The myelodysplastic syndromes (MDS) comprise a heterogenous group of myeloid disorders with a highly variable disease course. Diagnostic criteria to better stratify patients with MDS continue to evolve, based on morphology, cytogenetics, and the presence of cytopenias. More accurate classification of patients will allow for better treatment guidance. Treatment encompasses supportive care, treatment of anemia, low-intensity therapy, and high-intensity therapy. This portion of the guidelines focuses on diagnostic classification, molecular abnormalities, therapeutic options, and recommended treatment approaches.

  • 1.

    National Cancer Institute. SEER cancer statistics review 1975-2013: myelodysplastic syndromes (MDS) chronic myeloproliferative disorders (CMD) and chronic myelomonocytic leukemia (CMML). 2016. Available at: http://seer.cancer.gov/csr/1975_2013/browse_csr.php?sectionSEL=30&pageSEL=sect_30_intro.01.html. Accessed November 8 2016.

    • Search Google Scholar
    • Export Citation
  • 2.

    MaXDoesMRazaAMayneST. Myelodysplastic syndromes: incidence and survival in the United States. Cancer2007;109:15361542.

  • 3.

    GreenbergP. The myelodysplastic syndromes. In: HoffmanRBenzEShattilS eds. Hematology: Basic Principles and Practice3rd ed.New York, NY: Churchill Livingstone; 2000;11061129.

    • Search Google Scholar
    • Export Citation
  • 4.

    KaloutsiVKohlmeyerUMaschekH. 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 Pathol1994;101:123129.

    • Search Google Scholar
    • Export Citation
  • 5.

    ValentPHornyHPBennettJM. Definitions and standards in the diagnosis and treatment of the myelodysplastic syndromes: consensus statements and report from a working conference. Leuk Res2007;31:727736.

    • Search Google Scholar
    • Export Citation
  • 6.

    ArberDAOraziAHasserjianR. The 2016 revision to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia. Blood2016;127:23912405.

    • Search Google Scholar
    • Export Citation
  • 7.

    GreenbergPLTuechlerHSchanzJ. Cytopenia levels for aiding establishment of the diagnosis of myelodysplastic syndromes. Blood2016;128:20962097.

    • Search Google Scholar
    • Export Citation
  • 8.

    BrunningRBennettJFlandrinG. Myelodysplastic syndromes. In: JaffeEHarrisNSteinH eds. WHO Classification of Tumours: Pathology and Genetics of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001:6173.

    • Search Google Scholar
    • Export Citation
  • 9.

    HarrisNLJaffeESDieboldJ. 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 Oncol1999;17:38353849.

    • Search Google Scholar
    • Export Citation
  • 10.

    VardimanJWHarrisNLBrunningRD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood2002;100:22922302.

  • 11.

    BrunningROraziAGermingU. Myelodysplastic syndromes. In: SwerdlowSHCampoEHarrisNL eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues4th ed.Lyon, France: IARC Press; 2008;87104.

    • Search Google Scholar
    • Export Citation
  • 12.

    VardimanJWThieleJArberDA. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood2009;114:937951.

    • Search Google Scholar
    • Export Citation
  • 13.

    SchanzJTuchlerHSoleF. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J Clin Oncol2012;30:820829.

    • Search Google Scholar
    • Export Citation
  • 14.

    GermingULausekerMHildebrandtB. Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): a multicenter study. Leukemia2012;26:12861292.

    • Search Google Scholar
    • Export Citation
  • 15.

    MalloMCerveraJSchanzJ. Impact of adjunct cytogenetic abnormalities for prognostic stratification in patients with myelodysplastic syndrome and deletion 5q. Leukemia2011;25:110120.

    • Search Google Scholar
    • Export Citation
  • 16.

    ArberDABrunningRDOraziA. Acute myeloid leukaemia with myelodysplastia-related changes. In: SwerdlowSHCampoEHarrisNL. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues4th ed.Lyon, France: IARC Press; 2008:124126.

    • Search Google Scholar
    • Export Citation
  • 17.

    HasserjianRPCampigottoFKlepeisV. De novo acute myeloid leukemia with 20-29% blasts is less aggressive than acute myeloid leukemia with >/=30% blasts in older adults: a Bone Marrow Pathology Group study. Am J Hematol2014;89:e193199.

    • Search Google Scholar
    • Export Citation
  • 18.

    AlbitarMManshouriTShenY. Myelodysplastic syndrome is not merely “preleukemia”. Blood2002;100:791798.

  • 19.

