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1. Ziarkiewicz M, Dwilewicz-Trojaczek J, Pastwińska A, Chmarzyńska E, Paszkowska-Kowalewska M, Koperski Ł, Jędrzejczak WW, Ziarkiewicz-Wróblewska B: Refractory anaemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T) with superimposed 5q-syndrome. Pol J Pathol; 2010;61(2):105-9
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  • [Title] Refractory anaemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T) with superimposed 5q-syndrome.
  • Refractory anaemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T) is a rare entity belonging to myeloproliferative/myelodysplastic syndromes.
  • Herein we describe a 69-year-old male with anaemia and thrombocytosis presenting with coexisting features of both these rare diseases.
  • After the description of the clinical data, we summarize the histopathologic, cytogenetic and molecular findings, as well as introduced treatment.
  • [MeSH-major] Anemia, Refractory / pathology. Anemia, Sideroblastic / pathology. Thrombocytosis / pathology
  • [MeSH-minor] Aged. Anemia, Macrocytic / drug therapy. Anemia, Macrocytic / genetics. Anemia, Macrocytic / pathology. Antineoplastic Agents / therapeutic use. Bone Marrow Cells / pathology. Chromosome Deletion. Chromosomes, Human, Pair 5 / genetics. Drug Therapy, Combination. Humans. Hydroxyurea / therapeutic use. In Situ Hybridization, Fluorescence. Male. Thalidomide / analogs & derivatives. Thalidomide / therapeutic use

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  • (PMID = 20924996.001).
  • [ISSN] 1233-9687
  • [Journal-full-title] Polish journal of pathology : official journal of the Polish Society of Pathologists
  • [ISO-abbreviation] Pol J Pathol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Poland
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 4Z8R6ORS6L / Thalidomide; F0P408N6V4 / lenalidomide; X6Q56QN5QC / Hydroxyurea; Chromosome 5q Deletion Syndrome
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2. Huls G, Mulder AB, Rosati S, van de Loosdrecht AA, Vellenga E, de Wolf JT: Efficacy of single-agent lenalidomide in patients with JAK2 (V617F) mutated refractory anemia with ring sideroblasts and thrombocytosis. Blood; 2010 Jul 15;116(2):180-2
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  • [Title] Efficacy of single-agent lenalidomide in patients with JAK2 (V617F) mutated refractory anemia with ring sideroblasts and thrombocytosis.
  • Patients with refractory anemia with ring sideroblasts and thrombocytosis (RARS-T) are difficult to treat because the cytoreductive treatment might be beneficial for the thrombocytosis component but harmful for the RARS component.
  • We report the results of lenalidomide treatment in these patients and show that lenalidomide has clinical activity in this rare disorder.
  • [MeSH-major] Anemia, Refractory / drug therapy. Anemia, Sideroblastic / drug therapy. Antineoplastic Agents / therapeutic use. Janus Kinase 2 / genetics. Thalidomide / analogs & derivatives. Thrombocytosis / drug therapy
  • [MeSH-minor] Aged, 80 and over. Anabolic Agents / therapeutic use. Erythropoietin / therapeutic use. Humans. Hypertension, Pulmonary / complications. Male. Middle Aged. Mutation. Pulmonary Embolism / complications. Pyridoxine / therapeutic use. Reverse Transcriptase Polymerase Chain Reaction. Vitamin B Complex / therapeutic use

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  • (PMID = 20194893.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Anabolic Agents; 0 / Antineoplastic Agents; 11096-26-7 / Erythropoietin; 12001-76-2 / Vitamin B Complex; 4Z8R6ORS6L / Thalidomide; EC 2.7.10.2 / Janus Kinase 2; F0P408N6V4 / lenalidomide; KV2JZ1BI6Z / Pyridoxine
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3. Bunworasate U, Arnouk H, Minderman H, O'Loughlin KL, Sait SN, Barcos M, Stewart CC, Baer MR: Erythropoietin-dependent transformation of myelodysplastic syndrome to acute monoblastic leukemia. Blood; 2001 Dec 1;98(12):3492-4
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  • Acute monoblastic leukemia (acute myeloid leukemia [AML], French-American-British type M5a) with leukemia cutis developed in a patient 6 weeks after the initiation of erythropoietin (EPO) therapy for refractory anemia with ringed sideroblasts.
  • [MeSH-minor] Aged. Anemia, Sideroblastic / drug therapy. Anemia, Sideroblastic / pathology. Antigens, CD13 / analysis. Antigens, CD45 / analysis. Bone Marrow / pathology. Flow Cytometry. Humans. Male. Receptors, Erythropoietin / analysis. Skin / pathology


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4. 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.
  • 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.

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  • (PMID = 11960342.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] England
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5. Chen S, Jiang B, Da W, Gong M, Guan M: Treatment of myelodysplastic syndrome with cyclosporin A. Int J Hematol; 2007 Jan;85(1):11-7
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  • [Title] Treatment of myelodysplastic syndrome with cyclosporin A.
  • The FAB subtypes of the patients included refractory anemia, refractory anemia with ringed sideroblasts, and refractory anemia with excess blasts.
  • The drug was administered twice a day for more than 3 months.
  • After 3 months of treatment, hematological improvement was observed in 18 of 32 patients (56.3%) by the criteria of the International Working Group.
  • At the end of the follow-up (median time, 14 months), 4 patients showed alteration of disease progression, including 1 complete remission and 3 partial remissions, and 16 patients showed hematological improvement.
  • It was shown that the CsA therapy was effective in patients with refractory anemia or refractory anemia with excess blasts and both hypo- and hyperplastic bone marrows might respond to the therapy.
  • The survival time was significantly longer in responders than in nonresponders.
  • The study shows that CsA therapy is potentially the most effective therapy for myelodysplastic syndromes.
  • [MeSH-major] Cyclosporine / administration & dosage. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Anemia, Refractory / drug therapy. Anemia, Refractory, with Excess of Blasts / drug therapy. Anemia, Sideroblastic / drug therapy. Bone Marrow / pathology. Child. Female. Humans. Male. Middle Aged. Remission Induction. Survival Rate. Treatment Outcome

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  • (PMID = 17261496.001).
  • [ISSN] 0925-5710
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] Japan
  • [Chemical-registry-number] 83HN0GTJ6D / Cyclosporine
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6. Tehranchi R, Fadeel B, Schmidt-Mende J, Forsblom AM, Emanuelsson E, Jadersten M, Christensson B, Hast R, Howe RB, Samuelsson J, Zhivotovsky B, Hellström-Lindberg E: Antiapoptotic role of growth factors in the myelodysplastic syndromes: concordance between in vitro and in vivo observations. Clin Cancer Res; 2005 Sep 1;11(17):6291-9
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  • In the present study, we compared the in vitro and in vivo effects of proerythroid treatment with erythropoietin + granulocyte colony-stimulating factor (G-CSF) on myelodysplastic erythropoiesis regarding apoptosis and preferential growth of clones with cytogenetic abnormalities.
  • EXPERIMENTAL DESIGN: We enrolled 15 refractory anemia (RA) and 11 refractory anemia with ringed sideroblasts (RARS), including 5q- aberration, monosomy 7, and trisomy 8, before initiation of treatment and followed nine patients after successful treatment.
  • RESULTS: Significant redistribution of cytochrome c was seen before treatment at all stages of erythroid differentiation.
  • [MeSH-major] Anemia, Refractory / drug therapy. Anemia, Sideroblastic / drug therapy. Apoptosis / drug effects. Erythroid Precursor Cells / drug effects
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Bone Marrow Cells / cytology. Bone Marrow Cells / metabolism. Caspases / metabolism. Cytochromes c / metabolism. Enzyme Activation / drug effects. Erythropoietin / pharmacology. Glycophorin / metabolism. Granulocyte Colony-Stimulating Factor / pharmacology. Humans. In Vitro Techniques. Middle Aged. Monosomy. Receptors, Granulocyte Colony-Stimulating Factor / metabolism. Recombinant Proteins. Trisomy

