OverviewThe myelodysplastic syndromes (MDS) represent myeloid clonal hemopathies with relatively heterogeneous spectrums of presentation. The major clinical problems in these disorders are morbidities caused by cytopenias and the potential for MDS to evolve into acute myeloid leukemia (AML). In the general population, MDS occur in 5 per 100,000 people. However, among individuals older than 70 years, the incidence increases to between 22 and 45 per 100,000 and increases further with age.Managing MDS is complicated by the generally advanced age of the patients (median ages, 65–70 years), attendant nonhematologic comorbidities, and relative inability to tolerate certain intensive forms of therapy among older patients. In addition, when the illness progresses to AML, these patients experience lower response rates to standard therapy than those with de novo AML.1Diagnostic ClassificationInitial evaluation of patients with suspected MDS requires careful assessment of their peripheral blood smear and blood counts, marrow morphology, duration of their abnormal blood counts, other potential causes for their cytopenias, and concomitant illnesses. The French-American-British (FAB) classification initially categorized patients for the diagnostic evaluation of MDS.2 Dysplastic changes in at least 2 of the 3 hematopoietic cell lines have been used by most histopathologists to diagnose MDS. These changes include megaloblastoid erythropoiesis, nucleocytoplasmic asynchrony in the early myeloid and erythroid precursors, and dysmorphic megakaryocytes.3 Patients with MDS are classified as having 1 of 5 subtypes of disease: refractory anemia (RA); RA with ringed sideroblasts (RARS); RA with excess of blasts (RAEB); RAEB in transformation (RAEB-T); or chronic myelomonocytic leukemia...
  • 1.

    Greenberg P. The myelodysplastic syndromes. In: Hoffman R, Benz E, Shattil S., eds. Hematology: Basic Principles and Practice, 3rd ed. New York, NY: Churchill Livingstone; 2000:11061129.

    • Search Google Scholar
    • Export Citation
  • 2.

    Bennett JM, Catovsky D, Daniel MT. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982;51:189199.

  • 3.

    Kouides PA, Bennett JM. Morphology and classification of the myelodysplastic syndromes and their pathologic variants. Semin Hematol 1996;33:95110.

    • Search Google Scholar
    • Export Citation
  • 4.

    Brunning R, Bennett J, Flandrin G. Myelodysplastic syndromes. In: Jaffe E, Harris N, Stein H., eds. WHO Classification of Tumours. Pathology and Genetics of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001:6173.

    • Search Google Scholar
    • Export Citation
  • 5.

    Harris NL, Jaffe ES, Diebold J. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol 1999;17:38353849.

    • Search Google Scholar
    • Export Citation
  • 6.

    Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002;100:22922302.

  • 7.

    Kaloutsi V, Kohlmeyer U, Maschek H. Comparison of bone marrow and hematologic findings in patients with human immunodeficiency virus infection and those with myelodysplastic syndromes and infectious diseases. Am J Clin Pathol 1994;101:123129.

    • Search Google Scholar
    • Export Citation
  • 8.

    Swerdlow S, Campo E, Harris NL. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2008:88103.

    • Search Google Scholar
    • Export Citation
  • 9.

    Brunning R, Orazi A, Germing U. Myelodysplastic syndromes/neoplasms. In: Swerdlow SH, Campo E, Harris NL., eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th ed. Lyon, France: IARC Press; 2008:88103.

    • Search Google Scholar
    • Export Citation
  • 10.

    Vardiman JW, Thiele J, Arber DA. The 2008 revision of the WHO classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009;114:937951.

    • Search Google Scholar
    • Export Citation
  • 11.

    Greenberg P, Cox C, LeBeau MM. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997;89:20792088. Erratum in: Blood 1998;2091:1100.

    • Search Google Scholar
    • Export Citation
  • 12.

    List A, Dewald G, Bennett J. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 2006;355:14561465.

  • 13.

    Orazi A BJ, Germing U., eds. Myelodysplastic/myeloproliferative neoplasms. In: Swerdlow SH, Campo E, Harris NL., eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th ed. Lyon, France: IARC Press; 2008:7686.

