% of patients were alive at 3 years, and a majority of survivors were the younger patients with diploid karyotype refractory anemia with excess blasts in transformation.
  • Further intensification of either induction chemotherapy or postremission therapy is unlikely to improve results with current drug combinations.
  • With these results at hand, the role of intensive chemotherapy in the management of MDS remains controversial.
  • Because CR status is associated with clinical benefits and possibly better survival, induction of CR should remain an important aim for HR MDS.
  • The intensive combination chemotherapy may be integrated as an initial part of the management of HR MDS, as an alternative for patients not eligible for allogeneic bone marrow transplantation (BMT).
  • Postremission therapy remains a major challenge.
  • It should involve either allogeneic BMT or investigational approaches to eliminate or control the minimal residual disease with different mechanisms In elderly patients, allogeneic "minitransplant" is an investigational alternative seeking to exploit graft-versus-tumor reaction.
  • New agents, such as farnesyl transferase inhibitors (ras inhibitors), drug-antibody conjugates (Myelotarg), thalidomide, arsenic trioxide, maintenance chemotherapy with hypomethylating agents, or oral topoisomerase inhibitors along with agents modulating factors affecting growth and differentiation, should be explored to maintain remission with minimal compromise of quality of life.
  • Although prognostic scoring systems such as the new International Prognostic Scoring System (IPSS) do not predict for initial response, IPSS continues to predict survival in patients treated with high-dose chemotherapy.
  • Although activity of new agents could be rapidly assessed in single-arm pilot studies, the final merit of high-dose chemotherapy could be assessed only in well-designed randomized trials with patients assigned according to risk-based classification and evaluated for response by generally accepted and standardized criteria.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Myelodysplastic Syndromes / therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Humans. Middle Aged. Remission Induction. Risk Factors. Treatment Outcome


33. Ferrero D, Darbesio A, Giai V, Genuardi M, Dellacasa CM, Sorasio R, Bertini M, Boccadoro M: Efficacy of a combination of human recombinant erythropoietin + 13-cis-retinoic acid and dihydroxylated vitamin D3 to improve moderate to severe anaemia in low/intermediate risk myelodysplastic syndromes. Br J Haematol; 2009 Feb;144(3):342-9
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  • [Title] Efficacy of a combination of human recombinant erythropoietin + 13-cis-retinoic acid and dihydroxylated vitamin D3 to improve moderate to severe anaemia in low/intermediate risk myelodysplastic syndromes.
  • The efficacy of human recombinant erythropoietin (rEPO) in myelodysplastic syndromes (MDS) has generally been best in untransfused patients with 'refractory anaemia' according to the World Health Organization (WHO).
  • We treated 63 MDS patients [excluding refractory anaemia with excess blasts, type 2 (RAEB2)] with a previously tested combination of 13-cis-retinoic acid and dihydroxylated vitamin D3 +/- 6-thioguanine in addition to rEPO.
  • Most patients were categorized as refractory cytopenia with multilineage dysplasia and RAEB1, with intermediate 1 International Prognostic Scoring System (IPSS) score; all had Hb <95 g/l, and 70% required regular erythrocyte transfusions.
  • Treatment was well tolerated, and erythroid response rate according to new International Working Group criteria was 60%: 50% in RAEB1 and 64% in non-RAEB patients (P = 0.383).
  • Median survival reached 14 months for RAEB1 and 55 months for non-RAEB patients, with a significant difference in the latter between responders and non-responders (median 82 months vs. 44 months; P = 0.036).
  • Our combined therapy, independent of rEPO dosage, achieved in patients with unfavourable response predictors, a rate of anaemia improvement comparable to the best obtained in lower risk patients by high-dose rEPO.
  • [MeSH-major] Anemia / drug therapy. Calcitriol / therapeutic use. Erythropoietin / therapeutic use. Isotretinoin / therapeutic use. Myelodysplastic Syndromes / drug therapy. Vitamins / therapeutic use
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Drug Therapy, Combination. Female. Humans. Kaplan-Meier Estimate. Male. Middle Aged. Recombinant Proteins. Risk. Survival Rate. Treatment Outcome


34. Guan M, Chen SC, Ge CW: [Long-term effects of androgen combined with low dose all-trans-retinoic acid on myelodysplastic syndrome: follow-up of 60 cases]. Zhonghua Yi Xue Za Zhi; 2009 Apr 7;89(13):919-22
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  • METHODS: Sixty-two MDS patients, 48 with RA, 2 of RAS, 9 with RA with excess of blasts (RAEB), 2 with RAEB-transformation (RAEB-t ), and 1 with chronic myelogenous-monocytic leukemia (CMML) according to the FAB subtype standard, received stanazolol (6 mg/d) or danazol (600 mg/d) and low dose all-trans-retinoic acid (ATRA 10 mg/d).
  • Three months later the treatment was discontinued on 22 patients that showed ineffective and 2 more patients withdrew from the treatment due to exacerbation.
  • The remaining 36 patients were treated according to the original protocol, and the doses of these 2 drugs were reduced by half until the condition was exacerbated.
  • RESULTS: After 6 months of treatment, complete remission (CR) was seen in 1 patient, partial remission (PR) in 6 patients, and hematologic Improvement (HI) in 19 of the 60 patients evaluated with a response rate of 43.3% (26/60) in all patients, 50% (24/48) in RA/RAS group, and 16.7% (2/12) in RAEB/RAEB-t/CMML group.
  • There were not significant differences in cellularity, dysplastic hematopoiesis, and myeloblast before and after treatment among the RA/RAS patients.
  • After 12 months of treatment, CR was seen in 1 patient, PR in 7, and HI in 9, with a response rate of 28.3% (17/60) in all patients, 35.4% (17/48) in the RA/RAS group, and 0% (0/12) in the RAEB/RAEB-t/CMML group.
  • Adverse effects were mild and did not require discontinuance of the therapy.
  • The survival time of the 19 patients in the RA group that responded well to treatment was 54 months (41, 66), significantly longer than that of the 20 patients without good outcomes [23 months (13,32), chi2=4.72, P=0.025].
  • CONCLUSION: Effective, economic, and safe, stanozolol or danazol with low-dose all-trans-retinoic acid improves the life quality and prolongs the survival time of the MDS patients who respond well.
  • [MeSH-major] Androgens / therapeutic use. Myelodysplastic Syndromes / drug therapy. Tretinoin / therapeutic use
  • [MeSH-minor] Adolescent. Adult. Aged. Aged, 80 and over. Drug Therapy, Combination. Follow-Up Studies. Humans. Middle Aged. Time. Treatment Outcome. Young Adult


35. McManus PM: Classification of myeloid neoplasms: a comparative review. Vet Clin Pathol; 2005 Sep;34(3):189-212
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  • WHO revisions lower the blast threshold from 30% to 20% for diagnosing acute myeloid leukemia (AML) and expand and redefine AML categories.
  • 1) AML with recurrent genetic abnormalities, 2) AML with multilineage dysplasia, 3) AML with previous chemotherapy and/or radiation, and 4) AML, not otherwise categorized.
  • The lower blast percentage eliminates one category of myelodysplastic syndrome (MDS): refractory anemia with excess blasts in transformation.
  • A new MDS category was created: refractory cytopenia with multilineage dysplasia (RCMD), with lineage dysplasia assessed using newly defined percentage limits.
  • At least 10% of cells from each of 2 lineages must display atypia for a diagnosis of RCMD.
  • Chronic myelomonocytic leukemia has been removed from the MDS category and included in a new category of diseases that have features of both MDS and chronic leukemia.
  • WHO revisions are a signal to veterinary clinical pathologists to assess the validity of our system, which was built on premises now questioned.


36. Kuendgen A, Knipp S, Fox F, Strupp C, Hildebrandt B, Steidl C, Germing U, Haas R, Gattermann N: Results of a phase 2 study of valproic acid alone or in combination with all-trans retinoic acid in 75 patients with myelodysplastic syndrome and relapsed or refractory acute myeloid leukemia. Ann Hematol; 2005 Dec;84 Suppl 1:61-6
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Results of a phase 2 study of valproic acid alone or in combination with all-trans retinoic acid in 75 patients with myelodysplastic syndrome and relapsed or refractory acute myeloid leukemia.
  • Valproic acid (VPA) inhibits histone deacetylase activity and induces differentiation of acute myeloid leukemia (AML) blasts in vitro.
  • We observed clinical responses to VPA in patients with myelodysplastic syndrome (MDS) and AML.
  • Median treatment duration was 4 months for VPA and 2 months for ATRA.
  • Response rates were strongly dependent on disease type according to WHO classification.
  • We found a response rate of 52% in MDS patients with a normal blast count (refractory sideroblastic anemia, refractory cytopenia with multilineage dysplasia, and refractory sideroblastic cytopenia with multilineage dysplasia).
  • The response rate was 6% in refractory anemia with excess blasts (I + II), 16% in AML, and 0% in chronic myelomonocytic leukemia.
  • Bone marrow blast count was the only variable that predicted responses.
  • For patients with high-risk MDS, VPA may be combined with chemotherapy or demethylating drugs.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Histone Deacetylase Inhibitors. Leukemia, Myeloid / drug therapy. Myelodysplastic Syndromes / drug therapy. Valproic Acid / therapeutic use
  • [MeSH-minor] Acute Disease. Adult. Aged. Aged, 80 and over. Cell Differentiation / drug effects. Female. Histone Deacetylases / drug effects. Humans. Kaplan-Meier Estimate. Male. Middle Aged. Remission Induction. Treatment Outcome. Tretinoin / administration & dosage


37. Zhou FL, Zhang WG, Cao XM, Chen YX, He AL, Liu J, Zhao WH, Ma XR, Chen G: [Retrospective observation of curative effects on MDS refractory anemia with combination of all-trans retinoic acid, 1, 25-dihydroxyvitamin D3 and androgen]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2005 Oct;13(5):861-6
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [Retrospective observation of curative effects on MDS refractory anemia with combination of all-trans retinoic acid, 1, 25-dihydroxyvitamin D3 and androgen].
  • This study was aimed to examine whether a combination of all-trans retinoic acid (ATRA), 1, 25-dihydroxyvitamin D(3) and androgen possesses the therapeutic value for the MDS-refractory anemia (MDS-RA), and to analyze the mechanisms in detail.
  • The remaining 33 cases (group B) were provided with vitamin supplementation, chalybeate drugs, and one or two of the combination.
  • The further treatment for 16 out of 62 patients (25.81%), 13 failures (10 deaths, 2 RAEB and 1 RAEB-T) and 3 transformations (M(2), M(3), M(5)) with a median survival interval of 26.25 months, were observed and interrupted for some reasons.
  • Furthermore, the disease progression was observed in 12 out of 33 patients (36.36%) with a median survival interval of 16 months, 9 failures (including 6 deaths, 2 RAEB and 1 RAEB-T) and 3 transformations (M(2), M(3), M(4)).
  • The following requirements, if were met, would be significant for prognosis: the combination regiment, no transformation, children, no complication, female, 90-120 g/L of hemoglobin concentration, normal cellular bone marrow and uni-cytopenias (P < 0.05).
  • Moreover, Cox regression showed that therapy, transformation and age are all the independent factors (P < 0.05).
  • It is concluded that the combination of above mentioned 3 drugs may be effective and safe treatment for the patients with MDS-RA.
  • Its relevant mechanisms can be involved in the combination, that elicits a wide range of pharmacological effects, such as differentiation, anti-tumor-promotion, anti-apoptosis, anti-angiogenesis, anti-cachexia and immunoregulation.