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  • (PMID = 16144933.001).
  • [ISSN] 1078-0432
  • [Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research
  • [ISO-abbreviation] Clin. Cancer Res.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Glycophorin; 0 / Receptors, Granulocyte Colony-Stimulating Factor; 0 / Recombinant Proteins; 11096-26-7 / Erythropoietin; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 9007-43-6 / Cytochromes c; EC 3.4.22.- / Caspases
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7. Raza A, Meyer P, Dutt D, Zorat F, Lisak L, Nascimben F, du Randt M, Kaspar C, Goldberg C, Loew J, Dar S, Gezer S, Venugopal P, Zeldis J: Thalidomide produces transfusion independence in long-standing refractory anemias of patients with myelodysplastic syndromes. Blood; 2001 Aug 15;98(4):958-65
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  • [Title] Thalidomide produces transfusion independence in long-standing refractory anemias of patients with myelodysplastic syndromes.
  • Thirty-two patients stopped therapy before 12 weeks (minimum period for response evaluation), and 51 completed 12 weeks of therapy.
  • Off-study patients belonged to a higher risk category (P =.002) and had a higher percentage of blasts in their pretherapy bone marrow than patients who completed 12 weeks of therapy (P =.003).
  • Among responders, 9 had refractory anemia (RA); 5 had RA with ringed sideroblasts; and 2 had RA with excess blasts.
  • [MeSH-major] Anemia / drug therapy. Blood Transfusion. Myelodysplastic Syndromes / drug therapy. Thalidomide / pharmacology
  • [MeSH-minor] Aged. Blood Cell Count. Bone Marrow / drug effects. Bone Marrow / pathology. Female. Hematopoiesis / drug effects. Hemoglobins / metabolism. Humans. Male. Maximum Tolerated Dose. Pilot Projects. Treatment Outcome


8. 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


9. Yağci M, Sucak GT, Oğur G, Haznedar R: Therapy-related refractory anemia with ringed sideroblasts in chronic lymphocytic leukemia. involvement of 3q21 region. Cancer Genet Cytogenet; 2001 Aug;129(1):43-6
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  • [Title] Therapy-related refractory anemia with ringed sideroblasts in chronic lymphocytic leukemia. involvement of 3q21 region.
  • Therapy-related myelodysplastic syndrome/acute myelogenous leukemia (t-MDS/AML) is extremely rare in chronic lymphocytic leukemia (CLL) despite extensive use of alkylating agents.
  • We present a case of heavily treated CLL with resultant therapy-related refractory anemia with ringed sideroblasts (RARS).
  • A complex cytogenetic abnormality including involvement of 3q21 was detected and to our knowledge, is the first report of a RARS case with a 3q21 abnormality.
  • [MeSH-major] Anemia, Refractory / genetics. Chromosome Aberrations. Chromosomes, Human, Pair 3. Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy. Leukemia, Myeloid, Acute / genetics. Neoplasms, Second Primary / genetics


10. Schmitt-Graeff AH: [Chronic myeloid neoplasms. Diagnostic criteria and current therapeutic concepts]. Pathologe; 2010 Feb;31(1):29-41
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  • [Title] [Chronic myeloid neoplasms. Diagnostic criteria and current therapeutic concepts].
  • Myelodysplastic/MPN overlap syndromes include rare entities such as refractory anemia with ringed sideroblasts characterized by a high proportion of JAK2V617F mutated cases.
  • The paradigm of targeted treatment of chronic myeloid leukemia with imatinib has now been extended to eosinophilia-associated myeloid neoplasms with PDGFRA, PDGFRB or FGFR1 gene mutations.
  • JAK2 inhibitor drugs are currently being tested in clinical trials.
  • The development of pathogenesis-targeted diagnostic and therapeutic approaches to the various MPNs will continue in the future.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • [MeSH-minor] Alleles. Biomarkers, Tumor / genetics. Bone Marrow / pathology. DNA Mutational Analysis. Diagnosis, Differential. Humans. Leukemia, Myelomonocytic, Chronic / drug therapy. Leukemia, Myelomonocytic, Chronic / genetics. Leukemia, Myelomonocytic, Chronic / pathology. Molecular Diagnostic Techniques. Myeloproliferative Disorders / drug therapy. Myeloproliferative Disorders / genetics. Myeloproliferative Disorders / pathology. Polycythemia Vera / drug therapy. Polycythemia Vera / genetics. Polycythemia Vera / pathology. Primary Myelofibrosis / drug therapy. Primary Myelofibrosis / genetics. Primary Myelofibrosis / pathology. Prognosis. Protein-Tyrosine Kinases / antagonists & inhibitors. Signal Transduction / drug effects. Signal Transduction / genetics


11. Terpos E, Mougiou A, Kouraklis A, Chatzivassili A, Michalis E, Giannakoulas N, Manioudaki E, Lazaridou A, Bakaloudi V, Protopappa M, Liapi D, Grouzi E, Parharidou A, Symeonidis A, Kokkini G, Laoutaris NP, Vaipoulos G, Anagnostopoulos NI, Christakis JI, Meletis J, Bourantas KL, Zoumbos NC, Yataganas X, Viniou NA, Greek MDS Study Group: Prolonged administration of erythropoietin increases erythroid response rate in myelodysplastic syndromes: a phase II trial in 281 patients. Br J Haematol; 2002 Jul;118(1):174-80
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  • Treatment with recombinant human erythropoietin (rHuEpo) improves anaemia in approximately 20% of patients with myelodysplastic syndromes (MDS).
  • We investigated the potential advantage of a prolonged administration of rHuEpo to achieve higher erythroid response rates (RR) in 281 MDS patients: 118 with refractory anaemia (RA), 77 with refractory anaemia and ringed sideroblasts (RARS), 59 with refractory anaemia with excess of blasts and blast count < 10% (RAEB-I), and 27 with RAEB and blast count between 11-20% (RAEB-II).
  • Response to treatment was evaluated after 12 and 26 weeks of therapy.
  • 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