    • Search Google Scholar
    • Export Citation
  • 14.

    Albitar M, Manshouri T, Shen Y. Myelodysplastic syndrome is not merely ``preleukemia''. Blood 2002;100:791798.

  • 15.

    Greenberg P, Anderson J, de Witte T. Problematic WHO reclassification of myelodysplastic syndromes. Members of the International MDS Study Group. J Clin Oncol 2000;18:34473452.

    • Search Google Scholar
    • Export Citation
  • 16.

    Germing U, Gattermann N, Strupp C. Validation of the WHO proposals for a new classification of primary myelodysplastic syndromes: a retrospective analysis of 1600 patients. Leuk Res 2000;24:983992.

    • Search Google Scholar
    • Export Citation
  • 17.

    Nosslinger T, Reisner R, Koller E. Myelodysplastic syndromes, from French-American-British to World Health Organization: comparison of classifications on 431 unselected patients from a single institution. Blood 2001;98:29352941.

    • Search Google Scholar
    • Export Citation
  • 18.

    Arber D, Porwit A, Brunning RD. Acute myeloid leukaemia with myelodysplasia-related changes. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. Acute Myeloid Leukemia and Related Precursor Neoplasms. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues, 4th ed. Lyon, France: IARC Press; 2008:124126.

    • Search Google Scholar
    • Export Citation
  • 19.

    Valent P, Horny HP, Bennett JM. Definitions and standards in the diagnosis and treatment of the myelodysplastic syndromes: consensus statements and report from a working conference. Leuk Res 2007;31:727736.

    • Search Google Scholar
    • Export Citation
  • 20.

    Dunn DE, Tanawattanacharoen P, Boccuni P. Paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure syndromes. Ann Intern Med 1999;131:401408.

    • Search Google Scholar
    • Export Citation
  • 21.

    Saunthararajah Y, Nakamura R, Nam JM. HLA-DR15 (DR2) is overrepresented in myelodysplastic syndrome and aplastic anemia and predicts a response to immunosuppression in myelodysplastic syndrome. Blood 2002;100:15701574.

    • Search Google Scholar
    • Export Citation
  • 22.

    Baxter EJ, Kulkarni S, Vizmanos JL. Novel translocations that disrupt the platelet-derived growth factor receptor beta (PDGFRB) gene in BCR-ABL-negative chronic myeloproliferative disorders. Br J Haematol 2003;120:251256.

    • Search Google Scholar
    • Export Citation
  • 23.

    Steer EJ, Cross NC. Myeloproliferative disorders with translocations of chromosome 5q31-35: role of the platelet-derived growth factor receptor Beta. Acta Haematol 2002;107:113122.

    • Search Google Scholar
    • Export Citation
  • 24.

    Apperley JF, Gardembas M, Melo JV. Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J Med 2002;347:481487.

    • Search Google Scholar
    • Export Citation
  • 25.

    Magnusson MK, Meade KE, Nakamura R. Activity of STI571 in chronic myelomonocytic leukemia with a platelet-derived growth factor beta receptor fusion oncogene. Blood 2002;100:10881091.

    • Search Google Scholar
    • Export Citation
  • 26.

    Steensma DP, Dewald GW, Lasho TL. The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both ``atypical'' myeloproliferative disorders and myelodysplastic syndromes. Blood 2005;106:12071209.

    • Search Google Scholar
    • Export Citation
  • 27.

    Szpurka H, Tiu R, Murugesan G. Refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T), another myeloproliferative condition characterized by JAK2 V617F mutation. Blood 2006;108:21732181.

    • Search Google Scholar
    • Export Citation
  • 28.

    Ogata K, Nakamura K, Yokose N. Clinical significance of phenotypic features of blasts in patients with myelodysplastic syndrome. Blood 2002;100:38873896.

    • Search Google Scholar
    • Export Citation
  • 29.

    Wells DA, Benesch M, Loken MR. Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation. Blood 2003;102:394403.

    • Search Google Scholar
    • Export Citation
  • 30.

    Gregg XT, Reddy V, Prchal JT. Copper deficiency masquerading as myelodysplastic syndrome. Blood 2002;100:14931495.