    GreenbergPAndersonJde WitteT. Problematic WHO reclassification of myelodysplastic syndromes. Clin Oncol2000;18:34473452.

  • 20.

    GermingUGattermannNStruppC. Validation of the WHO proposals for a new classification of primary myelodysplastic syndromes: a retrospective analysis of 1600 patients. Leuk Res2000;24:983992.

    • Search Google Scholar
    • Export Citation
  • 21.

    GermingUStruppCKuendgenA. Refractory anaemia with excess of blasts (RAEB): analysis of reclassification according to the WHO proposals. Br J Haematol2006;132:162167.

    • Search Google Scholar
    • Export Citation
  • 22.

    GermingUStruppCKuendgenA. Prospective validation of the WHO proposals for the classification of myelodysplastic syndromes. Haematologica2006;91:15961604.

    • Search Google Scholar
    • Export Citation
  • 23.

    MalcovatiLPortaMGPascuttoC. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol2005;23:75947603.

    • Search Google Scholar
    • Export Citation
  • 24.

    Muller-BerndorffHHaasPSKunzmannR. Comparison of five prognostic scoring systems, the French-American-British (FAB) and World Health Organization (WHO) classifications in patients with myelodysplastic syndromes: results of a single-center analysis. Ann Hematol2006;85:502513.

    • Search Google Scholar
    • Export Citation
  • 25.

    GreenbergPCoxCLeBeauMM. International scoring system for evaluating prognosis in myelodysplastic syndromes[published correction appears in Blood 1998;2091:1100]. Blood1997;89:20792088.

    • Search Google Scholar
    • Export Citation
  • 26.

    ListADewaldGBennettJ. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med2006;355:14561465.

  • 27.

    TaskesenEHavermansMvan LomK. Two splice-factor mutant leukemia subgroups uncovered at the boundaries of MDS and AML using combined gene expression and DNA-methylation profiling. Blood2014;123:33273335.

    • Search Google Scholar
    • Export Citation
  • 28.

    LindsleyRCMarBGMazzolaE. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood2015;125:13671376.

  • 29.

    SwerdlowSHCampoEHarrisNL. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues4th ed.Lyon, France: IARC Press; 2008.

  • 30.

    WangSAHasserjianRPFoxPS. Atypical chronic myeloid leukemia is clinically distinct from unclassifiable myelodysplastic/myeloproliferative neoplasms. Blood2014;123:26452651.

    • Search Google Scholar
    • Export Citation
  • 31.

    MeggendorferMBacherUAlpermannT. SETBP1 mutations occur in 9% of MDS/MPN and in 4% of MPN cases and are strongly associated with atypical CML, monosomy 7, isochromosome i(17)(q10), ASXL1 and CBL mutations. Leukemia2013;27:18521860.

    • Search Google Scholar
    • Export Citation
  • 32.

    PiazzaRVallettaSWinkelmannN. Recurrent SETBP1 mutations in atypical chronic myeloid leukemia. Nat Genet2013;45:1824.

  • 33.

    Gambacorti-PasseriniCBDonadoniCParmianiA. Recurrent ETNK1 mutations in atypical chronic myeloid leukemia. Blood2015;125:499503.

  • 34.

    SakaguchiHOkunoYMuramatsuH. Exome sequencing identifies secondary mutations of SETBP1 and JAK3 in juvenile myelomonocytic leukemia. Nat Genet2013;45:937941.

    • Search Google Scholar
    • Export Citation
  • 35.

    VardimanJWBennettJMBainBJ. Myelodysplastic/myeloproliferative neoplasm, unclassifiable. In: SwerdlowSHCampoEHarrisNL. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues4th ed.Lyon, France: IARC Press; 2008:8586.

    • Search Google Scholar
    • Export Citation
  • 36.

    PapaemmanuilECazzolaMBoultwoodJ. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N Engl J Med2011;365:13841395.

  • 37.

    MalcovatiLPapaemmanuilEBowenDT. Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms. Blood2011;118:62396246.

    • Search Google Scholar
    • Export Citation
  • 38.

    BejarRStevensonKECaugheyBA. Validation of a prognostic model and the impact of mutations in patients with lower-risk myelodysplastic syndromes. J Clin Oncol2012;30:33763382.

    • Search Google Scholar
    • Export Citation
  • 39.

    CazzolaMRossiMMalcovatiL. Biologic and clinical significance of somatic mutations of SF3B1 in myeloid and lymphoid neoplasms. Blood2013;121:260269.

    • Search Google Scholar
    • Export Citation
  • 40.

    XieMLuCWangJ. Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med2014;20:14721478.