12. Lyons RM, Cosgriff TM, Modi SS, Gersh RH, Hainsworth JD, Cohn AL, McIntyre HJ, Fernando IJ, Backstrom JT, Beach CL: Hematologic response to three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes. J Clin Oncol; 2009 Apr 10;27(11):1850-6
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  • PURPOSE: Azacitidine (AZA) is effective treatment for myelodysplastic syndromes (MDS) at a dosing schedule of 75 mg/m(2)/d subcutaneously for 7 days every 4 weeks.
  • PATIENTS AND METHODS: MDS patients were randomly assigned to one of three regimens every 4 weeks for six cycles: AZA 5-2-2 (75 mg/m(2)/d subcutaneously for 5 days, followed by 2 days no treatment, then 75 mg/m(2)/d for 2 days); AZA 5-2-5 (50 mg/m(2)/d subcutaneously for 5 days, followed by 2 days no treatment, then 50 mg/m(2)/d for 5 days); or AZA 5 (75 mg/m(2)/d subcutaneously for 5 days).
  • RESULTS: Of patients randomly assigned to AZA 5-2-2 (n = 50), AZA 5-2-5 (n = 51), or AZA 5 (n = 50), most were French-American-British (FAB) lower risk (refractory anemia [RA]/RA with ringed sideroblasts/chronic myelomonocytic leukemia with < 5% bone marrow blasts, 63%) or RA with excess blasts (30%), and 79 (52%) completed > or = six treatment cycles.
  • [MeSH-major] Antimetabolites, Antineoplastic / administration & dosage. Azacitidine / administration & dosage. Myelodysplastic Syndromes / blood. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Blood Transfusion. Dose-Response Relationship, Drug. Female. Humans. Male. Middle Aged. Treatment Outcome

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  • (PMID = 19255328.001).
  • [ISSN] 1527-7755
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Multicenter Study; Randomized Controlled Trial
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; M801H13NRU / Azacitidine
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13. Kaur A, Yu SS, Lee AJ, Chiao TB: Thalidomide-induced sinus bradycardia. Ann Pharmacother; 2003 Jul-Aug;37(7-8):1040-3
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  • CASE SUMMARY: A 72-year-old white man, with transfusion-dependent refractory anemia with ringed sideroblasts and hypertension treated with atenolol, was started on thalidomide 100 mg at bedtime.
  • Concurrent medications affecting the heart rate may also increase the risk of thalidomide-induced bradycardia.
  • CONCLUSIONS: Despite the low incidence of thalidomide-induced bradycardia, it appears to be an important adverse effect, particularly in patients with comorbidities or concurrent medications that decrease heart rate.
  • [MeSH-minor] Aged. Anemia / chemically induced. Anemia / drug therapy. Blood Transfusion / adverse effects. Heart Rate / drug effects. Humans. Male

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  • (PMID = 12841816.001).
  • [ISSN] 1060-0280
  • [Journal-full-title] The Annals of pharmacotherapy
  • [ISO-abbreviation] Ann Pharmacother
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Immunosuppressive Agents; 4Z8R6ORS6L / Thalidomide
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14. 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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  • 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).
  • The mutation appeared at relapse after chemotherapy for RAEB-T.
  • [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

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  • (PMID = 12592334.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / CCAAT-Enhancer-Binding Protein-alpha; 0 / DNA Primers
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15. 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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16. 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.
  • 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

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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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17. Raza A, Candoni A, Khan U, Lisak L, Tahir S, Silvestri F, Billmeier J, Alvi MI, Mumtaz M, Gezer S, Venugopal P, Reddy P, Galili N: Remicade as TNF suppressor in patients with myelodysplastic syndromes. Leuk Lymphoma; 2004 Oct;45(10):2099-104
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  • Median age was 68 years, 33 had primary MDS, 14 had refractory anemia (RA), 14 RA with ringed sideroblasts, 9 RA with excess blasts.
  • Nine patients stopped therapy prior to completing 4 cycles, 3 from cohort 1 and 6 from cohort 2 and response was evaluated using the International Working Group criteria in 28 patients who completed the 4 cycles.
  • We conclude that Remicade may have a variety of activities in low risk MDS patients, is well tolerated with a high patient compliance, and may be considered for combination therapy in the future.
  • [MeSH-major] Antibodies, Monoclonal / administration & dosage. Myelodysplastic Syndromes / drug therapy. Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • [MeSH-minor] Aged. Anemia, Refractory. Chromosome Aberrations. Cytogenetic Analysis. Disease Progression. Female. Humans. Infliximab. Male. Pancytopenia / drug therapy. Patient Compliance. Pilot Projects. Remission Induction. Treatment Outcome

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  • (PMID = 15370256.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / P01CA 75606
  • [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 / Antibodies, Monoclonal; 0 / Tumor Necrosis Factor-alpha; B72HH48FLU / Infliximab
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18. Baumann I, Scheid C, Koref MS, Swindell R, Stern P, Testa NG: Autologous lymphocytes inhibit hemopoiesis in long-term culture in patients with myelodysplastic syndrome. Exp Hematol; 2002 Dec;30(12):1405-11
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  • OBJECTIVE: The current therapy of myelodysplastic syndrome (MDS) is unsatisfactory and comprises mainly supportive treatment or antileukemic chemotherapy.
  • Recent studies about successful immunosuppressive therapy suggest an autoimmune mechanism in subtypes of myelodysplastic syndrome.
  • PATIENTS AND METHODS: To investigate this hypothesis, bone marrow mononuclear cells (MNC) from 15 patients with low-grade MDS, refractory anemia, and refractory anemia with ringed sideroblasts (RA and RARS), and from 7 normal donors were depleted of CD2(+), CD5(+), and CD7(+) lymphocytes using magnetic cell sorting.
  • CONCLUSION: These results provide a rationale for the recently described successful treatment of MDS with immunosuppressive therapy.
  • [MeSH-minor] Adolescent. Adult. Aged. Aged, 80 and over. Anemia, Refractory / etiology. Anemia, Refractory / immunology. Anemia, Refractory / pathology. Bone Marrow / pathology. Case-Control Studies. Child. Clone Cells / pathology. Coculture Techniques. Hematopoietic Stem Cells / cytology. Humans. Immunophenotyping. Leukocytes, Mononuclear / pathology. Loss of Heterozygosity. Lymphocyte Depletion. Middle Aged. Stromal Cells / cytology


19. Schmidt-Mende J, Tehranchi R, Forsblom AM, Joseph B, Christensson B, Fadeel B, Zhivotovsky B, Hellström-Lindberg E: Granulocyte colony-stimulating factor inhibits Fas-triggered apoptosis in bone marrow cells isolated from patients with refractory anemia with ringed sideroblasts. Leukemia; 2001 May;15(5):742-51
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  • [Title] Granulocyte colony-stimulating factor inhibits Fas-triggered apoptosis in bone marrow cells isolated from patients with refractory anemia with ringed sideroblasts.
  • Treatment with granulocyte colony-stimulating factor (G-CSF) plus erythropoietin may synergistically improve hemoglobin levels and reduce bone marrow apoptosis in patients with refractory anemia with ringed sideroblasts (RARS).
  • [MeSH-major] Anemia, Sideroblastic / drug therapy. Antigens, CD95 / physiology. Apoptosis / drug effects. Bone Marrow Cells / drug effects. Granulocyte Colony-Stimulating Factor / pharmacology
  • [MeSH-minor] Aged. Aged, 80 and over. Amino Acid Chloromethyl Ketones / therapeutic use. Caspase 3. Caspase 8. Caspase 9. Caspases / drug effects. Caspases / metabolism. DNA Fragmentation / drug effects. Erythroid Precursor Cells / drug effects. Erythroid Precursor Cells / physiology. Humans. Middle Aged. Mitochondria / drug effects. Mitochondria / pathology