38. Fukuda N, Shinohara K, Ota I, Muraki K, Shimohakamada Y: Therapy-related myelodysplastic syndrome in a case of cutaneous adult T-cell lymphoma. Int J Hematol; 2002 Jan;75(1):67-71
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  • [Title] Therapy-related myelodysplastic syndrome in a case of cutaneous adult T-cell lymphoma.
  • We report a case of therapy-related myelodysplastic syndrome (t-MDS) in adult T-cell lymphoma.
  • A 69-year-old man suffered from cutaneous adult T-cell lymphoma, which was treated with radiation to the skin and combination chemotherapy of CHOP-V-MMV and VEPA-B.
  • After 14 months of these therapies, anemia and thrombocytopenia appeared, and bone marrow aspiration smears showed immature myeloblasts, dysplastic erythroblasts, and micromegakaryocytes.
  • Therapy-related MDS of refractory anemia with an excess of blasts was diagnosed.
  • The patient died of pneumonia 21 months after diagnosis of cutaneous adult T-cell lymphoma.
  • [MeSH-major] Anemia, Refractory, with Excess of Blasts / etiology. Antineoplastic Combined Chemotherapy Protocols / adverse effects. Lymphoma, T-Cell, Cutaneous / complications. Radiotherapy / adverse effects
  • [MeSH-minor] Acute Disease. Aged. Bleomycin / administration & dosage. Bleomycin / adverse effects. Chromosome Aberrations. Combined Modality Therapy. Cyclophosphamide / administration & dosage. Cyclophosphamide / adverse effects. Disease Progression. Doxorubicin / administration & dosage. Doxorubicin / adverse effects. Doxorubicin / analogs & derivatives. Etoposide / administration & dosage. Etoposide / adverse effects. Fatal Outcome. HTLV-I Infections / complications. Human T-lymphotropic virus 1 / isolation & purification. Humans. Japan. Leukemia, Myeloid / complications. Leukemia-Lymphoma, Adult T-Cell / complications. Male. Nitrosourea Compounds / administration & dosage. Nitrosourea Compounds / adverse effects. Prednisolone / administration & dosage. Prednisolone / adverse effects. Proviruses / isolation & purification. Remission Induction. Translocation, Genetic. Vincristine / administration & dosage. Vincristine / adverse effects


39. Khalifa M, Laatiri MA, Chehata S, Rhaiem K, Gharbi O, Amama W, Ennabli S: [Adult primary myelodysplastic syndromes. Report of 36 cases]. Tunis Med; 2003 Apr;81(4):226-9
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  • [Transliterated title] Syndromes myelodysplasiques primitifs de l'adulte. A propos de 36 cas.
  • Eighty one per cent of patients were presented symptoms of anemia.
  • Hemogram showed anemia, leucopenia and thrombocytopenia respectively in 97%, 44% and 55% of cases.
  • Refractory anemia with excess blasts (AREB) is the most frequent FAB subtypes of MDS (17 cases).
  • Seventeen patients have received a chemotherapy.
  • At the time, the only curative treatment is the bone marrow transplantation, which is proposed to young patients with HLA identical donor.
  • [MeSH-major] Anemia, Refractory, with Excess of Blasts / etiology. Myelodysplastic Syndromes / diagnosis


40. Suzuki S, Hashino S, Yoshida S, Chiba K, Izumiyama K, Kurosawa M, Musashi M, Asaka M: del11(p11-13) with overexpression of Wilms' tumor gene during leukemic transformation of myelodysplastic syndrome. Ann Hematol; 2002 Oct;81(10):605-8
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  • We report a case of leukemic transformation from myelodysplastic syndrome (MDS) with a sole chromosome abnormality of del11(p11-13).
  • The patient had been diagnosed as having MDS (refractory anemia with excess of blast cells, RAEB) in May 1998.
  • At that time, cytogenetic analysis of bone marrow cells showed a normal karyotype.
  • The patient received sequential chemotherapy with low-dose cytosine arabinoside (AraC) and macrophage colony-stimulating factor (M-CSF).
  • Complete remission was obtained with this treatment, but the disease gradually progressed after June 1999.
  • Cytogenetical analysis showed del11(p11-13) in 6 of 40 cells analyzed at that time, and the disease had evoluted to overt leukemia in December 1999 with a gradual increase in the abnormal clone.
  • Furthermore, mRNA of the WT1 gene located at chromosome 11p13 was overexpressed during leukemic transformation, whereas it was not detected at the time of the initial diagnosis of MDS (RAEB) in May 1998.
  • [MeSH-major] Cell Transformation, Neoplastic / genetics. Chromosome Deletion. Chromosomes, Human, Pair 11. Genes, Wilms Tumor. Leukemia / genetics. Myelodysplastic Syndromes / pathology
  • [MeSH-minor] Blast Crisis / genetics. Humans. Male. Middle Aged. RNA, Messenger / metabolism


41. Kim MK, Lee JL, Cho HS, Bae SH, Ryoo HM, Lee KH, Hyun MS: The hematologic response to anti-apoptotic cytokine therapy: results of pentoxifylline, ciprofloxacin, and dexamethasone treatment for patients with myelodysplastic syndrome. J Korean Med Sci; 2006 Feb;21(1):40-5
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  • [Title] The hematologic response to anti-apoptotic cytokine therapy: results of pentoxifylline, ciprofloxacin, and dexamethasone treatment for patients with myelodysplastic syndrome.
  • The combination of pentoxifylline (P) and ciprofloxacin (C) has been shown to reduce the serum levels of TNF-alpha, and an earlier trial of P and C with dexamethasone (D) provided good palliation for patients with MDS.
  • The purpose of this study is to assess the hematologic response to PCD therapy for patients suffering with MDS.
  • 21 of 25 patients who completed at least of 12 weeks of treatment were evaluable for the treatment efficacy.
  • The diagnoses according to WHO classification included: RA (n=5), RCMD (n=10), RARS (n=1), RCMD/RS (n=1), RAEB (3), and CMML (n=1).
  • The median time to response was 4 weeks (range: 2-12 weeks), and it is interesting that 9 of 11 patients who had a response remained without relapse for a median of 177 days (range: 78-634 days).
  • These preliminary results indicate that anti-cytokine therapy with PCD is an effective and well tolerated palliative treatment for patients with MDS.
  • [MeSH-major] Apoptosis / drug effects. Myelodysplastic Syndromes / blood. Tumor Necrosis Factor-alpha / metabolism
  • [MeSH-minor] Adolescent. Adult. Aged. Anti-Infective Agents / adverse effects. Anti-Infective Agents / therapeutic use. Anti-Inflammatory Agents / adverse effects. Anti-Inflammatory Agents / therapeutic use. Ciprofloxacin / adverse effects. Ciprofloxacin / therapeutic use. Dexamethasone / adverse effects. Dexamethasone / therapeutic use. Drug Therapy, Combination. Erythrocyte Count. Female. Hematologic Agents / adverse effects. Hematologic Agents / therapeutic use. Humans. Male. Middle Aged. Nausea / chemically induced. Pentoxifylline / adverse effects. Pentoxifylline / therapeutic use. Platelet Count. Time Factors. Treatment Outcome

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  • (PMID = 16479063.001).
  • [ISSN] 1011-8934
  • [Journal-full-title] Journal of Korean medical science
  • [ISO-abbreviation] J. Korean Med. Sci.
  • [Language] eng
  • [Publication-type] Clinical Trial; Comparative Study; Journal Article
  • [Publication-country] Korea (South)
  • [Chemical-registry-number] 0 / Anti-Infective Agents; 0 / Anti-Inflammatory Agents; 0 / Hematologic Agents; 0 / Tumor Necrosis Factor-alpha; 5E8K9I0O4U / Ciprofloxacin; 7S5I7G3JQL / Dexamethasone; SD6QCT3TSU / Pentoxifylline
  • [Other-IDs] NLM/ PMC2733976
  •  go-up   go-down


42. Mantovani L, Lentini G, Hentschel B, Wickramanayake PD, Loeffler M, Diehl V, Tesch H: Treatment of anaemia in myelodysplastic syndromes with prolonged administration of recombinant human granulocyte colony-stimulating factor and erythropoietin. Br J Haematol; 2000 May;109(2):367-75
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  • [Title] Treatment of anaemia in myelodysplastic syndromes with prolonged administration of recombinant human granulocyte colony-stimulating factor and erythropoietin.
  • Treatment with recombinant human erythropoietin (rhEPO) improves anaemia in approximately 20% of the patients with myelodysplastic syndromes (MDS).
  • Recent reports suggest that a combination treatment with rhEPO plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) given for up to 18 weeks may result in a higher erythroid response rate than with rhEPO alone.
  • We investigated the potential advantage of an even more prolonged schedule of combined rhG-CSF and rhEPO treatment to obtain and maintain stable responses.
  • In a phase II study, 33 patients with MDS [17 with refractory anaemia (RA), eight with RA with ringed sideroblasts (RARS), eight with RA with excess blasts (RAEB) with bone marrow blast counts less than 20%] were scheduled to receive at least 36 weeks of combined therapy with rhG-CSF and rhEPO.
  • Seventeen of 28 evaluable patients demonstrated an erythroid response [61%; 95% confidence interval (CI) 41-78] after 12 weeks of treatment.
  • Seven of these responses developed between week 12 and week 36, whereas two initially responding patients became refractory.
  • The cytokine therapy was generally well tolerated.
  • After 1 year and 2 years of continuous combined treatment, 50% of the initially included patients showed a continuing response.
  • Our results suggest that a prolonged combination treatment with rhG-CSF and rhEPO is highly effective in achieving a stable and long-lasting erythroid response in many patients with MDS and low blast count.
  • [MeSH-major] Anemia / drug therapy. Erythropoietin / administration & dosage. Granulocyte Colony-Stimulating Factor / administration & dosage. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Disease-Free Survival. Drug Administration Schedule. Drug Therapy, Combination. Erythrocyte Count. Female. Humans. Male. Middle Aged. Recombinant Proteins. Time Factors. Treatment Outcome


43. Stavroyianni N, Yataganas X, Abazis D, Pangalos C, Meletis J: Acute promyelocytic leukemia relapsing into FAB-M2 acute myeloid leukemia with trisomy 8. Cancer Genet Cytogenet; 2000 Feb;117(1):82-3
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  • [Title] Acute promyelocytic leukemia relapsing into FAB-M2 acute myeloid leukemia with trisomy 8.
  • Acute promyelocytic leukemia was diagnosed in a 48-year-old man; the karyotype was normal, whereas reverse transcriptase polymerase chain reaction (RT-PCR) analysis identified PML/RAR alpha chimeric transcripts of the bcr3 type.
  • Rather unexpectedly, the patient did not respond to alltrans retinoic acid administration; he attained complete remission with conventional chemotherapy and became PML/RAR alpha negative.
  • Bone marrow examination was compatible with myelodysplasia of the RAEB type; the karyotype was normal.
  • Then, after 10 months, he developed overt acute myeloid leukemia with PML/RAR alpha negative, French-American-British M2 blasts; karyotypic analysis revealed mosaicism for trisomy 8.
  • [MeSH-major] Chromosomes, Human, Pair 8. Leukemia, Myeloid, Acute / genetics. Leukemia, Promyelocytic, Acute / pathology. Trisomy
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Humans. Male. Middle Aged. Recurrence. Reverse Transcriptase Polymerase Chain Reaction


44. Huebner G, Karthaus M, Pethig K, Freund M, Ganser A: Myelodysplastic syndrome and acute myelogenous leukemia secondary to heart transplantation. Transplantation; 2000 Aug 27;70(4):688-90
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  • [Title] Myelodysplastic syndrome and acute myelogenous leukemia secondary to heart transplantation.
  • Myelodysplastic syndrome and acute myelogenous leukemia secondary to radiotherapy, radiation exposure, and chemotherapy is a well-documented malignant stem cell disorder.
  • The incidence and natural course of myelodysplastic syndrome and acute myelogenous leukemia after organ transplantation remains less thoroughly investigated.
  • We report five patients (age, 22-63 years) with myelodysplastic syndrome (MDS) (n=1) or acute myelogenous leukemia (AML) (n=4) occuring 4-8 years after transplantation.
  • Immunosuppression consisted uniformly of a combination of prednisone, cyclosporine, and azathioprine.
  • One patient with MDS, refractory anemia with excess of blasts according to the FAB criteria, is alive with transfusion dependency 32 months after diagnosis.
  • Treatment results are poor in this subgroup of patients with secondary leukemia.
  • [MeSH-major] Cardiomyopathy, Dilated / surgery. Heart Failure / surgery. Heart Transplantation. Leukemia, Myeloid, Acute / etiology. Myelodysplastic Syndromes / etiology. Postoperative Complications
  • [MeSH-minor] Adult. Chromosome Aberrations. Drug Therapy, Combination. Female. Humans. Immunosuppressive Agents / therapeutic use. Karyotyping. Male. Middle Aged