  • 41.

    JaiswalSFontanillasPFlannickJ. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med2014;371:24882498.

  • 42.

    CargoCARowbothamNEvansPA. Targeted sequencing identifies patients with preclinical MDS at high risk of disease progression. Blood2015;126:23622365.

    • Search Google Scholar
    • Export Citation
  • 43.

    KwokBHallJMWitteJS. MDS-associated somatic mutations and clonal hematopoiesis are common in idiopathic cytopenias of undetermined significance. Blood2015;126:23552361.

    • Search Google Scholar
    • Export Citation
  • 44.

    BejarRStevensonKAbdel-WahabO. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med2011;364:24962506.

  • 45.

    PapaemmanuilEGerstungMMalcovatiL. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood2013;122:36163627.

    • Search Google Scholar
    • Export Citation
  • 46.

    HaferlachTNagataYGrossmannV. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia2014;28:241247.

  • 47.

    ItzyksonRKosmiderORennevilleA. Prognostic score including gene mutations in chronic myelomonocytic leukemia. J Clin Oncol2013;31:24282436.

    • Search Google Scholar
    • Export Citation
  • 48.

    PatnaikMMItzyksonRLashoTL. ASXL1 and SETBP1 mutations and their prognostic contribution in chronic myelomonocytic leukemia: a two-center study of 466 patients. Leukemia2014;28:22062212.

    • Search Google Scholar
    • Export Citation
  • 49.

    WalterMJDingLShenD. Recurrent DNMT3A mutations in patients with myelodysplastic syndromes. Leukemia2011;25:11531158.

  • 50.

    GraubertTAShenDDingL. Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes. Nat Genet2012;44:5357.

  • 51.

    TholFKadeSSchlarmannC. Frequency and prognostic impact of mutations in SRSF2, U2AF1, and ZRSR2 in patients with myelodysplastic syndromes. Blood2012;119:35783584.

    • Search Google Scholar
    • Export Citation
  • 52.

    MakishimaHYoshidaKNguyenN. Somatic SETBP1 mutations in myeloid malignancies. Nat Genet2013;45:942946.

  • 53.

    PatnaikMMLashoTLHodnefieldJM. SF3B1 mutations are prevalent in myelodysplastic syndromes with ring sideroblasts but do not hold independent prognostic value. Blood2012;119:569572.

    • Search Google Scholar
    • Export Citation
  • 54.

    ItzyksonRKosmiderOCluzeauT. Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias. Leukemia2011;25:11471152.

    • Search Google Scholar
    • Export Citation
  • 55.

    BejarRLordAStevensonK. TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. Blood2014;124:27052712.

    • Search Google Scholar
    • Export Citation
  • 56.

    SebaaAAdesLBaran-MarzackF. Incidence of 17p deletions and TP53 mutation in myelodysplastic syndrome and acute myeloid leukemia with 5q deletion. Genes Chromosomes Cancer2012;51:10861092.

    • Search Google Scholar
    • Export Citation
  • 57.

    JaderstenMSaftLSmithA. TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. J Clin Oncol2011;29:19711979.

    • Search Google Scholar
    • Export Citation
  • 58.

    MalloMDel ReyMIbanezM. Response to lenalidomide in myelodysplastic syndromes with del(5q): influence of cytogenetics and mutations. Br J Haematol2013;162:7486.

    • Search Google Scholar
    • Export Citation
  • 59.

    JaderstenMSaftLPellagattiA. Clonal heterogeneity in the 5q-syndrome: p53 expressing progenitors prevail during lenalidomide treatment and expand at disease progression. Haematologica2009;94:17621766.

    • Search Google Scholar
    • Export Citation
  • 60.

    MohamedaliAMAlkhatabiHKulasekararajA. Utility of peripheral blood for cytogenetic and mutation analysis in myelodysplastic syndrome. Blood2013;122:567570.

    • Search Google Scholar
    • Export Citation
  • 61.

    ChesonBDBennettJMKantarjianH. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood2000;96:36713674.

    • Search Google Scholar
    • Export Citation
  • 62.

    ChesonBDGreenbergPLBennettJM. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood2006;108:419425.

    • Search Google Scholar
    • Export Citation
  • 63.

    GreenbergPBaerMBennettJ. NCCN Practice Guidelines for Myelodysplastic Syndromes, Version1, 2001. The Complete Library of NCCN Guidelines [CD-ROM]. Rockledge, PA; 2001.

    • Search Google Scholar
    • Export Citation
  • 64.