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  • (PMID = 11368434.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Amino Acid Chloromethyl Ketones; 0 / Antigens, CD95; 0 / benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 143011-72-7 / Granulocyte Colony-Stimulating Factor; EC 3.4.22.- / CASP3 protein, human; EC 3.4.22.- / CASP8 protein, human; EC 3.4.22.- / CASP9 protein, human; EC 3.4.22.- / Caspase 3; EC 3.4.22.- / Caspase 8; EC 3.4.22.- / Caspase 9; EC 3.4.22.- / Caspases
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20. Oertel J, Oertel B, Dörken B: Detection of small numbers of cells characteristic for haematological disorders in peripheral blood (the deep diff). Clin Lab Haematol; 2002 Apr;24(2):73-80
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  • [Title] Detection of small numbers of cells characteristic for haematological disorders in peripheral blood (the deep diff).
  • This approach (the 'deep diff') enabled the detection of small numbers of diagnostically significant cells in a majority of patients.
  • We found ringed sideroblasts in 5/7 patients with sideroblastic anaemia and megaloblasts in 9/10 patients with megaloblastic anaemia.
  • Increased blasts were also observed in six patients with refractory anaemia with excess of blasts (RAEB).
  • Decreased blasts were found in five patients with aplastic anaemia and in nine patients with bone marrow aplasia after intensive chemotherapy.
  • [MeSH-minor] Anemia / blood. Anemia, Refractory, with Excess of Blasts / blood. Centrifugation. Coloring Agents. Eosine Yellowish-(YS). Humans. Leukemia / blood. Lymphoma, Non-Hodgkin / blood. Methylene Blue. Neoplastic Cells, Circulating. Retrospective Studies. Staining and Labeling / methods. Waldenstrom Macroglobulinemia / blood

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  • (PMID = 11985551.001).
  • [ISSN] 0141-9854
  • [Journal-full-title] Clinical and laboratory haematology
  • [ISO-abbreviation] Clin Lab Haematol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Coloring Agents; 0 / May-Grunwald Giemsa; T42P99266K / Methylene Blue; TDQ283MPCW / Eosine Yellowish-(YS)
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21. Shin SJ, Chun SH, Kim KO, Kim MK, Lee KH, Hyun MS, Cho HS: Myelodysplastic syndrome with complex karyotypic abnormality in a patient with Waldenström's macroglobulinemia after sequential treatment with chlorambucil and fludarabine. Jpn J Clin Oncol; 2005 Oct;35(10):622-5
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  • [Title] Myelodysplastic syndrome with complex karyotypic abnormality in a patient with Waldenström's macroglobulinemia after sequential treatment with chlorambucil and fludarabine.
  • A therapy-related myelodysplastic syndrome (t-MDS) during the course of Waldenström's macroglobulinemia (WM) has been observed in rare patients.
  • In most of them, the condition developed after treatment with alkylating agents.
  • He was treated with intermittent oral chlorambucil for 12 months and three cycles of fludarabine, and complete response was achieved after fludarabine treatment.
  • During routine outpatient follow-up, severe anemia occurred.
  • His bone marrow aspirate showed dysplastic hemopoiesis with ringed sideroblasts and siderocytes, which is consistent with MDS (refractory anemia with ringed sideroblasts).
  • When decision is made to treat WM with chlorambucil and/or fludarabine, a potential risk for t-MDS or therapy-related acute myeloid leukemia should be considered and a close hematologic monitoring is needed.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / adverse effects. Chromosome Aberrations. Myelodysplastic Syndromes / chemically induced. Myelodysplastic Syndromes / genetics. Waldenstrom Macroglobulinemia / drug therapy
  • [MeSH-minor] Aged. Antineoplastic Agents, Alkylating / administration & dosage. Antineoplastic Agents, Alkylating / adverse effects. Bone Marrow / pathology. Chlorambucil / administration & dosage. Chlorambucil / adverse effects. Chromosome Deletion. Chromosomes, Human, Pair 12. Chromosomes, Human, Pair 18. Chromosomes, Human, Pair 5. Drug Administration Schedule. Humans. Male. Monosomy. Vidarabine / administration & dosage. Vidarabine / adverse effects. Vidarabine / analogs & derivatives

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  • (PMID = 16172172.001).
  • [ISSN] 0368-2811
  • [Journal-full-title] Japanese journal of clinical oncology
  • [ISO-abbreviation] Jpn. J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 18D0SL7309 / Chlorambucil; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine
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22. Voulgari PV, Hatzimichael EC, Tsiara S, Tzallas C, Drosos AA, Bourantas KL: Investigation for the presence of anti-erythropoietin antibodies in patients with myelodysplastic syndromes. Eur J Haematol; 2001 Jan;66(1):31-6
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  • OBJECTIVES: Recombinant human erythropoietin (rHuEpo) improves anemia in 25% of patients with myelodysplastic syndromes (MDS).
  • The variable and sometimes low response rate to rHuEpo treatment raises the question whether the existence of autoantibodies against erythropoietin (epo) is partially responsible.
  • Sixteen patients had refractory anemia (RA), 13 had RA with ringed sideroblasts, 3 had RA with excess of blasts (RAEB), 9 had RAEB in transformation and 2 patients had chronic myelomonocytic leukemia.
  • They were divided in 3 groups according to rHuEpo treatment.
  • Group A consisted of 10 patients who did not receive rHuEpo treatment.
  • Group B included 13 patients who were on rHuEpo treatment (150 IU/kg subcutaneously, 3 times weekly) showing an increase of hemoglobin (Hb) values or reduction of transfusion requirements and Group C consisted of 20 patients who did not respond or stopped responding to rHuEpo treatment.
  • CONCLUSION: We suggest that anti-epo autoantibodies do not contribute to the development of MDS-related anemia and are not responsible for the modest response to rHuEpo treatment.
  • Further investigation is needed to identify possible reasons for the low response rate to rHuEpo treatment.
  • [MeSH-minor] Aged. Aged, 80 and over. Anemia, Refractory / blood. Anemia, Refractory / drug therapy. Anemia, Refractory / immunology. Anemia, Refractory / therapy. Anemia, Refractory, with Excess of Blasts / blood. Anemia, Refractory, with Excess of Blasts / drug therapy. Anemia, Refractory, with Excess of Blasts / immunology. Anemia, Refractory, with Excess of Blasts / therapy. Antibody Specificity. Blood Cell Count. Blood Transfusion. Combined Modality Therapy. Female. Hemoglobins / analysis. Humans. Leukemia, Myelomonocytic, Chronic / blood. Leukemia, Myelomonocytic, Chronic / drug therapy. Leukemia, Myelomonocytic, Chronic / immunology. Leukemia, Myelomonocytic, Chronic / therapy. Male. Middle Aged. Recombinant Proteins / immunology. Recombinant Proteins / therapeutic use. Treatment Failure