  • 31.

    Haddad AS, Subbiah V, Lichtin AE. Hypocupremia and bone marrow failure. Haematologica 2008;93:e15.

  • 32.

    Koca E, Buyukasik Y, Cetiner D. Copper deficiency with increased hematogones mimicking refractory anemia with excess blasts. Leuk Res 2008;32:495499.

    • Search Google Scholar
    • Export Citation
  • 33.

    Prodan CI, Bottomley SS, Vincent AS. Hypocupremia associated with prior vitamin B12 deficiency. Am J Hematol 2007;82:288290.

  • 34.

    Sanz GF, Sanz MA, Greenberg PL. Prognostic factors and scoring systems in myelodysplastic syndromes. Haematologica 1998;83:358368.

  • 35.

    Bennett JM, Catovsky D, Daniel MT. The chronic myeloid leukaemias: guidelines for distinguishing chronic granulocytic, atypical chronic myeloid, and chronic myelomonocytic leukaemia. Proposals by the French-American-British Cooperative Leukaemia Group. Br J Haematol 1994;87:746754.

    • Search Google Scholar
    • Export Citation
  • 36.

    Malcovati L, Porta MG, Pascutto C. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol 2005;23:75947603.

    • Search Google Scholar
    • Export Citation
  • 37.

    Kao JM, McMillan A, Greenberg PL. International MDS risk analysis workshop (IMRAW)/IPSS reanalyzed: impact of cytopenias on clinical outcomes in myelodysplastic syndromes. Am J Hematol 2008;83:765770.

    • Search Google Scholar
    • Export Citation
  • 38.

    Alessandrino EP, Della Porta MG, Bacigalupo A. WHO classification and WPSS predict posttransplantation outcome in patients with myelodysplastic syndrome: a study from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Blood 2008;112:895902.

    • Search Google Scholar
    • Export Citation
  • 39.

    Cermak J, Kacirkova P, Mikulenkova D, Michalova K. Impact of transfusion dependency on survival in patients with early myelodysplastic syndrome without excess of blasts. Leuk Res 2009;33:14691474.

    • Search Google Scholar
    • Export Citation
  • 40.

    Malcovati L, Germing U, Kuendgen A. Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol 2007;25:35033510.

    • Search Google Scholar
    • Export Citation
  • 41.

    Park MJ, Kim HJ, Kim SH. Is International Prognostic Scoring System (IPSS) still standard in predicting prognosis in patients with myelodysplastic syndrome? External validation of the WHO Classification-Based Prognostic Scoring System (WPSS) and comparison with IPSS. Eur J Haematol 2008;81:364373.

    • Search Google Scholar
    • Export Citation
  • 42.

    Cheson BD, Bennett JM, Kantarjian H. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood 2000;96:36713674.

    • Search Google Scholar
    • Export Citation
  • 43.

    Greenberg P, Baer M, Bennett J. NCCN Myelodysplastic Syndromes Guidelines. NCCN Clinical Practice Guidelines in Oncology [Version 1, 2001, CD-ROM]. Rockledge, PA: National Comprehensive Cancer Network, 2001. To view the most recent version of the guideline, go to www.NCCN.org.

    • Search Google Scholar
    • Export Citation
  • 44.

    Greenberg P. The role of hemopoietic growth factors in the treatment of myelodysplastic syndromes. Int J Pediatr Hematol Oncol 1997;4:231238.

    • Search Google Scholar
    • Export Citation
  • 45.

    Greenberg PL. Myelodysplastic syndromes: iron overload consequences and current chelating therapies. J Natl Compr Canc Netw 2006;4:9196.

    • Search Google Scholar
    • Export Citation
  • 46.

    Farquhar MJ, Bowen DT. Oxidative stress and the myelodysplastic syndromes. Int J Hematol 2003;77:342350.

  • 47.

    Hershko C, Link G, Cabantchik I. Pathophysiology of iron overload. Ann N Y Acad Sci 1998;850:191201.

  • 48.