45. Maciejewski JP, Risitano AM, Sloand EM, Wisch L, Geller N, Barrett JA, Young NS: A pilot study of the recombinant soluble human tumour necrosis factor receptor (p75)-Fc fusion protein in patients with myelodysplastic syndrome. Br J Haematol; 2002 Apr;117(1):119-26
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  • We determined spontaneous TNF-alpha production by marrow cells in MDS; TNF-alpha production was elevated (> mean + 2 x SD of controls) in > 1/3 of patients, but did not correlate with clinical parameters.
  • The drug was well tolerated and 15 patients were evaluable.
  • Progression to refractory anaemia with excess blasts in transformation (RAEBt) or leukaemia was observed in three patients.
  • Although anti-TNF therapy with Enbrel was well tolerated at the dosages used in MDS, its efficacy as a single agent appears low.
  • [MeSH-major] Immunoglobulin G / therapeutic use. Myelodysplastic Syndromes / drug therapy. Receptors, Tumor Necrosis Factor / therapeutic use. Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • [MeSH-minor] Adult. Aged. Anemia, Refractory / drug therapy. Anemia, Refractory / therapy. Anemia, Refractory, with Excess of Blasts / drug therapy. Anemia, Refractory, with Excess of Blasts / therapy. Blood Transfusion. Bone Marrow Cells / immunology. Colony-Forming Units Assay. Etanercept. Humans. Middle Aged. Pilot Projects. Treatment Failure


46. Platzbecker U, Haase M, Herbst R, Hänel A, Voigtmann K, Thiede CH, Mohr B, Schleyer E, Leopold T, Orth M, Hänel M, Ehninger G, Bornhäuser M: Activity of sirolimus in patients with myelodysplastic syndrome--results of a pilot study. Br J Haematol; 2005 Mar;128(5):625-30
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  • [Title] Activity of sirolimus in patients with myelodysplastic syndrome--results of a pilot study.
  • Increasing data suggest that sirolimus might affect these pathways positively, thus being of possible therapeutic benefit in patients with this disease.
  • Nineteen patients (n = 19) with a median age of 72 years (range 54-80 years) diagnosed with MDS received sirolimus orally with a target blood concentration of 3-12 ng/ml.
  • Three patients [1 x refractory anaemia with excess blasts (RAEB)-2, 1 x RAEB-1, 1 x refractory cytopenia with multilineage dysplasia] showed either a major (1 x platelet, 1 x neutrophil) or a minor (1 x erythroid, 2 x platelet) haematological response according to International Working Group criteria.
  • [MeSH-major] Immunosuppressive Agents / administration & dosage. Myelodysplastic Syndromes / drug therapy. Sirolimus / administration & dosage
  • [MeSH-minor] Administration, Oral. Aged. Aged, 80 and over. Anemia, Refractory, with Excess of Blasts / blood. Anemia, Refractory, with Excess of Blasts / drug therapy. Erythrocyte Count. Female. Humans. Leukocyte Count. Male. Middle Aged. Pilot Projects. Platelet Count. Treatment Outcome


47. Ribrag V, Suzan F, Ravoet C, Feremans W, Guerci A, Dreyfus F, Damaj G, Vantelon JM, Bourhis JH, Fenaux P: Phase II trial of CPT-11 in myelodysplastic syndromes with excess of marrow blasts. Leukemia; 2003 Feb;17(2):319-22
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  • [Title] Phase II trial of CPT-11 in myelodysplastic syndromes with excess of marrow blasts.
  • We conducted a phase II trial of CPT-11 in 26 patients with high-risk MDS (RAEB 1: n = 4; RAEB 2: n = 9; MDS having progressed to AML: n = 10; CMML: n = 3) who could not receive anthracycline/cytarabine intensive chemotherapy.
  • Induction therapy consisted of four courses of CPT-11 given intravenously at 200 mg/m(2) every 2 weeks.
  • Patient characteristics were: median age, 71 (range 51-77); sex, (M/F), 21/5, median % marrow blasts cells, 13.5 (range 7-52).
  • Six patients stopped treatment after only one or two courses of CPT-11 due to severe infection (n = 2), progressive disease (n = 3), acute lysis syndrome with renal failure (n = 1).
  • Thus CPT-11 has an interesting activity in MDS with excess of blasts; toxicity is easily managed and most patients can be treated in the out-clinic setting.
  • [MeSH-major] Anemia, Refractory, with Excess of Blasts / drug therapy. Antineoplastic Agents, Phytogenic / therapeutic use. Bone Marrow / pathology. Camptothecin / analogs & derivatives. Camptothecin / therapeutic use. Myelodysplastic Syndromes / drug therapy. Myelodysplastic Syndromes / pathology
  • [MeSH-minor] Aged. Blast Crisis. Disease Progression. Female. Humans. Infusions, Intravenous. Leukemia, Myeloid, Acute. Male. Middle Aged. Survival Analysis. Time Factors


48. Fenaux P: Inhibitors of DNA methylation: beyond myelodysplastic syndromes. Nat Clin Pract Oncol; 2005 Dec;2 Suppl 1:S36-44
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  • DNA methyltransferase (DNMT) inhibitors, azacitidine (Vidaza, Pharmion, Boulder, CO, USA) and decitabine (Dacogen; SuperGen Inc, Dublin, CA, USA, and MGI Pharma Inc, Bloomington, MN, USA), have had a significant impact on the treatment paradigm of myelodysplastic syndromes (MDSs), previously managed mainly by supportive care and hematopoietic-stem-cell transplantation.
  • The positive clinical experience seen in MDS to date coupled with the persistent challenges faced in the treatment of other hematologic malignancies has served as the impetus for further exploration of the therapeutic value of DNMT inhibitors beyond MDS.
  • In that respect, the majority of data for these agents are in the setting of acute myelogenous leukemia (AML).
  • Experience with these agents in patients with refractory anemia with excess blasts in transformation (reclassified by the World Health Organization as AML) was also reported in the clinical trials submitted to the FDA for approval of azacitidine for MDS.
  • Some use has also been described in chronic myelogenous leukemia and acute lymphocytic leukemia.
  • Further studies are needed to clarify the appropriate dose and the number and duration of cycles in the treatment of leukemias, and to identify ideal candidates for therapy, explore the role of DNMT inhibitors in combination with other agents, especially histone deacetylase inhibitors, delineate differences between the commercially available agents, and establish the long-term safety of these agents.
  • To this end, experience with DNMT inhibitors in hematologic malignancies other than MDS is reviewed in an effort to better understand the therapeutic potential of these agents and to define areas of future exploration in these settings.
  • [MeSH-major] Antimetabolites, Antineoplastic / therapeutic use. Azacitidine / analogs & derivatives. Azacitidine / therapeutic use. DNA Modification Methylases / antagonists & inhibitors. Hematologic Neoplasms / drug therapy
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Humans. Leukemia / drug therapy. Leukemia / genetics

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  • (PMID = 16341239.001).
  • [ISSN] 1743-4254
  • [Journal-full-title] Nature clinical practice. Oncology
  • [ISO-abbreviation] Nat Clin Pract Oncol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 776B62CQ27 / decitabine; EC 2.1.1.- / DNA Modification Methylases; M801H13NRU / Azacitidine
  • [Number-of-references] 73
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49. Connell NT, Cassidy HM, Berz D, Winer ES: Alphabet soup: RAEB, HMA, DOE, and AFOP. Med Health R I; 2010 Dec;93(12):385-6
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Alphabet soup: RAEB, HMA, DOE, and AFOP.
  • [MeSH-major] Anemia, Refractory, with Excess of Blasts / drug therapy. Antimetabolites, Antineoplastic / therapeutic use. Cryptogenic Organizing Pneumonia / drug therapy. Glucocorticoids / therapeutic use. Heart Transplantation. Methylprednisolone / therapeutic use. Pulmonary Fibrosis / drug therapy
  • [MeSH-minor] Azacitidine / analogs & derivatives. Azacitidine / therapeutic use. Biopsy. Bronchoscopy. Diagnosis, Differential. Drug Therapy, Combination. Humans. Male. Middle Aged. Tomography, X-Ray Computed

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  • (PMID = 21214078.001).
  • [ISSN] 1086-5462
  • [Journal-full-title] Medicine and health, Rhode Island
  • [ISO-abbreviation] Med Health R I
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 0 / Glucocorticoids; 776B62CQ27 / decitabine; M801H13NRU / Azacitidine; X4W7ZR7023 / Methylprednisolone
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50. Cesaro S, Strugo L, Alaggio R, Cecchetto G, Rigobello L, Pillon M, Cusinato R, Zanesco L: Voriconazole for invasive aspergillosis in oncohematological patients: a single-center pediatric experience. Support Care Cancer; 2003 Nov;11(11):722-7
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  • Voriconazole is a new triazole active orally and parenterally that recently proved effective in the treatment of invasive aspergillosis and in empirical antifungal therapy for persistently febrile neutropenic patients.
  • We report our experience with voriconazole in seven children with invasive aspergillosis, i.e., four girls and three boys with a median age of 5 (range 2-13) years affected by acute lymphoblastic leukemia (3), acute myeloid leukemia (2), refractory anemia with excess of blasts (1), and severe aplastic anemia (1).
  • First-line therapy in all patients was liposomal amphotericin B (AmBisome) administered at a dosage of 3-5 mg/kg day.
  • The voriconazole treatment was well tolerated.
  • Three patients are alive and well 6, 5, and 4 months after the diagnosis of aspergillosis.
  • Voriconazole appears to be an effective salvage treatment for invasive aspergillosis in pediatric patients, with good responses in patients who recover from neutropenia or are not relapsing.
  • [MeSH-major] Antifungal Agents / administration & dosage. Aspergillosis / drug therapy. Aspergillosis / etiology. Hematologic Neoplasms / therapy. Pyrimidines / administration & dosage. Triazoles / administration & dosage
  • [MeSH-minor] Adolescent. Amphotericin B / administration & dosage. Anemia, Aplastic / drug therapy. Anemia, Refractory / drug therapy. Antineoplastic Agents / adverse effects. Bone Marrow Transplantation / adverse effects. Child. Child, Preschool. Dose-Response Relationship, Drug. Drug Administration Schedule. Female. Humans. Leukemia, Myelomonocytic, Acute / drug therapy. Male. Neutropenia / chemically induced. Neutropenia / complications. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Time Factors. Treatment Outcome. Voriconazole

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  • (PMID = 13680324.001).
  • [ISSN] 0941-4355
  • [Journal-full-title] Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
  • [ISO-abbreviation] Support Care Cancer
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antifungal Agents; 0 / Antineoplastic Agents; 0 / Pyrimidines; 0 / Triazoles; 7XU7A7DROE / Amphotericin B; JFU09I87TR / Voriconazole
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51. Kobbe G, Germing U, Aivado M, Zohren F, Schubert D, Strupp C, Pape H, Tenderich G, Körfer R, Storb R, Haas R, Schneider P: Treatment of secondary myelodysplastic syndrome after heart transplantation with chemotherapy and nonmyeloablative stem-cell transplantation. Transplantation; 2002 Oct 27;74(8):1198-200
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  • [Title] Treatment of secondary myelodysplastic syndrome after heart transplantation with chemotherapy and nonmyeloablative stem-cell transplantation.
  • BACKGROUND: Treatment of secondary cancer after solid-organ transplantation is difficult because of coexisting medical conditions, reduced organ function, or advanced age in most patients.
  • METHODS: A 60-year-old man developed treatment-related myelodysplastic syndrome (refractory anemia with excess blasts in transformation) 10 years after orthotopic heart transplantation.
  • After remission induction with chemotherapy, the patient received peripheral blood stem cells from his HLA-identical ABO-mismatched (A-->O) sister after conditioning with fludarabine and low-dose total-body irradiation (200 cGy).
  • Five months after transplant, the patient developed pure red cell aplasia that resolved after treatment.
  • CONCLUSIONS: Allogeneic blood stem-cell transplantation using minimal conditioning is a new, promising treatment option for patients with hematologic malignancies after solid-organ transplantation.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Heart Transplantation. Myelodysplastic Syndromes / drug therapy. Myelodysplastic Syndromes / etiology. Stem Cell Transplantation
  • [MeSH-minor] Antibiotics, Antineoplastic / administration & dosage. Antimetabolites, Antineoplastic / administration & dosage. Cytarabine / administration & dosage. Humans. Idarubicin / administration & dosage. Male. Middle Aged. Mitoxantrone / administration & dosage. Postoperative Complications / therapy


52. 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.
  • Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells characterized by ineffective and inadequate hematopoiesis.
  • 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.
  • Because MDS is a heterogeneous disorder, specific gene abnormalities playing a role in the myelodysplastic process have been difficult to identify.
  • Although point mutations of critical genes have been demonstrated to contribute to the development MDS, there was no strong correlation between these mutations and clinical features.
  • 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


53. Meng HT, Mai WY, Chen ZM, Lou JY, Jin J: [Cytogenetic and clinical analysis of -7/7q- abnormalities in acute leukemia and myelodysplastic syndrome]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2004 Aug;12(4):460-3
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  • [Title] [Cytogenetic and clinical analysis of -7/7q- abnormalities in acute leukemia and myelodysplastic syndrome].
  • The objective was to study the incidence and prognosis significance of -7/7q- abnormalities in acute leukemia and myelodysplastic syndrome.
  • Conventional cytogenetic analysis of R-band was used to test -7/7q- chromosome abnormalities in 410 patients with acute leukemia (AL), in 71 cases of myelodysplastic syndrome (MDS) and in 36 cases of chronic myelogenous leukemia in accelerated phase (CML-AP).
  • The -7/7q- abnormalities could be found in acute myeloblastic leukemia (AML) and acute lymphocytic leukemia (ALL), incidences of which were 4.70% and 6.25% (P > 0.05) respectively.
  • Monosomy -7 and 7q- abnormality clone was found in one patient with MDS-RAEB, and the number of cells with -7 abnormality was greater than that of 7q- abnormality cells.
  • Four patients acquired CR among 7 patients with ALL after chemotherapy, but 2 out of 13 patients with AML achieved CR while 6 out of 7 patients with MDS transformed into AL.