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  • [CommentIn] Eur J Haematol. 2002 Sep;69(3):189-90 [12406016.001]
  • (PMID = 11168505.001).
  • [ISSN] 0902-4441
  • [Journal-full-title] European journal of haematology
  • [ISO-abbreviation] Eur. J. Haematol.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] Denmark
  • [Chemical-registry-number] 0 / Autoantibodies; 0 / Autoantigens; 0 / Hemoglobins; 0 / Isoantibodies; 0 / Isoantigens; 0 / Recombinant Proteins; 11096-26-7 / Erythropoietin
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23. Sadek I, Zayed E, Hayne O, Fernandez L: Prolonged complete remission of myelodysplastic syndrome treated with danazol, retinoic acid and low-dose prednisone. Am J Hematol; 2000 Aug;64(4):306-10
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  • Different medications have been tried in MDS; however, no effective treatment has been yet established.
  • We report a patient with MDS who achieved a complete remission in response to combination therapy of danazol, retinoic acid, and prednisone.
  • A 53-year-old female presented with pancytopenia, macrocytosis, and hypercellular bone marrow with erythroid hyperplasia and dysplasia and 10% ringed sideroblasts.
  • She was diagnosed as having MDS-refractory anemia and was given blood transfusions to maintain blood cell counts at acceptable levels.
  • At the same time, she was started on a combination of danazol (600 mg/day), retinoic acid (100 mg/day), and prednisone (10 mg every other day).
  • She was continued on the same combination treatment for 86 months, and she remained in complete clinical remission.
  • This is the first reported case of MDS-RA that sustained a complete hematologic remission for a prolonged period in response to this combination treatment.
  • This report indicates that restoration of normal hematopoiesis, prolongation of disease-free survival, and delay in the transformation to acute leukemia may be achieved by this combination of treatment in a subset of patients with MDS, especially refractory anemia with severe thrombocytopenia.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Danazol / administration & dosage. Estrogen Antagonists / administration & dosage. Myelodysplastic Syndromes / drug therapy. Prednisone / administration & dosage. Tretinoin / administration & dosage
  • [MeSH-minor] Drug Therapy, Combination. Female. Humans. Middle Aged. Remission Induction

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  • [Copyright] Copyright 2000 Wiley-Liss, Inc.
  • (PMID = 10911385.001).
  • [ISSN] 0361-8609
  • [Journal-full-title] American journal of hematology
  • [ISO-abbreviation] Am. J. Hematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Estrogen Antagonists; 5688UTC01R / Tretinoin; N29QWW3BUO / Danazol; VB0R961HZT / Prednisone
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24. Heller T, Höchstetter V, Basler M, Borck V: [Vitamin B6-sensitive hereditary sideroblastic anemia]. Dtsch Med Wochenschr; 2004 Jan 23;129(4):141-4
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  • [Title] [Vitamin B6-sensitive hereditary sideroblastic anemia].
  • HISTORY: A 30-year-old patient was admitted for investigation of microcytotic, hypochromic anemia (hemoglobin 8.3 g/dl) with splenomegaly.
  • Prussian-blue staining revealed an increased number of ring sideroblasts, thus myelodysplastic syndrome (refractory anemia with ringsideroblasts) was suspected.
  • DIAGNOSIS AND TREATMENT: Review of former laboratory values and investigations of the patient's family revealed the correct diagnosis of x-linked sideroblastic anemia (XLSA).
  • Hemoglobin levels steadily increased, so the diagnosis of pyridoxine-responsive sideroblastic anemia was made.
  • Therapy with deferoxamine and phlebotomies was initiated.
  • A correct diagnosis is especially important because of the uncomplicated therapeutic options.
  • [MeSH-major] Anemia, Sideroblastic / drug therapy. Genetic Diseases, X-Linked / drug therapy. Vitamin B 6 / therapeutic use
  • [MeSH-minor] Administration, Oral. Adult. Bone Marrow / pathology. Deferoxamine / therapeutic use. Diagnosis, Differential. Ferritins / blood. Hematologic Tests. Hemoglobins / analysis. Humans. Iron Chelating Agents / therapeutic use. Liver / pathology. Male. Pedigree

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  • (PMID = 14724775.001).
  • [ISSN] 0012-0472
  • [Journal-full-title] Deutsche medizinische Wochenschrift (1946)
  • [ISO-abbreviation] Dtsch. Med. Wochenschr.
  • [Language] ger
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Hemoglobins; 0 / Iron Chelating Agents; 8059-24-3 / Vitamin B 6; 9007-73-2 / Ferritins; J06Y7MXW4D / Deferoxamine
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25. Besa EC, Kim PW, Haurani FI: Treatment of primary defective iron-reutilization syndrome: revisited. Ann Hematol; 2000 Aug;79(8):465-8
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  • [Title] Treatment of primary defective iron-reutilization syndrome: revisited.
  • We encountered two patients who presented with hypochromic-microcytic anemia and were refractory to iron therapy.
  • The symptoms were suggestive of anemia of chronic disease (ACD); however, there was no evidence of any such disease, either inflammatory or malignant.
  • The hematologic picture consisted of hypochromic-microcytic anemia, low serum iron, low to normal iron binding capacity, high serum ferritin, and increased bone marrow iron in the absence of ringed sideroblasts.
  • These patients had symptomatic anemia and received danazol (200 mg orally) three times per day to which they responded very well with an increase of approximately 3 g in the hemoglobin concentration over 1 year and amelioration of their symptoms.
  • In the differential diagnosis of hypochromic-microcytic anemia, especially in postmenopausal women, one has to consider this type of treatable anemia when more common types such as iron deficiency, chronic inflammation, malignancy, sideroblastic anemia, or thalassemia have been ruled out.
  • [MeSH-major] Anemia, Iron-Deficiency / drug therapy
  • [MeSH-minor] Aged. Cohort Studies. Danazol / therapeutic use. Estrogen Antagonists / therapeutic use. Female. Humans. Iron / metabolism. Middle Aged

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  • (PMID = 10985370.001).
  • [ISSN] 0939-5555
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] GERMANY
  • [Chemical-registry-number] 0 / Estrogen Antagonists; E1UOL152H7 / Iron; N29QWW3BUO / Danazol
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26. Tehranchi R: Impact of growth factors in the regulation of apoptosis in low-risk myelodysplastic syndromes. Med Oncol; 2006;23(1):37-49
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  • Erythroid apoptosis is thought to be the main mechanism underlying the severe anemia observed in the low-risk subgroups, refractory anemia (RA) and RA with ringed sideroblasts (RARS).
  • Treatment with erythropoietin (Epo) alone or in combination with granulocyte colony-stimulating factor (G-CSF) may significantly improve anemia and reduce bone marrow apoptosis.
  • [MeSH-major] Apoptosis / drug effects. Erythropoietin / pharmacology. Granulocyte Colony-Stimulating Factor / pharmacology. Myelodysplastic Syndromes / drug therapy