    Jaeger M, Aul C, Sohngen D. [Secondary hemochromatosis in polytransfused patients with myelodysplastic syndromes.] Beitr Infusionsther 1992;30:464468 [in German].

    • Search Google Scholar
    • Export Citation
  • 49.

    Schafer AI, Cheron RG, Dluhy R. Clinical consequences of acquired transfusional iron overload in adults. N Engl J Med 1981;304:319324.

  • 50.

    Malcovati L. Impact of transfusion dependency and secondary iron overload on the survival of patients with myelodysplastic syndromes. Leuk Res 2007;31(Suppl 3):S26.

    • Search Google Scholar
    • Export Citation
  • 51.

    Brittenham GM, Badman DG. Noninvasive measurement of iron: report of an NIDDK workshop. Blood 2003;101:1519.

  • 52.

    St Pierre TG, Clark PR, Chua-anusorn W. Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood 2005;105:855861.

    • Search Google Scholar
    • Export Citation
  • 53.

    Jensen PD, Heickendorff L, Pedersen B. The effect of iron chelation on haemopoiesis in MDS patients with transfusional iron overload. Br J Haematol 1996;94:288299.

    • Search Google Scholar
    • Export Citation
  • 54.

    Jensen PD, Jensen FT, Christensen T. Evaluation of myocardial iron by magnetic resonance imaging during iron chelation therapy with deferrioxamine: indication of close relation between myocardial iron content and chelatable iron pool. Blood 2003;101:46324639.

    • Search Google Scholar
    • Export Citation
  • 55.

    Cohen AR, Galanello R, Piga A. Safety and effectiveness of long-term therapy with the oral iron chelator deferiprone. Blood 2003;102:15831587.

    • Search Google Scholar
    • Export Citation
  • 56.

    Nisbet-Brown E, Olivieri NF, Giardina PJ. Effectiveness and safety of ICL670 in iron-loaded patients with thalassaemia: a randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet 2003;361:15971602.

    • Search Google Scholar
    • Export Citation
  • 57.

    Piga A, Galanello R, Cappellini MD. Phase II study of ICL670, an oral chelator, in adult thalassaemia patients with transfusional iron overload: efficacy, safety, pharmaco kinetics (PK) and pharmacodynamics (PD) after 18 months of therapy [abstract]. Blood 2003;102:Abstract 412.

    • Search Google Scholar
    • Export Citation
  • 58.

    Olivieri NF, Koren G, Hermann C. Comparison of oral iron chelator L1 and desferrioxamine in iron-loaded patients. Lancet 1990;336:12751279.

  • 59.

    Greenberg P, Rigsby CK, Stone RM. NCCN Task Force Report: transfusion and iron overload in patients with myelodysplastic syndromes. Available at: http://www.nccn.org/JNCCN/PDF/2009_Transfussion_MDS_TF.pdf. Accessed November 22, 2010.

    • Search Google Scholar
    • Export Citation
  • 60.

    Kantarjian H, Issa JP, Rosenfeld CS. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer 2006;106:17941803.

    • Search Google Scholar
    • Export Citation
  • 61.

    Silverman LR, Demakos EP, Peterson BL. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 2002;20:24292440.

    • Search Google Scholar
    • Export Citation
  • 62.

    Silverman LR, McKenzie DR, Peterson BL. Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J Clin Oncol 2006;24:38953903.

    • Search Google Scholar
    • Export Citation
  • 63.

    Fenaux P, Mufti GJ, Hellstrom-Lindberg E. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol 2009;10:223232.

    • Search Google Scholar
    • Export Citation
  • 64.

    Lubbert M, Wijermans P, Kunzmann R. Cytogenetic responses in high-risk myelodysplastic syndrome following low-dose treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine. Br J Haematol 2001;114:349357.

    • Search Google Scholar
    • Export Citation
  • 65.

    Wijermans P, Lubbert M, Verhoef G. Low-dose 5-aza-2'-deoxycytidine, a DNA hypomethylating agent, for the treatment of high-risk myelodysplastic syndrome: a multicenter phase II study in elderly patients. J Clin Oncol 2000;18:956962.

    • Search Google Scholar
    • Export Citation
  • 66.