54. Xu S, Hu XM, Xu YG: [Effect of treatment for myelodysplastic syndrome by Qinghuang Powder combined with Chinese herbs for reinforcing shen and strenghening pi]. Zhongguo Zhong Xi Yi Jie He Za Zhi; 2008 Mar;28(3):216-8
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  • [Title] [Effect of treatment for myelodysplastic syndrome by Qinghuang Powder combined with Chinese herbs for reinforcing shen and strenghening pi].
  • OBJECTIVE: To observe the clinical efficacy of Qinghuang Powder combined with Chinese herbs for reinforcing Shen and strenghening Pi in treating myelodysplastic syndrome (MDS).
  • METHODS: fifty-five patients with diagnosis fitting to MDS were treated with Qinghuang Powder and decoction for strengthening Pi and reinforcing Shen, in combination with Stanozololum.
  • 5%) in the 34 patients of type RA/RAS were CR, with the total effective rate of 82.4% (28/34 cases), and in the 21 patients of type RAEB, 9.5% (2/21 cases) were CR with the total effective rate of 61.9% (13/21 cases), showing insignificant statistical difference between the two types (P > 0.05).
  • By international prognostic scoring system (IPSS), the treatment was evaluated as CR in 10 patients, effective in 25 and ineffective in 11 in 36 patients of moderate risk group I , the responding numbers were 1, 4, 2 in 7 patients of moderate risk group II and 0, 3, 3 in 6 patients of high risk group, respectively, also showing insignificant difference between groups (P > 0.05).
  • Levels of Hb, WBC and platelet significantly increased after treatment (P < 0. 05).
  • CONCLUSION: The comprehensive therapy with TCM treatment for reinforcing Shen and dissolving stasis in dominance has a definite clinical effect in treating MDS, it was not significantly associated with FAB typing, IPSS score, and chromosome abnormality of patients.


55. Tsiara SN, Kapsali HD, Panteli K, Christou L, Bourantas KL: Preliminary results of amifostine administration in combination with recombinant human erythropoietin in patients with myelodysplastic syndromes. J Exp Clin Cancer Res; 2001 Mar;20(1):35-8
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  • Amifostine is a cytoprotective agent mainly used in cancer therapies, in order to ameliorate the toxic effects of anticancer chemotherapy and radiotherapy.
  • Two patients had RAEB, four RA and one RARS.
  • The drug was administered in an outpatient basis in a dose of 300 mgr/m2, three times weekly for at least four weeks.
  • We administered at the same time erythropoietin 10.000 U subcutaneously.
  • Three patients, a woman with RA and two men, one with RA and another with RAEB improved the levels of Hb beyond 12,0 gr/dl and did not receive blood transfusions after the second week of treatment.
  • The drug was well tollerated without any side effects in all of the patients.
  • [MeSH-major] Amifostine / therapeutic use. Blood Transfusion. Cytoprotection. Erythropoietin / therapeutic use. Myelodysplastic Syndromes / therapy
  • [MeSH-minor] Aged. Anemia, Refractory / therapy. Anemia, Refractory, with Excess of Blasts / therapy. Bone Marrow Cells / pathology. Female. Humans. Male. Outpatients. Recombinant Proteins


56. 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.
  • Several small clinical studies give divergent informations about the potential of amifostine as single agent to improve hematopoiesis in MDS patients.
  • 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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57. 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.
  • PURPOSE: We report the first large prospective study of children with myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML) treated in a uniform fashion on Children's Cancer Group protocol 2891.
  • 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 were compared with patients with de novo AML.
  • 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.
  • CONCLUSION: Childhood subtypes of MDS and JMML represent distinct entities with distinct clinical outcomes.
  • 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
  • [MeSH-minor] Bone Marrow Transplantation. Child. Child, Preschool. Disease-Free Survival. Female. Follow-Up Studies. Humans. Male. Prognosis. Prospective Studies. Transplantation, Homologous


58. 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.
  • METHODS: The authors analyzed the outcome for 394 newly diagnosed patients treated between 1991 and 1999 with five regimens consisting of intermediate- or high-dose cytosine arabinoside (A) in combination with idarubicin (I), and introduced cyclophosphamide (C) and the new agents fludarabine (F) and topotecan (T) into new combinations with A.
  • 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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59. Tsimberidou AM, Colburn DE, Welch MA, Cortes JE, Verstovsek S, O'Brien SM, Albitar M, Kantarjian HM, Giles FJ: Anagrelide and imatinib mesylate combination therapy in patients with chronic myeloproliferative disorders. Cancer Chemother Pharmacol; 2003 Sep;52(3):229-34
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  • [Title] Anagrelide and imatinib mesylate combination therapy in patients with chronic myeloproliferative disorders.
  • PURPOSE: The tyrosine kinase inhibitor imatinib mesylate inhibits the function of the Bcr-Abl oncoprotein associated with Philadelphia-positive chronic myelogenous leukemia (CML).
  • The objectives of this study were to investigate the feasibility and safety of imatinib mesylate and anagrelide combination therapy in patients with Ph-positive CML or chronic myeloproliferative disorders (MPD) with persistent thrombocythemia.
  • RESULTS: Of 22 patients identified, 18 had Ph-positive CML (chronic phase, 16 patients; accelerated phase, 2 patients), 1 had agnogenic myeloid metaplasia (AMM), 2 had essential thrombocythemia (ET) and 1 had MPD transformed into refractory anemia with excess blasts (RAEB).
  • Imatinib mesylate and anagrelide combination therapy was feasible and tolerable.
  • No responses were noted in patients with AMM, ET or MPD transformed into RAEB.
  • [MeSH-major] Enzyme Inhibitors / therapeutic use. Fibrinolytic Agents / therapeutic use. Myeloproliferative Disorders / drug therapy. Piperazines / therapeutic use. Pyrimidines / therapeutic use. Quinazolines / therapeutic use
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Benzamides. Chronic Disease. Drug Therapy, Combination. Female. Humans. Imatinib Mesylate. Male. Medical Records Systems, Computerized. Middle Aged. Retrospective Studies. Survival Analysis

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  • (PMID = 12783207.001).
  • [ISSN] 0344-5704
  • [Journal-full-title] Cancer chemotherapy and pharmacology
  • [ISO-abbreviation] Cancer Chemother. Pharmacol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Benzamides; 0 / Enzyme Inhibitors; 0 / Fibrinolytic Agents; 0 / Piperazines; 0 / Pyrimidines; 0 / Quinazolines; 0 / anagrelide; 8A1O1M485B / Imatinib Mesylate
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60. 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.
  • Laboratory studies consisted of a complete blood cell count, measurement of serum epo and determination of anti-epo antibodies using ELISA.
  • 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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61. Fenaux P, Gattermann N, Seymour JF, Hellström-Lindberg E, Mufti GJ, Duehrsen U, Gore SD, Ramos F, Beyne-Rauzy O, List A, McKenzie D, Backstrom J, Beach CL: Prolonged survival with improved tolerability in higher-risk myelodysplastic syndromes: azacitidine compared with low dose ara-C. Br J Haematol; 2010 Apr;149(2):244-9
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  • In the phase III AZA-001 trial, low-dose cytarabine (LDara-C), the most widely used low-dose chemotherapy in patients with higher-risk myelodysplastic syndrome (MDS) who are ineligible for intensive treatment, was found to be associated with poorer survival compared with azacitidine.
  • This analysis further compared the efficacy and the toxicity of these two drug regimens.
  • Azacitidine prolonged overall survival versus LDara-C in patients with poor cytogenetic risk, presence of -7/del(7q), and French-American-British subtypes refractory anaemia with excess blasts (RAEB) and RAEB in transformation.
  • When analyzed per patient year of drug exposure, azacitidine treatment was associated with fewer grade 3-4 cytopenias and shorter hospitalisation time than LDara-C in these higher-risk MDS patients.
  • [MeSH-major] Antimetabolites, Antineoplastic / therapeutic use. Azacitidine / therapeutic use. Cytarabine / therapeutic use. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Drug Administration Schedule. Erythrocyte Transfusion. Female. Humans. Male. Middle Aged. Survival Analysis. Treatment Outcome

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  • [ErratumIn] Br J Haematol. 2010 Jun;149(6):919
  • (PMID = 20136825.001).
  • [ISSN] 1365-2141
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / K24 CA111717
  • [Publication-type] Clinical Trial, Phase III; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; 04079A1RDZ / Cytarabine; M801H13NRU / Azacitidine
  • [Other-IDs] NLM/ NIHMS490238; NLM/ PMC4000023
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62. 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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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [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.
  • Out of the 10 who relapsed, four are alive and disease-free following an allograft.
  • Out of the 6 children given an allograft in first remission, two died of disease and four are alive in first remission.
  • Both children given an autograft died of disease.
  • 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).
  • Monosomy 7 was the most common abnormality (33% of cases).
  • 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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63. Arlet JB, Varet B, Hermine O, Capron L, Pouchot J, Chiche L: [Weight loss and fever in a 72-year-old man]. Rev Med Interne; 2010 Jun;31(6):453-7
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Transliterated title] Une AREB bien tassée...

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  • (PMID = 20347510.001).
  • [ISSN] 1768-3122
  • [Journal-full-title] La Revue de medecine interne
  • [ISO-abbreviation] Rev Med Interne
  • [Language] FRE
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] France
  • [Chemical-registry-number] 0 / Anthelmintics; 0 / Anticestodal Agents; F4216019LN / Albendazole
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64. Germing U, Strupp C, Kuendgen A, Aivado M, Giagounidis A, Hildebrandt B, Aul C, Haas R, Gattermann N: Refractory anaemia with excess of blasts (RAEB): analysis of reclassification according to the WHO proposals. Br J Haematol; 2006 Jan;132(2):162-7
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Refractory anaemia with excess of blasts (RAEB): analysis of reclassification according to the WHO proposals.
  • The French-American-British (FAB) classification assigns patients with myelodysplastic syndromes to the category of refractory anaemia with excess blasts (RAEB) if they have a medullary blast count of 5-20%, and/or a peripheral blast count of 2-5%.
  • The new World Health Organization (WHO) classification subdivides RAEB into RAEB I with a medullary blast count < or =10% and a peripheral blast count < or =5% and RAEB II with >10% medullary and/or >5% peripheral blasts.
  • RAEB II is also diagnosed if Auer rods are present.
  • In 558 patients, we analysed these subtypes of RAEB in terms of haematological characteristics, karyotype anomalies and prognosis.
  • RAEB I was diagnosed in 256 and RAEB II in 302 patients.
  • In the RAEB II group, 22% of patients had >5% peripheral blasts or the presence of Auer rods.
  • The median survival was 16 months for RAEB I as compared with 9 months for RAEB II.
  • Patients with Auer rods, regardless of their medullary and peripheral blast count, had no worse prognosis.
  • No significant differences were identified between the RAEB subtypes with respect to clinical, morphological, haematological and cytogenetic parameters.
  • The survival data support the WHO reclassification of RAEB based on peripheral and medullary blast counts and Auer rods.
  • The WHO classification is useful for diagnosis and provides risk stratification, supported by cytogenetic data for clinical decision making, identifying those RAEB patients with an unfavourable prognosis who should be offered chemotherapy or stem cell transplantation.
  • [MeSH-major] Anemia, Refractory, with Excess of Blasts / classification