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  • (PMID = 16645228.001).
  • [ISSN] 1357-0560
  • [Journal-full-title] Medical oncology (Northwood, London, England)
  • [ISO-abbreviation] Med. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / DNA, Mitochondrial; 11096-26-7 / Erythropoietin; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 9007-73-2 / Ferritins
  • [Number-of-references] 136
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27. Howe RB, Porwit-MacDonald A, Wanat R, Tehranchi R, Hellström-Lindberg E: The WHO classification of MDS does make a difference. Blood; 2004 May 1;103(9):3265-70
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  • The WHO classification reliably predicted therapeutic response to the combination of granulocyte colony-stimulating factor (G-CSF) and erythropoietin (Epo).
  • The response rate differed significantly between refractory anemia with ringed sideroblasts (RARS) and refractory anemia with multilineage dysplasia and ringed sideroblasts (RCMD/RS) with regard to therapeutic response (75% versus 9%; P =.003).
  • [MeSH-minor] Classification / methods. Drug Therapy, Combination. Erythropoietin / therapeutic use. Follow-Up Studies. Granulocyte Colony-Stimulating Factor / therapeutic use. Humans. Observer Variation. Predictive Value of Tests. Prognosis. Retrospective Studies. Survival Rate. Treatment Outcome

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  • (PMID = 14684416.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 11096-26-7 / Erythropoietin; 143011-72-7 / Granulocyte Colony-Stimulating Factor
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28. 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%.
  • 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

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  • (PMID = 20873246.001).
  • [ISSN] 0040-3660
  • [Journal-full-title] Terapevticheskiĭ arkhiv
  • [ISO-abbreviation] Ter. Arkh.
  • [Language] rus
  • [Publication-type] Clinical Trial; English Abstract; Journal Article
  • [Publication-country] Russia (Federation)
  • [Chemical-registry-number] 0 / Immunosuppressive Agents; 83HN0GTJ6D / Cyclosporine
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29. 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


30. Gotlib J, Lavori P, Quesada S, Stein RS, Shahnia S, Greenberg PL: A Phase II intra-patient dose-escalation trial of weight-based darbepoetin alfa with or without granulocyte-colony stimulating factor in myelodysplastic syndromes. Am J Hematol; 2009 Jan;84(1):15-20
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  • Patients with refractory anemia with ringed sideroblasts (RARS) commenced DA at 9 mcg/kg/week.
  • A minority of subjects (12%) developed low-level non-neutralizing anti-DA antibodies.
  • [MeSH-major] Erythropoietin / analogs & derivatives. Granulocyte Colony-Stimulating Factor / therapeutic use. Hematinics / therapeutic use. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Darbepoetin alfa. Drug Therapy, Combination. Female. Humans. Male. Middle Aged

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  • [CommentIn] Am J Hematol. 2009 Jan;84(1):3-5 [19037863.001]
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  • (PMID = 19006226.001).
  • [ISSN] 1096-8652
  • [Journal-full-title] American journal of hematology
  • [ISO-abbreviation] Am. J. Hematol.
  • [Language] eng
  • [Grant] United States / NHLBI NIH HHS / HL / K23 HL004409; United States / NCI NIH HHS / CA / P30 CA124435; United States / NHLBI NIH HHS / HL / K23 HL04409
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Hematinics; 11096-26-7 / Erythropoietin; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 15UQ94PT4P / Darbepoetin alfa
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31. 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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32. Raza A, Mehdi M, Mumtaz M, Ali F, Lascher S, Galili N: Combination of 5-azacytidine and thalidomide for the treatment of myelodysplastic syndromes and acute myeloid leukemia. Cancer; 2008 Oct 1;113(7):1596-604
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  • [Title] Combination of 5-azacytidine and thalidomide for the treatment of myelodysplastic syndromes and acute myeloid leukemia.
  • BACKGROUND: The treatment of myelodysplastic syndromes (MDS) remains a challenge to the clinician despite recent advances.
  • Many patients will either not respond or will have only limited and/or brief responses to single-agent therapy.
  • Six patients had refractory anemia (RA), 2 patients had RA with ringed sideroblasts, 10 patients had RA with excess blasts (RAEB), 1 patient had RAEB in transformation, 4 patients had chronic myelomonocytic leukemia, 1 patient had chronic idiopathic myelofibrosis, and 16 patients had AML.
  • It was noteworthy that 9 of 14 patients with AML had a history of prior MDS, 2 of 9 patients achieved a CR, 4 of 9 patients had HI (HI-E and bilineage HI), and 1 patient had stable disease and was continuing treatment.
  • CONCLUSIONS: The current findings indicated that a combination of low-dose AZA and thalidomide was well tolerated and was effective therapy for the treatment of patients with MDS and AML arising from prior MDS.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Azacitidine / administration & dosage. Leukemia, Myeloid, Acute / drug therapy. Myelodysplastic Syndromes / drug therapy. Thalidomide / administration & dosage
  • [MeSH-minor] Bone Marrow Cells / pathology. Drug Administration Schedule. Humans. Oligonucleotide Array Sequence Analysis. Pilot Projects. Survival Analysis. Treatment Outcome


33. 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)].
  • 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


34. Grinblatt DL, Yu D, Hars V, Vardiman JW, Powell BL, Nattam S, Silverman LR, de Castro C 3rd, Stone RM, Bloomfield CD, Larson RA, Cancer and Leukemia Group: Treatment of myelodysplastic syndrome with 2 schedules and doses of oral topotecan: a randomized phase 2 trial by the Cancer and Leukemia Group B (CALGB 19803). Cancer; 2009 Jan 1;115(1):84-93
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  • [Title] Treatment of myelodysplastic syndrome with 2 schedules and doses of oral topotecan: a randomized phase 2 trial by the Cancer and Leukemia Group B (CALGB 19803).
  • METHODS: Patients with previously untreated primary or therapy-related MDS were eligible.
  • Patients with refractory anemia (RA), RA with ringed sideroblasts, or refractory cytopenia with multilineage dysplasia (RCMD) were eligible only if they were dependent on erythrocyte transfusion, had a platelet count<50,000/microL, or had an absolute neutrophil count<1000/microL with a recent infection that required antibiotics.
  • Responding patients continued until they developed disease progression or unacceptable toxicity or until they had received 2 cycles beyond a complete response.
  • RESULTS: Ninety patients received treatment, including 46 patients on Arm A and 44 patients on Arm B.
  • There were 8 treatment-related deaths from infection (6 deaths) and bleeding (2 deaths).
  • CONCLUSIONS: Oral topotecan in the dose and schedules evaluated in this trial demonstrated only a modest response rate with a troublesome toxicity profile in the treatment of MDS.

