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1. Fizazi K, Prow DM, Do KA, Wang X, Finn L, Kim J, Daliani D, Papandreou CN, Tu SM, Millikan RE, Pagliaro LC, Logothetis CJ, Amato RJ: Alternating dose-dense chemotherapy in patients with high volume disseminated non-seminomatous germ cell tumours. Br J Cancer; 2002 May 20;86(10):1555-60
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  • [Title] Alternating dose-dense chemotherapy in patients with high volume disseminated non-seminomatous germ cell tumours.
  • The aim of this phase II study was to assess the efficacy and toxicity of a dose-dense alternating chemotherapy regimen in this subset of patients.
  • Patients received a median of 2.5 courses (range 0.25 to five courses) of the BOP-CISCA-POMB-ACE regimen.
  • Forty-two patients (72.4%) had a complete response to therapy.
  • With a median follow-up time of 31 months, the 3-year progression-free survival rate was 71% (95% confidence interval, 60 to 84%) and the 3-year overall survival rate was 73% (95% confidence interval: 62 to 86%).
  • Early side effects included mainly grade 4 haematologic toxicity (neutropaenia in 79% of patients, thrombocytopaenia in 69%, anaemia in 22%), grade 4 stomatitis (19%), and four early deaths (7% of patients), at least partially related to toxicity.
  • Because outcomes with this regimen compare favourably with outcome after standard therapy, dose-dense chemotherapy should be further investigated in this subset of patients.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Germinoma / drug therapy. Seminoma / drug therapy. Testicular Neoplasms / drug therapy
  • [MeSH-minor] Adolescent. Adult. Anemia, Refractory, with Excess of Blasts / chemically induced. Biomarkers, Tumor / blood. Bleomycin / administration & dosage. Bleomycin / adverse effects. Cisplatin / administration & dosage. Cisplatin / adverse effects. Cyclophosphamide / administration & dosage. Cyclophosphamide / adverse effects. Dactinomycin / administration & dosage. Dactinomycin / adverse effects. Disease-Free Survival. Doxorubicin / administration & dosage. Doxorubicin / adverse effects. Etoposide / administration & dosage. Etoposide / adverse effects. Gastrointestinal Diseases / chemically induced. Hematologic Diseases / chemically induced. Humans. Lung Neoplasms / drug therapy. Lung Neoplasms / secondary. Male. Methotrexate / administration & dosage. Methotrexate / adverse effects. Middle Aged. Peripheral Nervous System Diseases / chemically induced. Prognosis. Prospective Studies. Remission Induction. Survival Analysis. Survival Rate. Treatment Outcome. Vincristine / administration & dosage. Vincristine / adverse effects

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  • [Copyright] comCopyright 2002 Cancer Research UK
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  • (PMID = 12085204.001).
  • [ISSN] 0007-0920
  • [Journal-full-title] British journal of cancer
  • [ISO-abbreviation] Br. J. Cancer
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article
  • [Publication-country] Scotland
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 11056-06-7 / Bleomycin; 1CC1JFE158 / Dactinomycin; 5J49Q6B70F / Vincristine; 6PLQ3CP4P3 / Etoposide; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; Q20Q21Q62J / Cisplatin; YL5FZ2Y5U1 / Methotrexate; BOP-CISCA-POMB-ACE regimen
  • [Other-IDs] NLM/ PMC2746595
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2. Deeg HJ, Gotlib J, Beckham C, Dugan K, Holmberg L, Schubert M, Appelbaum F, Greenberg P: Soluble TNF receptor fusion protein (etanercept) for the treatment of myelodysplastic syndrome: a pilot study. Leukemia; 2002 Feb;16(2):162-4
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  • [Title] Soluble TNF receptor fusion protein (etanercept) for the treatment of myelodysplastic syndrome: a pilot study.
  • Therefore, we enrolled 14 MDS patients (4 RA, 2 RARS, 6 RAEB, 2 CMML), 44-80 (median 60) years old, in a pilot trial.
  • Etanercept, 25 mg, was given twice a week s.c. for 16 weeks (increased to three times a week if no response at 8 weeks).
  • Thus, etanercept treatment resulted in moderate improvements of cytopenias in some patients, while cell counts declined in others.
  • [MeSH-major] Immunoglobulin G / therapeutic use. Myelodysplastic Syndromes / drug therapy. Receptors, Tumor Necrosis Factor / therapeutic use
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Blood Cell Count. Blood Transfusion. Bone Marrow / pathology. Combined Modality Therapy. Etanercept. Female. Humans. Male. Middle Aged. Pilot Projects. Treatment Outcome. Tumor Necrosis Factor-alpha / analysis