    Saba H, Rosenfeld C, Issa JP. First report of the phase III north American trial of decitabine in advanced myelodysplastic syndrome (MDS) [abstract]. Blood 2004;104:Abstract 67.

    • Search Google Scholar
    • Export Citation
  • 67.

    van den Bosch J, Lubbert M, Verhoef G, Wijermans PW. The effects of 5-aza-2'-deoxycytidine (Decitabine) on the platelet count in patients with intermediate and high-risk myelodysplastic syndromes. Leuk Res 2004;28:785790.

    • Search Google Scholar
    • Export Citation
  • 68.

    Saba HI, Lubbert M, Wijermans PW. Response rates of phase 2 and phase 3 trials of decitabine (DAC) in patients with myelodysplastic syndromes (MDS) [abstract]. Blood 2005;106:Abstract 2515.

    • Search Google Scholar
    • Export Citation
  • 69.

    Kantarjian H, O'Brien S, Giles F. Decitabine low-dose schedule (100 mg/m2/Course) in myelodysplastic syndrome (MDS). Comparison of 3 different dose schedules [abstract]. Blood 2005;106:Asbtract 2522.

    • Search Google Scholar
    • Export Citation
  • 70.

    Kantarjian HM, O'Brien S, Shan J. Update of the decitabine experience in higher risk myelodysplastic syndrome and analysis of prognostic factors associated with outcome. Cancer 2007;109:265273.

    • Search Google Scholar
    • Export Citation
  • 71.

    Kantarjian H, Oki Y, Garcia-Manero G. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 2007;109:5257.

    • Search Google Scholar
    • Export Citation
  • 72.

    Deeg HJ, Gotlib J, Beckham C. Soluble TNF receptor fusion protein (etanercept) for the treatment of myelodysplastic syndrome: a pilot study. Leukemia 2002;16:162164.

    • Search Google Scholar
    • Export Citation
  • 73.

    Deeg HJ, Jiang PY, Holmberg LA. Hematologic responses of patients with MDS to antithymocyte globulin plus etanercept correlate with improved flow scores of marrow cells. Leuk Res 2004;28:11771180.

    • Search Google Scholar
    • Export Citation
  • 74.

    Jonásová A, Neuwirtová R, Cermák J. 164 Promising cyclosporin a therapy for myelodysplastic syndrome. Leuk Res 1997;21:S5353.

  • 75.

    Molldrem JJ, Caples M, Mavroudis D. Antithymocyte globulin for patients with myelodysplastic syndrome. Br J Haematol 1997;99:699705.

  • 76.

    Raza A, Meyer P, Dutt D. Thalidomide produces transfusion independence in long-standing refractory anemias of patients with myelodysplastic syndromes. Blood 2001;98:958965.

    • Search Google Scholar
    • Export Citation
  • 77.

    Strupp C, Germing U, Aivado M. Thalidomide for the treatment of patients with myelodysplastic syndromes. Leukemia 2002;16:16.

  • 78.

    Sloand EM, Wu CO, Greenberg P. Factors affecting response and survival in patients with myelodysplasia treated with immunosuppressive therapy. J Clin Oncol 2008;26:25052511.

    • Search Google Scholar
    • Export Citation
  • 79.

    List A, Kurtin S, Roe DJ. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 2005;352:549557.

  • 80.

    Nimer SD. Clinical management of myelodysplastic syndromes with interstitial deletion of chromosome 5q. J Clin Oncol 2006;24:25762582.

    • Search Google Scholar
    • Export Citation
  • 81.

    Raza A, Reeves JA, Feldman EJ. Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1 risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood 2008;111:86–-93.

    • Search Google Scholar
    • Export Citation
  • 82.

    Tricot G, Boogaerts MA. The role of aggressive chemotherapy in the treatment of the myelodysplastic syndromes. Br J Haematol 1986;63:477483.

    • Search Google Scholar
    • Export Citation
  • 83.

    Estey EH, Thall PF, Cortes JE. Comparison of idarubicin + ara-C-, fludarabine + ara-C-, and topotecan + ara-C-based regimens in treatment of newly diagnosed acute myeloid leukemia, refractory anemia with excess blasts in transformation, or refractory anemia with excess blasts. Blood 2001;98:35753583.