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  • [Copyright] Copyright (c) 2008 American Cancer Society.
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  • (PMID = 19025972.001).
  • [ISSN] 0008-543X
  • [Journal-full-title] Cancer
  • [ISO-abbreviation] Cancer
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / U10 CA047577; United States / NCI NIH HHS / CA / U10 CA032291; United States / NCI NIH HHS / CA / CA33601; United States / NCI NIH HHS / CA / CA04457; United States / NCI NIH HHS / CA / CA11789; United States / NCI NIH HHS / CA / U10 CA077658; United States / NCI NIH HHS / CA / CA02599; United States / NCI NIH HHS / CA / CA47577; United States / NCI NIH HHS / CA / CA47555; United States / NCI NIH HHS / CA / CA35113; United States / NCI NIH HHS / CA / CA32291; United States / NCI NIH HHS / CA / CA29165; United States / NCI NIH HHS / CA / CA41287; United States / NCI NIH HHS / CA / CA03927; United States / NCI NIH HHS / CA / U10 CA031946; United States / NCI NIH HHS / CA / U10 CA033601; United States / NCI NIH HHS / CA / U10 CA031946-25; United States / NCI NIH HHS / CA / CA35199; United States / NCI NIH HHS / CA / CA12046; United States / NCI NIH HHS / CA / CA16450; United States / NCI NIH HHS / CA / CA031946-25; United States / NCI NIH HHS / CA / U10 CA004326; United States / NCI NIH HHS / CA / U10 CA041287; United States / NCI NIH HHS / CA / U10 CA035113; United States / NCI NIH HHS / CA / U10 CA047559; United States / NCI NIH HHS / CA / CA04326; United States / NCI NIH HHS / CA / CA74811; United States / NCI NIH HHS / CA / CA21060; United States / NCI NIH HHS / CA / CA47559; United States / NCI NIH HHS / CA / CA47642; United States / NCI NIH HHS / CA / U10 CA074811; United States / NCI NIH HHS / CA / CA77658; United States / NCI NIH HHS / CA / CA12449; United States / NCI NIH HHS / CA / U10 CA047642; United States / NCI NIH HHS / CA / CA31983; United States / NCI NIH HHS / CA / CA31946; United States / NCI NIH HHS / CA / U10 CA003927; United States / NCI NIH HHS / CA / CA07968
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 7M7YKX2N15 / Topotecan
  • [Other-IDs] NLM/ NIHMS89209; NLM/ PMC2887616
  • [Investigator] Winer EP; Ernstoff MS; Crawford J; Giguere JK; Kugler JW; Grossbard ML; Graziano SL; Bloomfield CD; Mortimer J; Fleming G; Feldman LE; Clamon G; Edelman M; Peterson BA; Perry MC; Shea TC; Niell HB; Hurd DD; Wadler S
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35. Yazji S, Giles FJ, Tsimberidou AM, Estey EH, Kantarjian HM, O'Brien SA, Kurzrock R: Antithymocyte globulin (ATG)-based therapy in patients with myelodysplastic syndromes. Leukemia; 2003 Nov;17(11):2101-6
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  • [Title] Antithymocyte globulin (ATG)-based therapy in patients with myelodysplastic syndromes.
  • The purpose of this study was to determine the efficacy of and tolerance to antithymocyte globulin (ATG)-based therapy in patients with myelodysplastic syndrome (MDS).
  • Therapy consisted of ATG 40 mg/kg/day daily intravenously (i.v.) for 4 days; cyclosporine daily orally for 6 months with levels titrated between 200 and 400 mg/dl; and methylprednisone 1 mg/kg i.v. daily before each dose of ATG.
  • A total of 18 patients had refractory anemia (RA) or RA with ringed sideroblasts (RARS), 10 patients had RA with excess blasts (RAEB), two patients had RAEB in transformation, and one patient had chronic myelomonocytic leukemia.
  • [MeSH-major] Antilymphocyte Serum / therapeutic use. Immunosuppressive Agents / therapeutic use. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Adult. Aged. Blood Transfusion. Cyclosporine / therapeutic use. Female. Hematocrit. Humans. Karyotyping. Male. Methylprednisolone / therapeutic use. Middle Aged. Platelet Count. Treatment Outcome


36. Kaminskas E, Farrell A, Abraham S, Baird A, Hsieh LS, Lee SL, Leighton JK, Patel H, Rahman A, Sridhara R, Wang YC, Pazdur R, FDA: Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes. Clin Cancer Res; 2005 May 15;11(10):3604-8
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  • [Title] Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes.
  • Food and Drug Administration for marketing approval of azacitidine as injectable suspension (Vidaza, Pharmion Corporation, Boulder, CO) for treatment of patients with myelodysplastic syndrome.
  • EXPERIMENTAL DESIGN: In one phase 3 controlled trial, 191 study subjects were randomized to treatment with azacitidine or to observation; an additional 120 patients were treated with azacitidine in two phase 2 single arm studies.
  • RESULTS: In the controlled trial, the overall response rate was 15.7% in the azacitidine treatment group; there were no responders in the observation group (P < 0.0001).
  • Food and Drug Administration approved azacitidine as injectable suspension for treatment of patients with the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia.
  • Azacitidine is the first agent approved for treatment of myelodysplastic syndrome.
  • [MeSH-major] Antimetabolites, Antineoplastic / therapeutic use. Azacitidine / therapeutic use. Drug Approval. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Humans. Injections, Subcutaneous. Treatment Outcome. United States. United States Food and Drug Administration

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  • (PMID = 15897554.001).
  • [ISSN] 1078-0432
  • [Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research
  • [ISO-abbreviation] Clin. Cancer Res.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antimetabolites, Antineoplastic; M801H13NRU / Azacitidine
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37. Chuncharunee S, Intragumtornchai T, Chaimongkol B, Prayoonwiwat W, Leelasiri A, Lekhakula A, Chansung K, Yoshida Y: Treatment of myelodysplastic syndrome with low-dose human granulocyte colony-stimulating factor: a multicenter study. Int J Hematol; 2001 Aug;74(2):144-6
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  • [Title] Treatment of myelodysplastic syndrome with low-dose human granulocyte colony-stimulating factor: a multicenter study.
  • Eligibility criteria were the following: French-American-British disease classification subtype refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), or refractory anemia with excess blasts (RAEB) with an absolute neutrophil count (ANC) of <1.5 x 10(9)/L.
  • Criteria indicating response to treatment were ANC of >1.5 x 10(9)/L and doubling of ANC on at least 2 occasions.
  • [MeSH-major] Granulocyte Colony-Stimulating Factor / administration & dosage. Myelodysplastic Syndromes / drug therapy. Recombinant Proteins / administration & dosage
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Dose-Response Relationship, Drug. Female. Hematopoiesis / drug effects. Humans. Male. Middle Aged. Neutropenia / etiology

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  • (PMID = 11594513.001).
  • [ISSN] 0925-5710
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Multicenter Study
  • [Publication-country] Ireland
  • [Chemical-registry-number] 0 / Recombinant Proteins; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 6WS4C399GB / lenograstim
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38. 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


39. 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.
  • 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.