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  • [ErratumIn] Br J Haematol. 2006 Jul;134(2):247
  • (PMID = 16398650.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
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65. 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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  • [Title] A case of monocytic leukaemia cutis in a patient with myelodysplastic syndrome transforming to acute myeloid leukaemia.
  • A 49-year-old woman presented with a 1-year-history of a widespread eruption which proved to be due to leukaemia cutis.
  • Subsequently, she developed pancytopaenia and a bone marrow biopsy revealed refractory anaemia with excess blasts in transformation (RAEB-T) with a high monoblastic component.
  • This transformed into acute myeloid leukaemia.
  • Leukaemia cutis in this context is well described but in this patient it became manifest 1 year prior to referral to the dermatologist.
  • 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


66. Lü X, Qiu HX, Qiu HR, Zhang SJ, Xu J, Xu W, Wu HX, Li JY, Shao JZ: [A case of myelodysplastic syndrome with aberrant evolution of chromosome 1 and 11 in 6 years of follow-up]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2010 Apr;18(2):469-72
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  • This study was aimed to investigate the relationship between cytogenetic evolution and disease progression in patient with MDS-RAEB.
  • By a long term (6 years) follow-up of a patient with MDS-RAEB, peripheral blood cell count, bone marrow cell morphology and conventional cytogenetics were monitored regularly.
  • The results indicated that this patient was failed with conventional chemotherapy of AML, but had response to ATRA and 6-MP in the 72 months follow-up.
  • At initial diagnosis, the cytogenetics analysis showed normal karyotype, whereas 46, XY, 2q+[1]/46, XY[19] was found at 48 months, 46, XY, dup(1q)[3]/46, XY[7] at 56 months, and dup (1) as well as der (11) with complex karyotype at 68 months, which was accompanied by progressive decrease of platelet count.


67. Grossi A, Fabbri A, Santini V, Leoni F, Nozzoli C, Longo G, Pagliai G, Ciolli S, Rossi Ferrini P: Amifostine in the treatment of low-risk myelodysplastic syndromes. Haematologica; 2000 Apr;85(4):367-71
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  • [Title] Amifostine in the treatment of low-risk myelodysplastic syndromes.
  • BACKGROUND AND OBJECTIVE: The phosphorylated aminothiol agent amifostine (Ethyol) protects bone marrow and other tissues from toxicity due to ionizing radiation and antineoplastic drugs, and stimulates progenitors from normal and myelodysplastic bone marrow.
  • DESIGN AND METHODS: In a pilot phase II study we treated 26 patients with low risk MDS (13 RA, 2 RARS, 2 CMML, 9 RAEB with blasts < 10%) with amifostine (200 mg/m(2 )x 3/week for 4 weeks).
  • Unexpectedly a significant decrease in soluble transferrin receptor level at week 4 of therapy, compared to the basal level (p<0.04), was observed in the whole population of patients.
  • Neutropenia is more likely to be corrected than anemia or thrombocytopenia.
  • [MeSH-major] Amifostine / administration & dosage. Myelodysplastic Syndromes / drug therapy. Radiation-Protective Agents / administration & dosage
  • [MeSH-minor] Aged. Aged, 80 and over. Blood Cell Count / drug effects. Erythropoietin / blood. Female. Humans. Male. Middle Aged. Pancytopenia / drug therapy. Pilot Projects. Receptors, Transferrin / blood. Thrombopoietin / blood

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  • (PMID = 10756361.001).
  • [ISSN] 0390-6078
  • [Journal-full-title] Haematologica
  • [ISO-abbreviation] Haematologica
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] ITALY
  • [Chemical-registry-number] 0 / Radiation-Protective Agents; 0 / Receptors, Transferrin; 11096-26-7 / Erythropoietin; 9014-42-0 / Thrombopoietin; M487QF2F4V / Amifostine
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68. Chen SC, Jiang B, Da WM, Gong M, Guan M: [Curative effects of cyclosporin A therapy upon myelodysplastic syndrome]. Zhonghua Yi Xue Za Zhi; 2006 Oct 17;86(38):2711-5
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  • [Title] [Curative effects of cyclosporin A therapy upon myelodysplastic syndrome].
  • OBJECTIVE: To evaluate the efficacy of cyclosporin A (CsA) in treatment of myelodysplastic syndromes (MDS).
  • METHODS: Thirty-three patients with MDS, including refractory anemia (RA, n = 24), refractory anemia with ringed sideroblasts (RAS, n = 2), and refractory anemia with excess blasts (RAEB, n = 7), 23 males and 10 females, aged 46 (6 approximately 71), hospitalized in 4 CsA, grade 3 hospitals in Beijing who failed to respond to folic acid and vitamin B12, received CsA 3 approximately 5 mg x kg(-1)x d(-1), 2 times per days, taken orally in 2 separate doses for at least 3 months (2 approximately 27 months).
  • During the course of treatment the dosage was adjusted according to the CsA blood concentration and curative effect.
  • RESULTS: After 3 months of the treatment, the hematological improvement (HI) was observed in 18 of the 32 evaluative patients (56.3%) by the criteria of the International Working Group (IWG).
  • At the end of the follow-up 4 patients showed alteration of disease progression, including 1 case of complete remission (CR) and 3 cases of partial remission (PR), and 16 patients showed homological improvement, responders numbering 20 totally, with a response rate of 62.5% (20/32).
  • CONCLUSION: Improving the clinical manifestations and lengthening the survival time, CsA therapy is effective in the patients with RA or RAEB, and both hypoplastic bone marrow and hyperplastic bone marrows respond to the therapy.
  • CsA therapy is potentially the most effective therapy for MDS.
  • [MeSH-major] Cyclosporine / therapeutic use. Immunosuppressive Agents / therapeutic use. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Child. Drug Administration Schedule. Female. Follow-Up Studies. Humans. Male. Middle Aged. Prospective Studies. Treatment Outcome


69. Hamaki T, Kami M, Kim SW, Onishi Y, Kishi Y, Murashige N, Hori A, Kojima R, Sakiyama M, Imataki O, Heike Y, Tanosaki R, Masuo S, Miyakoshi S, Taniguchi S, Tobinai K, Takaue Y: Reduced-intensity stem cell transplantation from an HLA-identical sibling donor in patients with myeloid malignancies. Bone Marrow Transplant; 2004 May;33(9):891-900
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • The purpose of this study was to evaluate the feasibility and efficacy of allogeneic hematopoietic stem cell transplantation with a reduced-intensity regimen (RIST) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).
  • The diagnoses included AML (n=14), leukemia evolving from MDS (n=10), and MDS (refractory anemia with excess blasts n=6, refractory anemia n=6).
  • A total of 17 patients developed grade II-IV acute GVHD, and 27 developed chronic GVHD.
  • A total of 12 patients died (four disease progression, six transplantation-related complications, and two others).
  • Estimated 1-year disease-free survival (DFS) in low- and high-risk groups was 85 and 64%, respectively.
  • We conclude that RIST can be performed safely in elderly patients with myeloid malignancies, and has therapeutic potential for those who fail conventional chemotherapy.
  • In view of the significant association between GVHD or ATG and DFS, defined management of GVHD following RIST should become a major target of clinical research.
  • [MeSH-major] HLA Antigens / chemistry. Hematopoietic Stem Cell Transplantation / methods. Leukemia, Myeloid, Acute / therapy. Myelodysplastic Syndromes / therapy. Transplantation, Homologous / methods. Vidarabine / analogs & derivatives
  • [MeSH-minor] Adult. Aged. Antigens, CD3 / chemistry. Antilymphocyte Serum / pharmacology. Antineoplastic Agents / pharmacology. Antineoplastic Agents, Alkylating / pharmacology. Busulfan / pharmacology. Cladribine / pharmacology. Disease-Free Survival. Feasibility Studies. Female. Graft vs Host Disease / prevention & control. Graft vs Leukemia Effect. Granulocyte Colony-Stimulating Factor / metabolism. Histocompatibility Testing. Humans. Male. Middle Aged. Recurrence. Time Factors. Transplantation Chimera. Treatment Outcome

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  • (PMID = 15048142.001).
  • [ISSN] 0268-3369
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antigens, CD3; 0 / Antilymphocyte Serum; 0 / Antineoplastic Agents; 0 / Antineoplastic Agents, Alkylating; 0 / HLA Antigens; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 47M74X9YT5 / Cladribine; FA2DM6879K / Vidarabine; G1LN9045DK / Busulfan; P2K93U8740 / fludarabine
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70. Qin YZ, Liu YR, Li JL, Fu JY, Chang Y, Lu DP, Guo NL, Chen SS: [Follow up Detection of AML/ETO Fushion Transcripts after Chemotherapy or Bone Marrow Transplantation in Leukemia Patients]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2001 Jun;9(2):139-142
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  • [Title] [Follow up Detection of AML/ETO Fushion Transcripts after Chemotherapy or Bone Marrow Transplantation in Leukemia Patients]
  • Expression of AML1/ETO mRNA was observed in bone marrow cells from 49 untreated leukemic patients, and continuously detected during different periods after chemotherapy (12 cases) or bone marrow transplantation (8 cases).
  • The results showed that AML1/ETO mRNA could be expressed in cells from AML-M(2), AML-M(4) and MDS-RAEB-T patients.
  • The positive expression changed into negative at different duration in patients who achieved complete remission either by chemotherapy (9 cases), allogeneic bone marrow transplantation (5 cases) and autologous peripheral blood stem cell transplantation (1 case), and they were sustained in complete remission status.
  • These observations suggest that AML1/ETO chimeric mRNA could disappeared after chemotherapy or bone marrow transplantation.
  • Regular detection is necessary for leukemic patients.

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  • (PMID = 12578621.001).
  • [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] JOURNAL ARTICLE
  • [Publication-country] China
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71. Lu Y, Wu T, Cao XY, Wang JB, Yin YM, Lu DP: [Effects of allogeneic hematopoietic stem cell transplantation on 60 patients with myelodysplastic syndrome]. Zhonghua Nei Ke Za Zhi; 2010 Mar;49(3):200-3
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • OBJECTIVE: To evaluate the clinical outcome of all-ogeneic hematopoietic stem cell transplantation (all-HSCT) for myelodysplastic syndrome (MDS).
  • Cyclosporine A and short-course MTX were used for graft-versus-host disease (GVHD) prophylaxis.
  • DFS rates in RA/RAS/5q-, RCMD, RAEB-I/RAEB-II and acute myelocytic leukemia (AML) subgroups were 84.6%, 80.0%, 81.0%, 56.2%, respectively (P > 0.05).
  • DFS rates for percentages of blasts in bone marrow pre-transplant were 87.0%, 65.5%, 75.0% in < 5% blasts, 5% - 20% blasts, > 20% blasts subgroups, respectively (P > 0.05).
  • CONCLUSIONS: Since favorable clinical outcomes have been seen in all kinds of MDS by allo-HSCT, HSCT should be the first-line therapy for MDS.
  • No significant differences are found based on different stem cell donors and the percentages of bone marrow blasts pre-HSCT, unrelated or haploidentical donors should be important alternatives if there is no identical sibling available.
  • Chemotherapy before transplantation is not necessary except overt acute leukemia.
  • A larger clinical study is needed to evaluate the clinical outcomes of allo-HSCT in MDS.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation. Myelodysplastic Syndromes / therapy
  • [MeSH-minor] Adolescent. Adult. Disease-Free Survival. Female. Humans. Male. Middle Aged. Treatment Outcome. Young Adult


72. 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.
  • A diagnosis of trilineage extramedullary myeloid tumor was reached.
  • 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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73. 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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74. 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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  • This is a report of the clinical, morphologic and cytogenetic features of 52 cases of primary MDS occurring in adults under the age of 50 years.
  • Cases secondary to chemotherapy or radiotherapy were excluded.
  • The interval between onset of symptoms and diagnosis was brief (median, 4 weeks; range, 1-32 weeks).
  • 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.
  • Abnormalities involving chromosome 7 was the most frequent cytogenetic abnormality (31%).
  • 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.