    • Search Google Scholar
    • Export Citation
  • 84.

    Sonneveld P, van Dongen JJ, Hagemeijer A. High expression of the multidrug resistance P-glycoprotein in high-risk myelodysplasia is associated with immature phenotype. Leukemia 1993;7:963969.

    • Search Google Scholar
    • Export Citation
  • 85.

    Advani R, Saba HI, Tallman MS. Treatment of refractory and relapsed acute myelogenous leukemia with combination chemotherapy plus the multidrug resistance modulator PSC 833 (Valspodar). Blood 1999;93:787795.

    • Search Google Scholar
    • Export Citation
  • 86.

    Wattel E, Solary E, Hecquet B. Quinine improves results of intensive chemotherapy (IC) in myelodysplastic syndromes (MDS) expressing P-glycoprotein (PGP). Updated results of a randomized study. Groupe Francais des Myelodysplasies (GFM) and Groupe GOELAMS. Adv Exp Med Biol 1999;457:3546.

    • Search Google Scholar
    • Export Citation
  • 87.

    Greenberg PL, Lee SJ, Advani R. Mitoxantrone, etoposide, and cytarabine with or without valspodar in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome: a phase III trial (E2995). J Clin Oncol 2004;22:10781086.

    • Search Google Scholar
    • Export Citation
  • 88.

    Anderson JE, Appelbaum FR, Fisher LD. Allogeneic bone marrow transplantation for 93 patients with myelodysplastic syndrome. Blood 1993;82:677681.

    • Search Google Scholar
    • Export Citation
  • 89.

    De Witte T, Zwaan F, Hermans J. Allogeneic bone marrow transplantation for secondary leukaemia and myelodysplastic syndrome: a survey by the Leukaemia Working Party of the European Bone Marrow Transplantation Group (EBMTG). Br J Haematol 1990;74:151155.

    • Search Google Scholar
    • Export Citation
  • 90.

    Demuynck H, Verhoef GE, Zachee P. Treatment of patients with myelodysplastic syndromes with allogeneic bone marrow transplantation from genotypically HLA-identical sibling and alternative donors. Bone Marrow Transplant 1996;17:745751.

    • Search Google Scholar
    • Export Citation
  • 91.

    Jurado M, Deeg HJ, Storer B. Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome after conditioning with busulfan and fractionated total body irradiation is associated with low relapse rate but considerable nonrelapse mortality. Biol Blood Marrow Transplant 2002;8:161169.

    • Search Google Scholar
    • Export Citation
  • 92.

    Kerbauy DM, Chyou F, Gooley T. Allogeneic hematopoietic cell transplantation for chronic myelomonocytic leukemia. Biol Blood Marrow Transplant 2005;11:713720.

    • Search Google Scholar
    • Export Citation
  • 93.

    Nevill TJ, Fung HC, Shepherd JD. Cytogenetic abnormalities in primary myelodysplastic syndrome are highly predictive of outcome after allogeneic bone marrow transplantation. Blood 1998;92:19101917.

    • Search Google Scholar
    • Export Citation
  • 94.

    Scott BL, Sandmaier BM, Storer B. Myeloablative vs nonmyeloablative allogeneic transplantation for patients with myelodysplastic syndrome or acute myelogenous leukemia with multilineage dysplasia: a retrospective analysis. Leukemia 2006;20:128135.

    • Search Google Scholar
    • Export Citation
  • 95.

    Wallen H, Gooley TA, Deeg HJ. Ablative allogeneic hematopoietic cell transplantation in adults 60 years of age and older. J Clin Oncol 2005;23:34393446.

    • Search Google Scholar
    • Export Citation
  • 96.

    Anderson J, Thomas ED. The Seattle experience with bone marrow transplantation for MDS. Leuk Res 1997;21(Suppl 1):S51.

  • 97.

    de Lima M, Anagnostopoulos A, Munsell M. Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. Blood 2004;104:865872.

    • Search Google Scholar
    • Export Citation
  • 98.