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  • (PMID = 11840280.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA87948; United States / NHLBI NIH HHS / HL / HL36444
  • [Publication-type] Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Immunoglobulin G; 0 / Receptors, Tumor Necrosis Factor; 0 / Tumor Necrosis Factor-alpha; OP401G7OJC / Etanercept
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3. Ten Oever J, Kuijper PH, Kuijpers AL, Dercksen MW, Vreugdenhil G: Complete remission of MDS RAEB following immunosuppressive treatment in a patient with Sweet's syndrome. Neth J Med; 2009 Sep;67(8):347-50
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  • [Title] Complete remission of MDS RAEB following immunosuppressive treatment in a patient with Sweet's syndrome.
  • We report on a patient with myelodysplastic syndrome (MDS), classified as refractory anaemia with excess of blasts-2, and histiocytoid Sweet's syndrome.
  • Inhibition of T-cell mediated myelosuppression by corticosteroids or a proapoptotic effect of doxycycline may have attributed as well.
  • [MeSH-major] Adrenal Cortex Hormones / therapeutic use. Anemia, Refractory, with Excess of Blasts / drug therapy. Anti-Bacterial Agents / therapeutic use. Doxycycline / therapeutic use. Immunosuppressive Agents / therapeutic use. Sweet Syndrome / complications
  • [MeSH-minor] Aged. Fatal Outcome. Humans. Killer Cells, Natural. Male. Recurrence. Remission Induction. Treatment Outcome

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  • (PMID = 19767665.001).
  • [ISSN] 1872-9061
  • [Journal-full-title] The Netherlands journal of medicine
  • [ISO-abbreviation] Neth J Med
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Adrenal Cortex Hormones; 0 / Anti-Bacterial Agents; 0 / Immunosuppressive Agents; N12000U13O / Doxycycline
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4. 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

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


6. 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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  • 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.
  • [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


7. Ravoet C, Mineur P, Robin V, Debusscher L, Bosly A, André M, El Housni H, Soree A, Bron D, Martiat P: Farnesyl transferase inhibitor (lonafarnib) in patients with myelodysplastic syndrome or secondary acute myeloid leukaemia: a phase II study. Ann Hematol; 2008 Nov;87(11):881-5
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  • [Title] Farnesyl transferase inhibitor (lonafarnib) in patients with myelodysplastic syndrome or secondary acute myeloid leukaemia: a phase II study.
  • Lonafarnib was administered orally at a dose of 200 mg twice daily for three courses of 4 weeks (separated by 1 to 4 weeks without treatment).
  • Sixteen patients were included: FAB/RAEB (n = 10), RAEB-T (n = 2), sAML (n = 2) and chronic myelomonocytic leukaemia (CMML; n = 2); WHO/RAEB-1 (n = 4), RAEB-2 (n = 5), AML (n = 5), CMML (n = 2).
  • One patient died of infection, and the treatment was stopped in one other who developed atrial fibrillation.
  • [MeSH-major] Farnesyltranstransferase / antagonists & inhibitors. Leukemia, Myeloid, Acute / drug therapy. Myelodysplastic Syndromes / drug therapy. Piperidines / adverse effects. Pyridines / adverse effects