75. Choi EH, Ok HE, Yoon Y, Magnuson BA, Kim MK, Chun HS: Protective effect of anthocyanin-rich extract from bilberry (Vaccinium myrtillus L.) against myelotoxicity induced by 5-fluorouracil. Biofactors; 2007;29(1):55-65
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  • The toxicities associated with 5-fluorouracil (5-FU), a potent broad-spectrum chemotherapeutic agent, can not only affect the morbidity and the efficacy of chemotherapy but also limit its clinical use.
  • The objective of this study is to investigate the effects of a commercial anthocyanin-rich extract from bilberry (AREB) against 5-FU-induced myelotoxicity in vivo, and against chemosensitivity to 5-FU in vitro.
  • Oral administration of 500 mg/kg of AREB for 10 days significantly increased the number of red blood cells, neutrophils, and monocytes in peripheral blood to 1.2-fold, 9-fold, and 6-fold, respectively, compared with those seen after treatment with 5-FU alone (p< 0.05-0.001).
  • The hypocellularity of the spleen and bone marrow caused by 5-FU was also distinctly alleviated in the AREB-treated group.
  • Furthermore, AREB treatment with 50 and 100 microg/ml as a monomeric anthocyanin did not interfere with, but rather enhanced the chemotherapeutic efficacy of 5-FU in vitro.
  • These results suggest that AREB may have protective potential against 5-FU-induced myelotoxiciy and/or the ability to enhance the chemotherapeutic effectiveness of 5-FU.
  • [MeSH-minor] Administration, Oral. Animals. Bone Marrow Cells / cytology. Bone Marrow Cells / drug effects. Cell Count. Cell Survival / drug effects. Chromatography, High Pressure Liquid. Dose-Response Relationship, Drug. Erythrocytes / cytology. Erythrocytes / drug effects. HT29 Cells. Humans. Male. Mice. Mice, Inbred C57BL. Monocytes / cytology. Monocytes / drug effects. Neutrophils / cytology. Neutrophils / drug effects. Plant Extracts / administration & dosage. Plant Extracts / pharmacology. Spleen / cytology. Spleen / drug effects. Time Factors

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  • (PMID = 17611294.001).
  • [ISSN] 0951-6433
  • [Journal-full-title] BioFactors (Oxford, England)
  • [ISO-abbreviation] Biofactors
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Anthocyanins; 0 / Plant Extracts; 84082-34-8 / Vaccinium myrtillus extract; U3P01618RT / Fluorouracil
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76. Xu ZF, Qin TJ, Zhang Y, Liu KQ, Hao YS, Xiao ZJ: [Cyclosporine A in combination with thalidomide for the treatment of patients with myelodysplastic syndromes]. Zhonghua Xue Ye Xue Za Zhi; 2010 Jul;31(7):451-5
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  • [Title] [Cyclosporine A in combination with thalidomide for the treatment of patients with myelodysplastic syndromes].
  • METHODS: A total of thirty-seven patients with MDS-RCMD or-RAEB-I were treated with CsA in combination with thalidomide.
  • Some patients developed grades I-II hepatic or nephritic impairment, constipation, lethargy, dizziness, edema, rashes or numbness, and all were tolerable and reversible.
  • CONCLUSION: CsA in combination with thalidomide appears to be effective mainly in inducing HI-E and relatively well-tolerated for the treatment of patients with MDS.
  • [MeSH-minor] Anemia, Refractory, with Excess of Blasts / drug therapy. Humans. Myelodysplastic Syndromes / drug therapy. Treatment Outcome

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  • (PMID = 21122398.001).
  • [ISSN] 0253-2727
  • [Journal-full-title] Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi
  • [ISO-abbreviation] Zhonghua Xue Ye Xue Za Zhi
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 4Z8R6ORS6L / Thalidomide; 83HN0GTJ6D / Cyclosporine
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77. 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.
  • Myelodysplastic syndrome (MDS) often transforms into acute leukemia, usually of a myeloid phenotype.
  • 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.
  • Southern-blot analysis revealed rearrangement of the immunoglobulin heavy chain, but no additional chromosomal abnormality characteristic of ALL-L3 was detected.
  • 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


78. Shi J, Shao Z, Liu H, Li K, Song L, Zhang Y, Zheng Y, Chen G, Chu Y, He H, Zhao M, He G, Feng B, Hao Y, Yang T, Yang C: [Study on the transformation from myelodysplastic syndromes into acute leukemias]. Zhonghua Xue Ye Xue Za Zhi; 2001 Jul;22(7):351-4
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  • [Title] [Study on the transformation from myelodysplastic syndromes into acute leukemias].
  • OBJECTIVE: To study the patterns of transformation from myelodysplastic syndromes (MDS) into acute leukemias (AL).
  • METHODS: Leukemic transformation of MDS patients was dynamically followed up and the clinical manifestations, peripheral blood and bone marrow pictures, karyotypes, immunophenotypes, response to treatment and prognosis of post MDS acute leukemia (postMDS-AL) were observed.
  • RESULTS: During the past eight year and seven months, 21 (13.91%) of 151 MDS patients progressed to overt leukemia with a median interval of 5 (1 - 21) months.
  • There were no significant differences among the rates of leukemia from RA, RAEB and RAEB-t groups.
  • The transformation was developed either gradually or rapidly.
  • There were five parameters related to the leukemic transformation: under 40 years of age, pancytopenia, more than 0.15 blasts in bone marrow, at least two types of abnormal karyotype and combined chemotherapy.
  • All of the 21 post MDS-AL were acute myeloid leukemia (AML); and most of them were M(2), M(4) and M(5).
  • Two (9.52%) post MDS-AML developed extramedullary infiltration.
  • After evolving into AML, 8 (47.06%) patients developed abnormal karyotypes.
  • A low complete remission rate (31.25%) and short survival duration with median survival of 6 (1 - 28) months were found in patients with post MDS-AML treated by induction therapy.
  • [MeSH-major] Leukemia / pathology. Myelodysplastic Syndromes / pathology
  • [MeSH-minor] Acute Disease. Adolescent. Adult. Aged. Cell Transformation, Neoplastic. Cocarcinogenesis. Disease Progression. Female. Follow-Up Studies. Humans. Immunophenotyping. Karyotyping. Male. Middle Aged. Prognosis. Young Adult


79. Raza A, Qawi H, Lisak L, Andric T, Dar S, Andrews C, Venugopal P, Gezer S, Gregory S, Loew J, Robin E, Rifkin S, Hsu WT, Huang RW: Patients with myelodysplastic syndromes benefit from palliative therapy with amifostine, pentoxifylline, and ciprofloxacin with or without dexamethasone. Blood; 2000 Mar 1;95(5):1580-7
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  • [Title] Patients with myelodysplastic syndromes benefit from palliative therapy with amifostine, pentoxifylline, and ciprofloxacin with or without dexamethasone.
  • Thirty-five patients with myelodysplastic syndrome (MDS) were registered on protocol MDS 96-02 and were receiving continuous therapy with pentoxifylline 800 mg 3 times a day and ciprofloxacin 500 mg twice a day by mouth; dexamethasone was added to the regimen for the partial responders and the nonresponders after 12 weeks at a dose of 4 mg by mouth every morning for 4 weeks.
  • Amifostine was administered intravenously 3 times a week at 3 dose levels (200 mg/M(2), 300 mg/M(2), and 400 mg/M(2)) to cohorts of 10 patients each.
  • Therapy has been continued for 1 year in responders.
  • Twenty-nine have completed at least 12 weeks of therapy and are available for response evaluation.
  • Of the 21 men and 8 women (median age, 67 years), 20 had refractory anemia (RA), 3 had RA with ringed sideroblasts (RARS), 5 had RA with excess blasts (RAEB), and 1 had chronic myelomonocytic leukemia (CMMoL).
  • Interestingly, the responses were frequently slow to appear, and continued improvement in counts was seen up to 12 months of therapy and beyond.
  • This study supports the feasibility of treating patients with MDS with the unique approach of cytoprotection and anticytokine therapies as well as the principle that prolonged commitment to treatment is desirable when noncytotoxic agents are administered. (Blood.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Myelodysplastic Syndromes / drug therapy. Palliative Care
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Amifostine / administration & dosage. Amifostine / adverse effects. Anorexia / chemically induced. Blood Cell Count / drug effects. Ciprofloxacin / administration & dosage. Ciprofloxacin / adverse effects. Dexamethasone / administration & dosage. Dexamethasone / adverse effects. Female. Gastrointestinal Diseases / chemically induced. Hematologic Diseases / chemically induced. Humans. Hypotension / chemically induced. Male. Middle Aged. Pentoxifylline / administration & dosage. Pentoxifylline / adverse effects. Treatment Outcome


80. 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.


81. Carpiuc I, Antoun S, Delabarthe A, Driss B, Vantelon JM, Griscelli F, Fenaux R, Ribrag V: Segmental coecal cytomegalovirus colitis during fludarabine, cytarabine and mitoxantrone induction chemotherapy for myelodysplastic syndrome. Leuk Lymphoma; 2002 Aug;43(8):1701-3
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  • [Title] Segmental coecal cytomegalovirus colitis during fludarabine, cytarabine and mitoxantrone induction chemotherapy for myelodysplastic syndrome.
  • We report the case of a 59-year-old woman treated for a refractory anemia with excess blasts (RAEB) who developed cytomegalovirus (CMV) colitis during induction therapy combining fludarabine, cytarabine and mitoxantrone.
  • CMV infection occurred rarely during cytarabine and anthracyclin based induction therapy for acute myelogenous leukemia or RAEB.
  • [MeSH-major] Anemia, Refractory, with Excess of Blasts / drug therapy. Antineoplastic Combined Chemotherapy Protocols / adverse effects. Cecal Diseases / etiology. Colitis / etiology. Cytarabine / adverse effects. Cytomegalovirus Infections / etiology. Vidarabine / adverse effects. Vidarabine / analogs & derivatives

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  • (PMID = 12400617.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; BZ114NVM5P / Mitoxantrone; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine
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82. 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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  • [Title] Gemtuzumab, fludarabine, cytarabine, and cyclosporine in patients with newly diagnosed acute myelogenous leukemia or high-risk myelodysplastic syndromes.
  • BACKGROUND: Gemtuzumab is used to treat patients with previously untreated or recurrent acute myelogenous leukemia (AML).
  • Resistance to gemtuzumab is associated with blast multidrug resistance (MDR).
  • 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


83. Wallvik J, Stenke L, Bernell P, Nordahl G, Hippe E, Hast R: Serum erythropoietin (EPO) levels correlate with survival and independently predict response to EPO treatment in patients with myelodysplastic syndromes. Eur J Haematol; 2002 Mar;68(3):180-5
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  • [Title] Serum erythropoietin (EPO) levels correlate with survival and independently predict response to EPO treatment in patients with myelodysplastic syndromes.
  • Treatment with recombinant erythropoietin (EPO) can alleviate anaemia in patients with myelodysplastic syndromes (MDS).
  • The present study, based on a long-term follow-up of 68 MDS patients (26RA, 16 RAS, 26 RAEB) treated with EPO alone, pinpoints pre-treatment variables associated with response induction, response duration and overall survival.
  • Using univariate logistic regression models, responders displayed significantly lower baseline serum EPO levels (S-EPO), more often normal bone marrow blast cell content (RA/RAS vs. RAEB), normal cytogenetics and no need for erythrocyte transfusion.
  • In a multiple logistic regression model, S-EPO (P=0.009), marrow blast content (P=0.031) and erythrocyte transfusion need (P=0.024) remained associated with response induction.
  • The probability of response for a patient with S-EPO >50UL1, RA/RAS and no transfusion need was 0.79 (0.53-0.93, 95% CI).
  • The median overall survival time from start of EPO treatment was 26 months, significantly longer for responders than for non-responders (49 vs. 18 months, P=0.018).
  • Survival was also predicted by baseline S-EPO; patients with S-EPO >50UL1 (n=50) had a median survival of 17 months, as compared to 65 months for those with S-EPO >50UL1 (n=14, P=0.024).
  • The international prognostic scoring system (IPSS) for MDS predicted survival (P=0.003) and progression to acute leukemia (P<0.001) but not response to EPO treatment.
  • Furthermore, in a logistic regression model with S-EPO and IPSS, S-EPO (but not IPSS) was again a significant predictor for response (P=0.007).
  • Our data facilitate the optimal selection of MDS patients suitable for EPO treatment and pinpoint S-EPO as a powerful predictor of response and overall survival in MDS.
  • [MeSH-major] Erythropoietin / blood. Erythropoietin / therapeutic use. Myelodysplastic Syndromes / blood. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Anemia, Refractory / blood. Anemia, Refractory / drug therapy. Anemia, Refractory, with Excess of Blasts / blood. Anemia, Refractory, with Excess of Blasts / drug therapy. Bone Marrow Cells / pathology. Erythrocyte Transfusion. Female. Hemoglobins / analysis. Humans. Logistic Models. Male. Middle Aged. Prognosis. Recombinant Proteins. Survival Rate