    Giralt S, Estey E, Albitar M. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood 1997;89:45314536.

    • Search Google Scholar
    • Export Citation
  • 99.

    Anderson JE, Anasetti C, Appelbaum FR. Unrelated donor marrow transplantation for myelodysplasia (MDS) and MDS-related acute myeloid leukaemia. Br J Haematol 1996;93:5967.

    • Search Google Scholar
    • Export Citation
  • 100.

    Castro-Malaspina H, Harris RE, Gajewski J. Unrelated donor marrow transplantation for myelodysplastic syndromes: outcome analysis in 510 transplants facilitated by the National Marrow Donor Program. Blood 2002;99:19431951.

    • Search Google Scholar
    • Export Citation
  • 101.

    Deeg H. Optimization of transplant regimens for patients with myelodysplastic syndromes (MDS). In: Hematology 2005: American Society of Hematology Education Program Book. Washington, DC: American Society of Hematology; 2005:167173.

    • Search Google Scholar
    • Export Citation
  • 102.

    De Witte T, Suciu S, Verhoef G. Intensive chemotherapy followed by allogeneic or autologous stem cell transplantation for patients with myelodysplastic syndromes (MDSs) and acute myeloid leukemia following MDS. Blood 2001;98:23262331.

    • Search Google Scholar
    • Export Citation
  • 103.

    Fukumoto JS, Greenberg PL. Management of patients with higher risk myelodysplastic syndromes. Crit Rev Oncol Hematol 2005;56:179192.

  • 104.

    Alyea EP, Kim HT, Ho V. Comparative outcome of nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation for patients older than 50 years of age. Blood 2005;105:18101814.

    • Search Google Scholar
    • Export Citation
  • 105.

    Cutler CS, Lee SJ, Greenberg P. A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome. Blood 2004;104:579585.

    • Search Google Scholar
    • Export Citation
  • 106.

    Laport GG, Sandmaier BM, Storer BE. Reduced-intensity conditioning followed by allogeneic hematopoietic cell transplantation for adult patients with myelodysplastic syndrome and myeloproliferative disorders. Biol Blood Marrow Transplant 2008;14:246255.

    • Search Google Scholar
    • Export Citation
  • 107.

    McClune B, Weisdorf DJ, DiPersio JF. Non-myeloablative hematopoietic stem cell transplantation in older patients with AML and MDS: Results from the center for International Blood and Marrow Transplant Research (CIBMTR) [abstract]. Blood 2008;112:Abstract 346.

    • Search Google Scholar
    • Export Citation
  • 108.

    Kindwall-Keller T, Isola LM. The evolution of hematopoietic SCT in myelodysplastic syndrome. Bone Marrow Transplant 2009;43:597609.

  • 109.

    Oliansky DM, Antin JH, Bennett JM. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of myelodysplastic syndromes: an evidence-based review. Biol Blood Marrow Transplant 2009;15:137172.

    • Search Google Scholar
    • Export Citation
  • 110.

    Deeg H, Sandmaier BM. Who is fit for allogeneic transplantation? Blood 2010;116:47624770.

  • 111.

    Beran M, Shen Y, Kantarjian H. High-dose chemotherapy in high-risk myelodysplastic syndrome: covariate-adjusted comparison of five regimens. Cancer 2001;92:19992015.

    • Search Google Scholar
    • Export Citation
  • 112.

    WijerMans P, Suciu S, Baila L. Low dose decitabine versus best supportive care in elderly patients with intermediate or high risk MDS not eligible for intensive chemotherapy: final results of the randomized phase III study (06011) of the EORTC leukemia and German MDS study groups [abstract]. Blood 2008;112:Abstract 226.

    • Search Google Scholar
    • Export Citation
  • 113.

    Jacobs A, Janowska-Wieczorek A, Caro J. Circulating erythropoietin in patients with myelodysplastic syndromes. Br J Haematol 1989;73:3639.

  • 114.

    Hellstrom-Lindberg E. Efficacy of erythropoietin in the myelodysplastic syndromes: a meta-analysis of 205 patients from 17 studies. Br J Haematol 1995;89:6771.