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


41. Ljung T, Bäck R, Hellström-Lindberg E: Hypochromic red blood cells in low-risk myelodysplastic syndromes: effects of treatment with hemopoietic growth factors. Haematologica; 2004 Dec;89(12):1446-53
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  • [Title] Hypochromic red blood cells in low-risk myelodysplastic syndromes: effects of treatment with hemopoietic growth factors.
  • BACKGROUND AND OBJECTIVES: The anemia of low-risk myelodysplastic syndromes (MDS), refractory anemia (RA) and RA with ringed sideroblasts (RARS), may respond to treatment with hematopoietic growth factors (GF)); erythropoietin (Epo) +/- granulocyte colony-stimulating factor (G-CSF).
  • The present study was designed to assess whether functional iron deficiency may develop in MDS patients receiving these treatments.
  • These values increased further after GF-treatment (median 11%, 57%, and 105 fL, respectively), in spite of improved hemoglobin values and adequate body iron stores.
  • The values observed in untreated RA patients largely fell within the normal range, and there was no significant influence of GF treatment.
  • Notably, the hemoglobin content of reticulocytes (MCHr) did not differ between MDS and controls, and was not influenced by GF treatment.
  • The proportion of abnormal cells increases after successful pro-erythroid GF treatment, indicating that GF promote erythroblast survival, and maturation into erythrocytes.
  • [MeSH-major] Anemia, Refractory / drug therapy. Anemia, Sideroblastic / drug therapy. Erythropoietin / therapeutic use. Granulocyte Colony-Stimulating Factor / therapeutic use. Iron / blood
  • [MeSH-minor] Blood Cell Count. Drug Therapy, Combination. Erythrocyte Indices. Erythrocyte Transfusion. Erythrocytes / chemistry. Ferritins / blood. Hemoglobins / analysis. Humans. Methylmalonic Acid / blood. Reticulocytes / chemistry. Reticulocytes / ultrastructure. Risk. Transferrin / analysis

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  • (PMID = 15590394.001).
  • [ISSN] 1592-8721
  • [Journal-full-title] Haematologica
  • [ISO-abbreviation] Haematologica
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Hemoglobins; 0 / Transferrin; 11096-26-7 / Erythropoietin; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 8LL8S712J7 / Methylmalonic Acid; 9007-73-2 / Ferritins; E1UOL152H7 / Iron
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42. Ishikawa T, Tohyama K, Nakao S, Yoshida Y, Teramura M, Motoji T, Takatoku M, Kurokawa M, Mitani K, Uchiyama T, Omine M: A prospective study of cyclosporine A treatment of patients with low-risk myelodysplastic syndrome: presence of CD55(-)CD59(-) blood cells predicts platelet response. Int J Hematol; 2007 Aug;86(2):150-7
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] A prospective study of cyclosporine A treatment of patients with low-risk myelodysplastic syndrome: presence of CD55(-)CD59(-) blood cells predicts platelet response.
  • Although immunosuppressive therapy using antithymocyte globulin or cyclosporine A (CSA) is effective in selected patients with low-risk myelodysplastic syndrome, the response rates reported so far are inconsistent, and the indication of immunosuppressive therapy for myelodysplastic syndrome has not been clearly defined.
  • We treated 20 myelodysplastic syndrome patients (17 refractory anemia cases [RA], 2 RA with excess blasts, and one RA with ringed sideroblasts) with 4 mg/kg per day of CSA for 24 weeks.
  • Most toxicities associated with CSA usage were manageable, and no patient had developed acute leukemia up to this point.
  • Short duration of illness, refractory anemia with minimal dysplasia determined by bone marrow morphology, and the presence of paroxysmal nocturnal hemoglobinuria-type cells were significantly associated with the platelet response.
  • In conclusion, CSA may be a therapeutic option for patients with RA who do not have adverse prognostic factors.
  • [MeSH-major] Blood Platelets / drug effects. Cyclosporine / administration & dosage. Myelodysplastic Syndromes / drug therapy. Predictive Value of Tests
  • [MeSH-minor] Adolescent. Adult. Aged. Antigens, CD55 / analysis. Antigens, CD59 / analysis. Erythrocyte Count. Female. Humans. Immunosuppressive Agents / therapeutic use. Male. Middle Aged. Neutrophils / cytology. Platelet Count. Prognosis. Prospective Studies. Risk Assessment. Treatment Outcome

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  • (PMID = 17875530.001).
  • [ISSN] 0925-5710
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antigens, CD55; 0 / Antigens, CD59; 0 / Immunosuppressive Agents; 83HN0GTJ6D / Cyclosporine
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43. Balleari E, Rossi E, Clavio M, Congiu A, Gobbi M, Grosso M, Secondo V, Spriano M, Timitilli S, Ghio R: Erythropoietin plus granulocyte colony-stimulating factor is better than erythropoietin alone to treat anemia in low-risk myelodysplastic syndromes: results from a randomized single-centre study. Ann Hematol; 2006 Mar;85(3):174-80
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Erythropoietin plus granulocyte colony-stimulating factor is better than erythropoietin alone to treat anemia in low-risk myelodysplastic syndromes: results from a randomized single-centre study.
  • Haemopoietic growth factors (HGF), i.e. erythropoietin [recombinant human erythropoietin (rHEPO)] or granulocyte colony stimulating factor (G-CSF), alone or in combination, have largely been used to treat anemia in myelodysplastic syndromes (MDS), but whether combined rHEPO and G-CSF is really superior to rHEPO alone is still under debate.
  • The aim of this study was to compare the effects of "standard" doses of rHEPO with the combination of rHEPO and G-CSF in the treatment of anemic patients with low-risk MDS in a prospective randomized trial.
  • Anemic patients with low-risk MDS were randomly assigned to receive either rHEPO (10,000 IU s.c. three times a week) or the same dosage of rHEPO+G-CSF (300 mug s.c. twice a week) for a minimum of 8 weeks.
  • Patients who were unresponsive to rHEPO were offered the combination therapy for another 8 weeks, whereas non-responders to rHEPO+G-CSF were considered "off study".
  • Responders continued the treatment indefinitely.
  • Both haematological response and changes in quality-of-life (QoL) scores (Functional Assessment of Cancer Therapy-Anemia) were recorded and evaluated.
  • Thirty consecutive patients [10 refractory anemia (RA), 5 RA with ringed sideroblasts, 7 refractory cytopenia with multilineage dysplasia, 5 RA with less than 10% blasts and 3 5q-syndrome] were enrolled in the study.
  • All of them (15 in the rHEPO arm and 15 in the rHEPO+G-CSF arm) were valuable after the first 8 weeks of treatment.
  • No relevant adverse effects were recorded for either treatment in any of the study patients.
  • Twenty responders continued the treatment.
  • Afterwards, 8/20 (40%) discontinued therapy because of the following: losing response (2), progression to high-risk MDS (3) and death due to other causes (3).
  • The remaining 12 are still responding and continuing treatment, with a median follow-up of 28 months.
  • Although our data were obtained from a relatively small cohort of patients, they indicate that the rHEPO+G-CSF treatment is more effective than rHEPO alone for correcting anemia in low-risk MDS patients and for making a relevant improvement in their QoL.
  • [MeSH-major] Anemia / drug therapy. Erythropoietin / administration & dosage. Granulocyte Colony-Stimulating Factor / administration & dosage. Myelodysplastic Syndromes / drug therapy
  • [MeSH-minor] Aged. Aged, 80 and over. Disease Progression. Disease-Free Survival. Erythropoiesis / drug effects. Female. Humans. Injections, Subcutaneous. Male. Middle Aged. Quality of Life. Recombinant Proteins. Remission Induction. Risk Factors






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