84. Jakob A, Hirsch FW, Engelhardt M: Successful treatment of a patient with myelodysplastic syndrome (RAEB) with Darbepoetin-alfa in combination with Pegfilgrastim. Ann Hematol; 2005 Oct;84(10):694-5
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  • [Title] Successful treatment of a patient with myelodysplastic syndrome (RAEB) with Darbepoetin-alfa in combination with Pegfilgrastim.
  • [MeSH-major] Anemia, Refractory, with Excess of Blasts / drug therapy. Erythropoietin / analogs & derivatives. Granulocyte Colony-Stimulating Factor / administration & dosage
  • [MeSH-minor] Aged. Darbepoetin alfa. Drug Therapy, Combination. Filgrastim. Humans. Leukocyte Count / methods. Male. Recombinant Proteins

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  • (PMID = 15931534.001).
  • [ISSN] 0939-5555
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Letter
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Recombinant Proteins; 11096-26-7 / Erythropoietin; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 15UQ94PT4P / Darbepoetin alfa; 3A58010674 / pegfilgrastim; PVI5M0M1GW / Filgrastim
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85. Feldman EJ, Cortes J, DeAngelo DJ, Holyoake T, Simonsson B, O'Brien SG, Reiffers J, Turner AR, Roboz GJ, Lipton JH, Maloisel F, Colombat P, Martinelli G, Nielsen JL, Petersdorf S, Guilhot F, Barker J, Kirschmeier P, Frank E, Statkevich P, Zhu Y, Loechner S, List A: On the use of lonafarnib in myelodysplastic syndrome and chronic myelomonocytic leukemia. Leukemia; 2008 Sep;22(9):1707-11
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  • [Title] On the use of lonafarnib in myelodysplastic syndrome and chronic myelomonocytic leukemia.
  • In a multicenter study, 67 patients with advanced myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) were treated with a continuous oral dose of 200-300 mg of lonafarnib and were evaluated for hematologic, pathologic and pharmacodynamic response.
  • There were 32 patients with MDS (RAEB-20 and RAEB-t-12) and 35 with CMML.
  • Of the 19 patients who were platelet transfusion-dependent prior to treatment, 5 (26%) became transfusion-free for a median duration of 185 days.
  • A decrease in the farnesylation of the HDJ-2 protein measured in patient-derived cells was observed in the majority of patients during treatment with lonafarnib, but no clear correlation between changes in farnesylation and clinical effect could be made.
  • Gastrointestinal toxicity was significant with 19% of patients discontinuing therapy due to diarrhea, nausea and/or anorexia.
  • [MeSH-major] Leukemia, Myelomonocytic, Chronic / drug therapy. Myelodysplastic Syndromes / drug therapy. Piperidines / administration & dosage. Pyridines / administration & dosage
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Drug Monitoring. Enzyme Inhibitors / therapeutic use. Farnesyltranstransferase / antagonists & inhibitors. Farnesyltranstransferase / metabolism. Gastrointestinal Diseases / chemically induced. Humans. Maximum Tolerated Dose. Middle Aged. Remission Induction. Treatment Outcome


86. Dixit A, Chatterjee T, Mishra P, Choudhary DR, Mahapatra M, Saxena R, Choudhry VP: Cyclosporin A in myelodysplastic syndrome: a preliminary report. Ann Hematol; 2005 Sep;84(9):565-8
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  • Therapeutic approaches are not well established in patients with myelodysplastic syndrome (MDS).
  • We evaluated response to cyclosporin A (CyA) in 19 cases with MDS who were enrolled for the study [13 refractory anemia (RA), 5 refractory anemia with excess of blasts (RAEB), and 1 refractory anemia with ringed sideroblasts (RARS)].
  • Fifteen patients were transfusion dependent and the rest were not transfusion dependent but with a hemoglobin range of 6.4-8.8 g% with a mean of 7.4 g%.
  • Four cases of RA showed minor response and two cases of RA did not respond to CyA therapy.
  • A minor response was also seen in one RAEB and one RARS case, while one RAEB case that initially showed a major response relapsed on therapy.
  • The first effect of therapy was evident after a mean period of 2.5 months.
  • One case developed renal failure on therapy and later died of septicemia.
  • CyA could be an effective mode of therapy in patients with MDS especially those having RA.
  • [MeSH-major] Cyclosporine / administration & dosage. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Adult. Aged. Anemia, Refractory / drug therapy. Anemia, Refractory, with Excess of Blasts / drug therapy. Anemia, Sideroblastic / drug therapy. Bone Marrow / pathology. Female. Humans. Leukocyte Count. Male. Middle Aged. Platelet Count. Renal Insufficiency / chemically induced. Treatment Outcome


87. 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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88. 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.
  • This is consistent with the finding that TPO-induced in vitro megakaryocytopoiesis is not uniformly observed in MDS.
  • 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.
  • These findings may be of use when designing a clinical trial of TPO for MDS.
  • [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


89. Yang SS, Chau T, Dai MS, Lin SH: Steroid-induced tumor lysis syndrome in a patient with preleukemia. Clin Nephrol; 2003 Mar;59(3):201-5
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  • Tumor lysis syndrome (TLS) is a well recognized complication of chemotherapy and radiotherapy for leukemia, lymphoma as well as rapidly growing malignancies.
  • Less described is the occurrence of TLS following steroid therapy alone.
  • Herein, we report on a 32-year-old male with myelodysplastic syndrome, characterized by refractory anemia with excess blasts in transformation, who developed acute oliguric renal failure 12 hours after methylprednisolone 1.0 g for presumed autoimmune thrombocytopenia.
  • Prophylactic management prior to the use of steroid therapy for a variety of purposes is absolutely required in high-risk patients.

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  • (PMID = 12653264.001).
  • [ISSN] 0301-0430
  • [Journal-full-title] Clinical nephrology
  • [ISO-abbreviation] Clin. Nephrol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Glucocorticoids; X4W7ZR7023 / Methylprednisolone
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90. Kokhno AV, Parovichnikova EN, Mikhaĭlova EA, Ustinova EN, Kaplanskaia IB, Dvirnyk VN, Ol'shanskaia IuV, Domracheva EV, Savchenko VG: [Efficiency of cyclosporin A therapy in patients with myelodysplastic syndrome]. Ter Arkh; 2010;82(8):48-53
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  • [Title] [Efficiency of cyclosporin A therapy in patients with myelodysplastic syndrome].
  • AIM: To evaluate the efficacy of cyclosporin A (CsA) in patients with myelodysplastic syndromes (MDS) and to identify determinants of a response to this therapy.
  • Thirty-two patients were given CsA as first-line therapy; 20 patients took the agent after prior therapy.
  • RESULTS: The efficacy of CsA used as first- and second-line therapy was 56 and 55%, respectively; complete remissions were achieved in 19 and 20% of cases.
  • Baseline refractory anemia (RA) transformed to RA with excess blasts (RAEB) in 31% of cases; baseline RAEB did to acute myeloid leukemia in 34%.
  • Overall survival was significantly associated with bone marrow (BM) blast cell percentage (< 5% or > 5%; p = 0.0009), BM cellularity (hypoplasia and focal hypoplasia of hematopoiesis or BM hyperplasia; p = 0.03), focal polyclonal lymphoid infiltration in the BM (p = 0.01) and karyotype anomalies (low, moderate, and high risks; p = 0.001).
  • CONCLUSION: CsA is the drug of choice in treating patients with MDS, including RA, RA with ringed sideroblasts, refractory cytopenia with multilineage dysplasia, with hypoplasia of hematopoiesis, with nodular polyclonal lymphoid infiltration in the BM, a normal karyotype or changes corresponding to a low or moderate IPSS risk.
  • [MeSH-major] Cyclosporine / therapeutic use. Immunosuppressive Agents / therapeutic use. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Bone Marrow / pathology. Chromosome Aberrations. Dose-Response Relationship, Drug. Female. Humans. Kaplan-Meier Estimate. Karyotyping. Male. Middle Aged. Prognosis. Young Adult


91. 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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  • [Title] Phase II study of topotecan and thalidomide in patients with high-risk myelodysplastic syndromes.
  • 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.
  • Patients received three 21-day cycles of topotecan 1.25 mg/m(2) on days 1-5, which was repeated for two additional cycles in patients whose bone marrow blast percentages did not decrease.
  • Patients were monitored throughout the trial for hematologic and clinical adverse events, and efficacy was assessed using International Working Group (IWG) criteria.
  • 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.
  • Thirty-eight patients were evaluable for response: nine (24%) had hematologic improvement and 13 (34%) had stable disease.
  • Responses occurred in patients with all disease subtypes.
  • 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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92. Kaeferstein A, Krug U, Tiesmeier J, Aivado M, Faulhaber M, Stadler M, Krauter J, Germing U, Hofmann WK, Koeffler HP, Ganser A, Verbeek W: The emergence of a C/EBPalpha mutation in the clonal evolution of MDS towards secondary AML. Leukemia; 2003 Feb;17(2):343-9
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  • [Title] The emergence of a C/EBPalpha mutation in the clonal evolution of MDS towards secondary AML.
  • Recently, mutations in the transcription factor CCAAT/ enhancer binding protein alpha (C/EBPalpha) have been described in acute myeloid leukemia (AML).
  • No mutations were found in patients with refractory anemia (0/27), refractory anemia with ringed sideroblasts (0/7), refractory anemia with excess of blasts (RAEB 0/16) or chronic myelomonocytic leukemia (CMML 0/5).
  • One out of 13 patients with RAEB-T/AML secondary to MDS showed a mutation in the C/EBPalpha gene.
  • However, the dominant protein translated was the C/EBPalpha isoform p30, which was previously shown to inhibit the DNA-binding and transactivation properties of C/EBPalpha p42.
  • Interestingly this mutation could not be detected at diagnosis in the initial RAEB and RAEB-T stage.
  • The mutation appeared at relapse after chemotherapy for RAEB-T.
  • We conclude that the C/EBPalpha mutation was not essential for the initial blast accumulation.
  • The emergence of a bast clone carrying a C/EBPalpha mutation at relapse indicates that this mutation may confer a growth advantage in a myeloid cell with an established differentiation block.
  • [MeSH-major] Bone Marrow Cells / pathology. CCAAT-Enhancer-Binding Protein-alpha / metabolism. Leukemia, Myeloid, Acute / genetics. Mutation. Myelodysplastic Syndromes / genetics
  • [MeSH-minor] Adult. Aged. Anemia, Refractory, with Excess of Blasts / genetics. Anemia, Refractory, with Excess of Blasts / pathology. Base Sequence. DNA Primers. Disease Progression. Female. Humans. Male. Middle Aged. Polymerase Chain Reaction. Polymorphism, Single-Stranded Conformational


93. Novitzky N: Myelodysplastic syndromes in children. A critical review of the clinical manifestations and management. Am J Hematol; 2000 Apr;63(4):212-22
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  • [Title] Myelodysplastic syndromes in children. A critical review of the clinical manifestations and management.
  • Consequently, to outline the natural history of the disease better we have retrospectively analysed case reports and series published in English between 1982 and 1996.
  • This study also included children with juvenile chronic myelomonocytic leukaemia (JCML) and monosomy 7 (Mo7).
  • Constitutional alterations were described in 68 (20%) where refractory anemia (RA) and RA with excess of blasts (RAEB) predominated and were associated with a significantly longer survival.
  • Amid those with Mo7, the clinical and laboratory characteristics as well as survival, closely followed their FAB type.
  • Of the treatment options described, survival was significantly higher in those who underwent bone marrow transplant (BMT) (46.9%; P = 0.00021).
  • Among children with JMML (CMML/JCML) not receiving a BMT, time to death was shortest in those best described as JCML (absence of constitutional and karyotypic derangement, thrombocytopenia and elevated Hb F).
  • Finally, BMT remains the treatment of choice for those with primary MDS, as intensive chemotherapy is no better than supportive measures.