8. Pawson R, Potter MN, Theocharous P, Lawler M, Garg M, Yin JA, Rezvani K, Craddock C, Rassam S, Prentice HG: Treatment of relapse after allogeneic bone marrow transplantation with reduced intensity conditioning (FLAG +/- Ida) and second allogeneic stem cell transplant. Br J Haematol; 2001 Dec;115(3):622-9
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  • [Title] Treatment of relapse after allogeneic bone marrow transplantation with reduced intensity conditioning (FLAG +/- Ida) and second allogeneic stem cell transplant.
  • Fludarabine-containing 'non-myeloablative' chemotherapy followed by further allo SCT may offer more rapid and effective disease control.
  • We report 14 patients with relapse after allo SCT for acute leukaemia [seven acute myeloid leukaemia (AML), five acute lymphoblastic leukaemia (ALL)] or refractory anaemia with excess blasts in transformation (RAEB-t, n = 2) treated with fludarabine, high-dose cytosine arabinoside (ara-C) and granulocyte colony-simulating factor (G-CSF) with (n = 10) or without (n = 2) idarubicin (FLAG +/- Ida) or DaunoXome (FLAG-X) (n = 2) and second allo SCT from the original donor.
  • Transplants were well tolerated with no treatment-related deaths.
  • 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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9. 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).
  • 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

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  • (PMID = 17199984.001).
  • [ISSN] 0376-2491
  • [Journal-full-title] Zhonghua yi xue za zhi
  • [ISO-abbreviation] Zhonghua Yi Xue Za Zhi
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Immunosuppressive Agents; 83HN0GTJ6D / Cyclosporine
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10. Shimamoto T, Tohyama K, Okamoto T, Uchiyama T, Mori H, Tomonaga M, Asano Y, Niho Y, Teramura M, Mizoguchi H, Omine M, Ohyashiki K: Cyclosporin A therapy for patients with myelodysplastic syndrome: multicenter pilot studies in Japan. Leuk Res; 2003 Sep;27(9):783-8
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  • [Title] Cyclosporin A therapy for patients with myelodysplastic syndrome: multicenter pilot studies in Japan.
  • We examined the efficacy of cyclosporin A (CsA) in 50 patients with myelodysplastic syndrome (MDS) consisting from 47 of RA, 1 of RARS, and 2 of RAEB.
  • These patients showed various marrow cell types including hypo-, normo-, and hypercellularity.
  • The median CsA dose was 4.58mg/kg, and treatment responses were classified according to the International Working Group (IWG) criteria.
  • In the patients with RARS or RAEB, no efficacy was observed.
  • When we analyzed the correlation between the response to CsA therapy and the karyotype or HLA type, there were significantly more responders with good karyotype or DRB1*1501 than with intermediate/poor karyotypes or with other HLA types.
  • These results indicate the usefulness of CsA therapy for MDS patients with any marrow cellularity, especially for erythroid lineage and patients with good karyotype or DRB1*1501.
  • [MeSH-major] Cyclosporine / therapeutic use. Immunosuppressive Agents / therapeutic use. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Anemia, Refractory / blood. Anemia, Refractory / drug therapy. Anemia, Refractory, with Excess of Blasts / blood. Anemia, Refractory, with Excess of Blasts / drug therapy. Blood Platelets / chemistry. Bone Marrow / pathology. Cell Lineage. Drug Evaluation. Erythrocytes / chemistry. Female. Humans. Japan. Karyotyping. Male. Middle Aged. Neutrophils / chemistry. Pilot Projects. Treatment Outcome


11. 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.
  • 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