    • Search Google Scholar
    • Export Citation
  • 115.

    Negrin RS, Stein R, Doherty K. Maintenance treatment of the anemia of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor and erythropoietin: evidence for in vivo synergy. Blood 1996;87:40764081.

    • Search Google Scholar
    • Export Citation
  • 116.

    Casadevall N, Durieux P, Dubois S. Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial. Blood 2004;104:321327.

    • Search Google Scholar
    • Export Citation
  • 117.

    Hellstrom-Lindberg E, Ahlgren T, Beguin Y. Treatment of anemia in myelodysplastic syndromes with granulocyte colony-stimulating factor plus erythropoietin: results from a randomized phase II study and long-term follow-up of 71 patients. Blood 1998;92:6875.

    • Search Google Scholar
    • Export Citation
  • 118.

    Hellstrom-Lindberg E, Negrin R, Stein R. Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model. Br J Haematol 1997;99:344351.

    • Search Google Scholar
    • Export Citation
  • 119.

    Spiriti MA, Latagliata R, Niscola P. Impact of a new dosing regimen of epoetin alfa on quality of life and anemia in patients with low-risk myelodysplastic syndrome. Ann Hematol 2005;84:167176.

    • Search Google Scholar
    • Export Citation
  • 120.

    Hellstrom-Lindberg E, Gulbrandsen N, Lindberg G. A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life. Br J Haematol 2003;120:10371046.

    • Search Google Scholar
    • Export Citation
  • 121.

    Mannone L, Gardin C, Quarre MC. High-dose darbepoetin alpha in the treatment of anaemia of lower risk myelodysplastic syndrome results of a phase II study. Br J Haematol 2006;133:513519.

    • Search Google Scholar
    • Export Citation
  • 122.

    Musto P, Lanza F, Balleari E. Darbepoetin alpha for the treatment of anaemia in low-intermediate risk myelodysplastic syndromes. Br J Haematol 2005;128:204209.

    • Search Google Scholar
    • Export Citation
  • 123.

    Giraldo P, Nomdedeu B, Loscertales J. Darbepoetin alpha for the treatment of anemia in patients with myelodysplastic syndromes. Cancer 2006;107:28072816.

    • Search Google Scholar
    • Export Citation
  • 124.

    Stasi R, Abruzzese E, Lanzetta G. Darbepoetin alfa for the treatment of anemic patients with low- and intermediate-1-risk myelodysplastic syndromes. Ann Oncol 2005;16:19211927.

    • Search Google Scholar
    • Export Citation
  • 125.

    Greenberg PL, Sun Z, Miller KB. Treatment of myelodysplastic syndromes patients with erythropoietin with or without granulocyte colony-stimulating factor: results of a prospective randomized phase III trial by the Eastern Cooperative Oncology Group (E1996). Blood 2009;114:23932400.

    • Search Google Scholar
    • Export Citation
  • 126.

    Jadersten M, Malcovati L, Dybedal I. Erythropoietin and granulocyte-colony stimulating factor treatment associated with improved survival in myelodysplastic syndrome. J Clin Oncol 2008;26:36073613.

    • Search Google Scholar
    • Export Citation
  • 127.

    Park S, Grabar S, Kelaidi C. Predictive factors of response and survival in myelodysplastic syndrome treated with erythropoietin and G-CSF: the GFM experience. Blood 2008;111:574582.

    • Search Google Scholar
    • Export Citation
  • 128.

    Kornblith AB, Herndon JE II, Silverman LR. Impact of azacytidine on the quality of life of patients with myelodysplastic syndrome treated in a randomized phase III trial: a Cancer and Leukemia Group B study. J Clin Oncol 2002;20:24412452.

    • Search Google Scholar
    • Export Citation
  • 129.

    Thomas M. Health-related quality of life for those with myelodysplastic syndrome: conceptualization, measurement and implications. In: Greenberg PL, ed. Myelodysplastic Syndromes: Clinical and Biological Advances. Cambridge, England: Cambridge University Press; 2006:263295

    • Search Google Scholar
    • Export Citation
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