94. 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.
  • Patients with acute myelogenous leukemia (AML) were excluded.
  • Graft-versus-host-disease (GVHD) prophylaxis was cyclosporine (CsA)/steroids (19 patients) or CsA/mycophenolate mofetil (MMF; 4 patients).
  • Grafts were HLA matched at Class I (A and B) at low resolution and Class II (DRB1) at the allelic level, resulting in 16 (70%) 4/6 and 7 (30%) 5/6 matched transplants.
  • 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%).
  • Four patients relapsed with a cumulative incidence of relapse at 3 years of 13.0% (95% CI 0.0%-27.1%).
  • Ten patients died: 3 graft failure, 4 relapse, 2 infections (1 adenovirus, 1 toxoplasmosis), and 1 Epstein-Barr virus (EBV) lymphoproliferative disorder.
  • [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


95. Shoji N, Ito Y, Kimura Y, Nishimaki J, Kuriyama Y, Tauchi T, Yaguchi M, Payzulla D, Ebihara Y, Ohyashiki K: Pulmonary alveolar proteinosis as a terminal complication in myelodysplastic syndromes: a report of four cases detected on autopsy. Leuk Res; 2002 Jun;26(6):591-5
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  • They consisted of two refractory anemia (RA) and two patients with refractory anemia with excess blasts in transformation (RAEBt) at the time of MDS diagnosis, but all of them developed leukemic phase and were resistant to chemotherapy at the time of pulmonary episodes.


96. D'Alessandro G, Bianco MR, Politis S, Ferrandina C, Rossi G, Altomare E: [Case report: RAEB in a patient with rheumatoid arthritis treated with methotrexate and infliximab]. Reumatismo; 2006 Jan-Mar;58(1):59-61
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  • [Title] [Case report: RAEB in a patient with rheumatoid arthritis treated with methotrexate and infliximab].
  • [Transliterated title] Anemia refrattaria con eccesso di blasti (AREB) in paziente con artrite reumatoide in trattamento con methotrexate ed infliximab: descrizione di un caso clinico.
  • Anti TNF-alpha drugs seem to be the new frontier of Rheumatoid Arthritis (RA) therapy.
  • The association infliximab methotrexate has been approved for the treatment of RA not responding to the classic therapy, but the short clinical experience in using antiTNF-alpha molecules brings to segnalation of new risks or adverse events.
  • We describe a case of a patient, treated for many years with classic RA therapy, which developed a refractory anemia after treatment with association infliximab-methotrexate.
  • [MeSH-major] Anemia, Refractory, with Excess of Blasts / chemically induced. Antibodies, Monoclonal / adverse effects. Antirheumatic Agents / adverse effects. Arthritis, Rheumatoid / drug therapy. Methotrexate / adverse effects
  • [MeSH-minor] Biopsy, Fine-Needle. Bone Marrow / pathology. Drug Therapy, Combination. Female. Humans. Infliximab. Middle Aged. Tumor Necrosis Factor-alpha / antagonists & inhibitors

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  • (PMID = 16639489.001).
  • [ISSN] 0048-7449
  • [Journal-full-title] Reumatismo
  • [ISO-abbreviation] Reumatismo
  • [Language] ita
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antirheumatic Agents; 0 / Tumor Necrosis Factor-alpha; B72HH48FLU / Infliximab; YL5FZ2Y5U1 / Methotrexate
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97. Li ZL, Gong M, Xu SH, Huang FZ, Chen YR, Ma YG: [Cyclosporine A based therapy for myelodysplastic syndrome]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2005 Oct;13(5):867-70
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  • [Title] [Cyclosporine A based therapy for myelodysplastic syndrome].
  • To determine the efficacy and tolerance to cyclosporine A (CsA) based therapy in patients with myelodysplastic syndrome (MDS), 16 patients with MDS consisting of 10 refractory anemia (RA) and 6 refractory anemia with accessory blasts less than 10% (RAEB-1) were analyzed.
  • Treatment responses were classified according to the International Working Group (IWG) criteria as complete remission (CR), partial remission (PR), hematological improvement (HI) and no response (NR).
  • Response rates shown in neutrophil lineage, platelet and erythroid lineage were 83.3%, 66.7% and 60%, respectively; their shortest time required to obtain some hematologic improvement after initiation of CsA therapy was 2 weeks, 1 month and 1 month, respectively.
  • Of 13 patients being transfusion-dependent before treatment, 3 patients did not need transfusion any more and 5 showed the reduced transfusion requirements after CsA therapy.
  • Of 6 patients with RAEB, 1 patient had no response and died of RAEB-t and 5 patients had transient responses.
  • The total response rate decreased to 50% in the patients with CsA therapy lasting more than 3 months at the end of following-up.
  • In conclusion, the usefulness of CsA based therapy for MDS-RA and RAEB-1 with any marrow cellularity is useful, the CsA dose of 3-5 mg/(kg.d) is safe and efficacious.


98. Thompson JA, Gilliland DG, Prchal JT, Bennett JM, Larholt K, Nelson RA, Rose EH, Dugan MH: Effect of recombinant human erythropoietin combined with granulocyte/ macrophage colony-stimulating factor in the treatment of patients with myelodysplastic syndrome. GM/EPO MDS Study Group. Blood; 2000 Feb 15;95(4):1175-9
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  • [Title] Effect of recombinant human erythropoietin combined with granulocyte/ macrophage colony-stimulating factor in the treatment of patients with myelodysplastic syndrome. GM/EPO MDS Study Group.
  • This randomized, placebo-controlled trial was designed to assess the efficacy and safety of therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (epoetin alfa) in anemic, neutropenic patients with myelodysplastic syndrome.
  • Sixty-six patients were enrolled according to the following French-American-British classification: refractory anemia (20), refractory anemia with excess blasts (35), refractory anemia with ringed sideroblasts (9), and refractory anemia with excess blasts in transformation (2).
  • Patients were stratified by their serum erythropoietin levels (less than or equal to 500 mU/mL, n = 37; greater than 500 mU/mL, n = 29) and randomized, in a 2:1 ratio, to either GM-CSF (0.3-5.0 microg/kg.d) + epoetin alfa (150 IU/kg 3 times/wk) or GM-CSF (0.3-5.0 microg/kg.d) + placebo (3 times/wk).
  • The mean neutrophil count rose from 948 to 3831 during treatment with GM-CSF +/- epoetin alfa.
  • Treatment was well tolerated in most patients, though 10 withdrew from the study for reasons related predominantly to GM-CSF toxicity. (Blood.
  • [MeSH-major] Erythropoietin / therapeutic use. Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Anemia. Blood Transfusion. Double-Blind Method. Drug Therapy, Combination. Epoetin Alfa. Female. Humans. Male. Middle Aged. Neutropenia. Placebos. Recombinant Proteins


99. Löwenberg B, Beck J, Graux C, van Putten W, Schouten HC, Verdonck LF, Ferrant A, Sonneveld P, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, Breems D, de Muijnck H, Schaafsma R, Verhoef G, Döhner H, Gratwohl A, Pabst T, Ossenkoppele GJ, Maertens J, Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON), German Austrian AML Study Group (AMLSG), Swiss Group for Clinical Cancer Research Collaborative Group (SAKK): Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study. Blood; 2010 Apr 1;115(13):2586-91
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  • [Title] Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study.
  • In older patients with acute myeloid leukemia (AML), the prevention of relapse has remained one of the major therapeutic challenges, with more than 75% relapses after complete remission.
  • Patients with AML or refractory anemia with excess blasts in first complete remission attained after intensive induction chemotherapy were randomized between 3 cycles of GO (6 mg/m(2) every 4 weeks) or no postremission therapy (control) to assess whether GO would improve outcome.
  • The 2 treatment groups (113 patients receiving GO vs 119 control patients) were comparable with regard to age (60-78 years, median 67 years), performance status, and cytogenetics.
  • Median time to recovery of platelets 50 x 10(9)/L and neutrophils 0.5 x 10(9)/L after GO was 14 days and 20 days.
  • There were no significant differences between both treatment groups with regard to relapse probabilities, nonrelapse mortality, overall survival, or disease-free survival (17% vs 16% at 5 years).
  • Postremission treatment with GO in older AML patients does not provide benefits regarding any clinical end points.
  • The HOVON-43 study is registered at The Netherlands Trial Registry (number NTR212) and at http://www.controlled-trials.com as ISRCTN77039377.
  • [MeSH-major] Aminoglycosides / therapeutic use. Antibodies, Monoclonal / therapeutic use. Antineoplastic Agents / therapeutic use. Immunotoxins / therapeutic use. Leukemia, Myeloid / drug therapy
  • [MeSH-minor] Acute Disease. Age Factors. Aged. Anemia, Refractory, with Excess of Blasts / drug therapy. Anemia, Refractory, with Excess of Blasts / genetics. Antibodies, Monoclonal, Humanized. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Disease-Free Survival. Drug-Induced Liver Injury / etiology. Female. Fever / chemically induced. Gastrointestinal Diseases / chemically induced. Hematologic Diseases / chemically induced. Humans. Male. Middle Aged. Remission Induction. Sepsis / etiology. Survival Analysis

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  • (PMID = 20103782.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Databank-accession-numbers] ISRCTN/ ISRCTN77039377
  • [Publication-type] Clinical Trial, Phase III; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Aminoglycosides; 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antineoplastic Agents; 0 / Immunotoxins; 0 / gemtuzumab
  • [Investigator] Ferrant A; Delannoy A; Maertens J; Verhoef G; Demuynck H; Bosly A; Graux C; Breems DA; Zachee P; Jaeger E; Beck J; Fischer T; von Lilienfeld-Toal M; Glasmacher A; Hartmann F; Grimminger W; Döhner H; Bargetzi M; Wernli M; Gratwohl A; Fey MF; Pabst T; Passweg J; Chalandon Y; Herr A; Wuillemin WA; Stuessi G; Schanz U; Van Der Lelie J; Biemond BJ; De Valk B; Ossenkoppele GJ; Huijgens PC; Wijermans PW; Levin MD; Schaafsma MR; Daenen SM; Vellenga E; Voogt PJ; Schouten HC; Biesma DH; Sonneveld P; Zijlmans J; Jongen-Lavrencic M; De Greef GE; Löwenberg B; Verdonck LF; Kuball J; Van Marwijk Kooy M; Milligan DW; Pocock C; Aldouri M
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100. Hiçsönmez G, Cetin M, Yenicesu I, Olcay L, Koç A, Aktaş D, Tunçbilek E, Tuncer M: Evaluation of children with myelodysplastic syndrome: importance of extramedullary disease as a presenting symptom. Leuk Lymphoma; 2001 Aug;42(4):665-74
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Evaluation of children with myelodysplastic syndrome: importance of extramedullary disease as a presenting symptom.
  • Thirty-three children diagnosed with primary myelodysplastic syndrome (MDS) in a single institution over an 8 year period were evaluated with special emphasis on children who presented with extramedullary disease (EMD).
  • EMD was present at diagnosis in 12 (36%) of the 33 children with MDS.
  • Three patients with juvenile myelomonocytic leukemia (JMML) and 2 patients with chronic myelomonocytic leukemia (CMML) presented with pleural effusion.
  • Lymphadenopathy (n=1), gingival hypertrophy (n=2), orbital granulocytic sarcoma (n=1) and spinal mass (n=1) were the presenting findings in 5 patients with refractory anemia with excess of blasts in transformation.
  • Since high-dose methylprednisolone (HDMP, 20-30 mg/kg/day) has been shown to induce differentiation and apoptosis of myeloid leukemic cells in children with different morphological subtypes of acute myeloid leukemia in vivo and in vitro, 25 children with de novo MDS were treated with combined HDMP and cytotoxic chemotherapy.
  • Dramatic improvement of EMD and decrease in blast cells both in the peripheral blood and bone marrow were obtained following administration of short-course HDMP treatment alone as observed in children with AML.
  • In conclusion EMD can be a presenting finding in childhood MDS as observed in adults.
  • In addition, the beneficial effect of HDMP combined with more intensive chemotherapy should be explored as alternative therapy in children with MDS not suitable for bone marrow transplantation.
  • [MeSH-major] Myelodysplastic Syndromes / drug therapy. Myelodysplastic Syndromes / pathology
  • [MeSH-minor] Adolescent. Anti-Inflammatory Agents / administration & dosage. Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Child. Child, Preschool. Diagnosis, Differential. Female. Humans. Infant. Leukemia, Myelomonocytic, Chronic / diagnosis. Leukemia, Myelomonocytic, Chronic / drug therapy. Male. Methylprednisolone / administration & dosage. Prospective Studies. Remission Induction. Sarcoma, Myeloid / diagnosis. Sarcoma, Myeloid / drug therapy. Treatment Outcome






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