12. Abe Y, Muta K, Hirase N, Choi I, Matsushima T, Hara K, Taguchi F, Suematsu E, Shibata K, Uike N, Nishimura J, Nawata H: [Vitamin K2 therapy for myelodysplastic syndrome]. Rinsho Ketsueki; 2002 Feb;43(2):117-21
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  • [Title] [Vitamin K2 therapy for myelodysplastic syndrome].
  • We administered a vitamin K2 analog, menatetrenone, at 45 mg daily to 23 patients with myelodysplastic syndrome (MDS): 13 patients with RA, 2 with RARS, 6 with RAEB and 2 with RAEB-T.
  • Six of the RA patients showed improvement of anemia (GR, 3 patients; PR, 3 patients).
  • RA patients who did not have a hypocellular bone marrow and were transfusion-independent tended to be responsive to vitamin K2 therapy in combination with vitamin D3 or anabolic steroids.
  • No adverse effect of vitamin K2 was observed, and the time required to obtain the hematological response was short, being 3 months on average.
  • We believe that vitamin K2 therapy has potential as a treatment for patients with MDS.
  • [MeSH-major] Myelodysplastic Syndromes / drug therapy. Vitamin K 2 / therapeutic use
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Drug Administration Schedule. Female. Humans. Male. Middle Aged

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  • (PMID = 11925874.001).
  • [ISSN] 0485-1439
  • [Journal-full-title] [Rinshō ketsueki] The Japanese journal of clinical hematology
  • [ISO-abbreviation] Rinsho Ketsueki
  • [Language] jpn
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 11032-49-8 / Vitamin K 2
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13. 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


14. Kokhno AV, Savchenko VG, Parovichnikova EN, Kharazishvili DI, Sokolovskaia AA, Lukashina MI, Baryshnikov AIu: [Apoptosis and proliferative activity of bone marrow cells in patients with aplastic syndromes as evidenced by trephine biopsy]. Ter Arkh; 2001;73(7):51-6
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  • MATERIALS AND METHODS: The TUNEL immunohistochemical assay was used to study apoptosis of bone marrow cells in the histological specimens from 24 patients: 8 with refractory anemia (RA), 8 with acute small-proportion leukemias [RA with excessive blasts (RAEB) + RAEB in transformation (RAEBt)], 3 with acute non-lymphoblastic leukemia (ANLL), 5 with lymphogranulomatosis (LGM).
  • The proliferative activity of bone marrow cell was evaluated by bone marrow histological specimens from 10 patients (8 patients with RA and 2 with RAEB + RAEBt) at the onset of disease and during CSA therapy in the immunohistochemical test with primary nuclear antigen Ki-67 antigen antibodies.
  • [MeSH-major] Anemia, Refractory / drug therapy. Apoptosis. Bone Marrow Cells / drug effects. Cyclosporine / pharmacology. Immunosuppressive Agents / pharmacology. Leukemia / drug therapy

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  • (PMID = 11523410.001).
  • [ISSN] 0040-3660
  • [Journal-full-title] Terapevticheskiĭ arkhiv
  • [ISO-abbreviation] Ter. Arkh.
  • [Language] rus
  • [Publication-type] Comparative Study; English Abstract; Journal Article
  • [Publication-country] Russia
  • [Chemical-registry-number] 0 / Immunosuppressive Agents; 83HN0GTJ6D / Cyclosporine
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15. Jackson G, Taylor P, Smith GM, Marcus R, Smith A, Chu P, Littlewood TJ, Duncombe A, Hutchinson M, Mehta AB, Johnson SA, Carey P, MacKie MJ, Ganly PS, Turner GE, Deane M, Schey S, Brookes J, Tollerfield SM, Wilson MP: A multicentre, open, non-comparative phase II study of a combination of fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor in relapsed and refractory acute myeloid leukaemia and de novo refractory anaemia with excess of blasts in transformation. Br J Haematol; 2001 Jan;112(1):127-37
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  • [Title] A multicentre, open, non-comparative phase II study of a combination of fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor in relapsed and refractory acute myeloid leukaemia and de novo refractory anaemia with excess of blasts in transformation.
  • The primary objective of this study was to determine the complete remission (CR) rate achieved with the FLAG (fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor) regimen in patients with relapsed or refractory acute myeloid leukaemia (AML) or de novo refractory anaemia with excess of blasts in transformation (RAEB-t).
  • Induction treatment consisted of between one and two courses of FLAG.
  • Patients achieving CR received between one and two courses of consolidation treatment.
  • CR rates were: 17 out of 21 (81%) in late relapse AML (Group 1), 13 out of 44 (30%) in early relapse/refractory AML (Group 2), and 10 out of 18 (56%) in de novo RAEB-t (Group 3).
  • Median survival times were 1.4 years, 3 months and 1.6 years in Groups 1, 2 and 3 respectively.
  • The FLAG regimen offers a very effective alternative treatment for CR induction in poor prognosis adult patients with either relapsed or refractory AML or de novo RAEB-t.
  • FLAG delivers high-dose treatment without increasing overall toxicity, an approach which is of particular value in older patients, who constitute the majority in these diseases.
  • It is therefore an important advance in developing new treatment options for these patients.
  • [MeSH-major] Anemia, Refractory, with Excess of Blasts / drug therapy. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Myeloid / drug therapy

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  • (PMID = 11167793.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article; Multicenter Study
  • [Publication-country] England
  • [Chemical-registry-number] 04079A1RDZ / Cytarabine; 143011-72-7 / Granulocyte Colony-Stimulating Factor; FA2DM6879K / Vidarabine; FLAG protocol
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16. Strupp C, Knipp S, Hartmann J, Gattermann N, Haas R, Germing U: A pilot study of bendamustine in elderly patients with high-risk MDS and AML. Leuk Lymphoma; 2007 Jun;48(6):1161-6
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  • We examined the efficacy of bendamustine in 15 pretreated patients (12 men, 3 women, median age 69 years) with acute myeloid leukaemia (AML) or myelodysplastic syndromes (MDS) 3 AML, 5 sAML, 5 CMML II, 1 RAEB II.
  • Nine of 15 patients had no side effects of the treatment, six patients suffered from vomiting and epigastric pain as adverse effects of bendamustine.
  • In summary, treatment with bendamustine in patients with high-risk MDS or sAML with leukocytosis can result in a significant reduction of leukocytes, but fails to achieve hematological responses or improvement of transfusions dependency.
  • [MeSH-major] Leukemia, Myeloid / drug therapy. Myelodysplastic Syndromes / drug therapy. Nitrogen Mustard Compounds / therapeutic use
  • [MeSH-minor] Acute Disease. Aged. Antineoplastic Agents / adverse effects. Antineoplastic Agents / therapeutic use. Bendamustine Hydrochloride. Drug Evaluation. Female. Humans. Male. Pilot Projects

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  • [CommentIn] Leuk Lymphoma. 2007 Jun;48(6):1064-6 [17577766.001]
  • (PMID = 17577779.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Evaluation Studies; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Nitrogen Mustard Compounds; 981Y8SX18M / Bendamustine Hydrochloride
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17. 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


18. 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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  • [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.


19. Guan M, Chen SC, Li RS, Ge CW, Zhu HL: [Low dose all-trans retinoic acid and androgen therapy for patients with myelodysplastic syndrome]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2004 Dec;12(6):774-8
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  • [Title] [Low dose all-trans retinoic acid and androgen therapy for patients with myelodysplastic syndrome].
  • To explore therapeutic efficacy of androgens and low dose all-trans retinoic acid (ATRA) for myelodysplastic syndrome (MDS) patients, 55 patients of MDS were observed, including 41 cases of refractory anemia (RA), 11 cases of refractory anemia with excess of blasts (RAEB), 2 cases of refractory anemia with excess of blasts in transformation (RAEB-t) and 1 case of chronic myeloic-monocytic leukemia (CMML).
  • In conclusion, danazol or stanazol in combination with low dose ATRA are partialy effective in therapy for patients with low-risk myelodysplastic syndrome.

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  • (PMID = 15631659.001).
  • [ISSN] 1009-2137
  • [Journal-full-title] Zhongguo shi yan xue ye xue za zhi
  • [ISO-abbreviation] Zhongguo Shi Yan Xue Ye Xue Za Zhi
  • [Language] CHI
  • [Publication-type] English Abstract; Journal Article; Randomized Controlled Trial
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Androgens; 0 / Antineoplastic Agents; 5688UTC01R / Tretinoin
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20. Honda Y, Manabe A, Tsuchida M, Zaike Y, Masunaga A, Inoue M, Kobayashi R, Ohtsuka Y, Kikuchi A, Nakahata T, MDS Committee, the Japanese Society of Pediatric Hematology: Clinicopathological characteristics of erythroblast-rich RAEB and AML M6a in children. Int J Hematol; 2008 Dec;88(5):524-9
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  • [Title] Clinicopathological characteristics of erythroblast-rich RAEB and AML M6a in children.
  • The distinction between RAEB, RAEB-T and AML M6a is difficult when erythroblasts in the bone marrow (BM) exceed 50%.
  • We analyzed 19 children (2 RAEB, 13 RAEB-T and 4 AML M6a) enrolled in a prospective pathological central review in Japan and divided them into two groups according to the myeloblasts percentage among non-erythroid cells in BM: group A (n = 8), 5-19% myeloblasts; group B (n = 11), 20% or more myeloblasts.
  • Six with group A and seven with group B treated with AML type chemotherapy achieved complete remission.
  • Five with group A and seven with group B undergoing SCT are alive at a median of 3 years after diagnosis.
  • Erythroblast-rich RAEB and AML M6a in children have similar characteristics and may belong to a single disease entity.
  • [MeSH-major] Anemia, Refractory, with Excess of Blasts / pathology. Erythroblasts / pathology. Granulocyte Precursor Cells / pathology. Leukemia, Myeloid, Acute / pathology
  • [MeSH-minor] Adolescent. Child. Child, Preschool. Female. Humans. Infant. Japan. Leukocyte Count. Male. Prospective Studies. Remission Induction. Stem Cell Transplantation. Time Factors. Transplantation, Homologous

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  • (PMID = 18951200.001).
  • [ISSN] 1865-3774
  • [Journal-full-title] International journal of hematology
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  • [Publication-type] Journal Article; Multicenter Study
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21. 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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22. 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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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [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

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  • (PMID = 12592329.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Phytogenic; 7673326042 / irinotecan; XT3Z54Z28A / Camptothecin
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23. Hofmann WK, Kell WJ, Fenaux P, Castaigne S, Ganser A, Chomienne C, Burnett R, Kowal C, Hoelzer D, Burnett AK: Oral 9-cis retinoic acid (Alitretinoin) in the treatment of myelodysplastic syndromes: results from a pilot study. Leukemia; 2000 Sep;14(9):1583-8
The Lens. Cited by Patents in .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Oral 9-cis retinoic acid (Alitretinoin) in the treatment of myelodysplastic syndromes: results from a pilot study.
  • A multicenter phase II study was initiated to investigate the efficacy, toxicity and tolerability of an oral regimen of 9-cis retinoic acid (9CRA) as a differentiation-inducing agent stimulating both retinoic acid receptor (RAR) and retinoic X receptor (RXR).
  • The MDS subtypes were distributed as follows: 14 refractory anaemia (RA), four refractory anaemia with ringed sideroblasts (RARS), and 12 refractory anaemia with excess blasts (RAEB).
  • None of these had previously received treatment for MDS other than supportive therapy.
  • 9CRA (Alitretinoin capsules, kindly provided by Allergan-Ligand Retinoid Therapeutics) was given daily at 60 mg/m2 p.o. for 1 week, followed by an intra-patient escalation to 100 mg/m2 during the second week, up to a maximum of 140 mg/m2.
  • The planned treatment duration was 48 weeks.
  • Four (16%), two with RA, two with RAEB, had minor responses resulting in decreased transfusion requirements or increased neutrophils.
  • In conclusion, although modest responses were noted in this study, the treatment tolerability was suboptimal.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Myelodysplastic Syndromes / drug therapy. Tretinoin / therapeutic use
  • [MeSH-minor] Administration, Oral. Adult. Aged. Aged, 80 and over. Blood Transfusion. Female. Hematopoiesis. Humans. Male. Middle Aged. Pilot Projects. Treatment Outcome






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