    GreenbergPLTuechlerHSchanzJ. Revised International Prognostic Scoring System (IPSS-R) for myelodysplastic syndromes. Blood2012;120:24542465.

    • Search Google Scholar
    • Export Citation
  • 65.

    MannoneLGardinCQuarreMC. High-dose darbepoetin alpha in the treatment of anaemia of lower risk myelodysplastic syndrome results of a phase II study. Br J Haematol2006;133:513519.

    • Search Google Scholar
    • Export Citation
  • 66.

    MustoPLanzaFBalleariE. Darbepoetin alpha for the treatment of anaemia in low-intermediate risk myelodysplastic syndromes. Br J Haematol2005;128:204209.

    • Search Google Scholar
    • Export Citation
  • 67.

    GiraldoPNomdedeuBLoscertalesJ. Darbepoetin alpha for the treatment of anemia in patients with myelodysplastic syndromes. Cancer2006;107:28072816.

    • Search Google Scholar
    • Export Citation
  • 68.

    StasiRAbruzzeseELanzettaG. Darbepoetin alfa for the treatment of anemic patients with low- and intermediate-1-risk myelodysplastic syndromes. Ann Oncol2005;16:19211927.

    • Search Google Scholar
    • Export Citation
  • 69.

    Hellstrom-LindbergEAhlgrenTBeguinY. 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. Blood1998;92:6875.

    • Search Google Scholar
    • Export Citation
  • 70.

    JaderstenMMalcovatiLDybedalI. Erythropoietin and granulocyte-colony stimulating factor treatment associated with improved survival in myelodysplastic syndrome. J Clin Oncol2008;26:36073613.

    • Search Google Scholar
    • Export Citation
  • 71.

    ParkSGrabarSKelaidiC. Predictive factors of response and survival in myelodysplastic syndrome treated with erythropoietin and G-CSF: the GFM experience. Blood2008;111:574582.

    • Search Google Scholar
    • Export Citation
  • 72.

    KelaidiCBeyne-RauzyOBraunT. High response rate and improved exercise capacity and quality of life with a new regimen of darbepoetin alfa with or without filgrastim in lower-risk myelodysplastic syndromes: a phase II study by the GFM. Ann Hematol2013;92:621631.

    • Search Google Scholar
    • Export Citation
  • 73.

    TehranchiRFadeelBSchmidt-MendeJ. Antiapoptotic role of growth factors in the myelodysplastic syndromes: concordance between in vitro and in vivo observations. Clin Cancer Res2005;11:62916299.

    • Search Google Scholar
    • Export Citation
  • 74.

    KelaidiCParkSBrechignacS. Treatment of myelodysplastic syndromes with 5q deletion before the lenalidomide era; the GFM experience with EPO and thalidomide. Leuk Res2008;32:10491053.

    • Search Google Scholar
    • Export Citation
  • 75.

    GreenbergPLSunZMillerKB. 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). Blood2009;114:23932400.

    • Search Google Scholar
    • Export Citation
  • 76.

    PhurroughSJacquesLCiccantiM. Decision memo for erythropoiesis stimulating agents (ESAs) for non-renal disease indications (CAG-00383N). Available at: https://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=203&ver=12&NcaName=Erythropoiesis+Stimulating+Agents+&bc=BEAAAAAAIAAA. Accessed December 19 2017.

    • Search Google Scholar
    • Export Citation
  • 77.

    FenauxPMuftiGJHellstrom-LindbergE. 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 Oncol2009;10:223232.

    • Search Google Scholar
    • Export Citation
  • 78.

    KantarjianHIssaJPRosenfeldCS. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer2006;106:17941803.

    • Search Google Scholar
    • Export Citation
  • 79.

    LubbertMSuciuSBailaL. Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group. J Clin Oncol2011;29:19871996.

    • Search Google Scholar
    • Export Citation
  • 80.

    SilvermanLRDemakosEPPetersonBL. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the Cancer and Leukemia Broup B. J Clin Oncol2002;20:24292440.

    • Search Google Scholar
    • Export Citation
  • 81.

    SilvermanLRMcKenzieDRPetersonBL. 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 Oncol2006;24:38953903.

    • Search Google Scholar
    • Export Citation
  • 82.

    SilvermanLRFenauxPMuftiGJ. Continued azacitidine therapy beyond time of first response improves quality of response in patients with higher-risk myelodysplastic syndromes. Cancer2011;117:26972702.

    • Search Google Scholar
    • Export Citation
  • 83.

    LyonsRMCosgriffTMModiSS. Hematologic response to three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes. J Clin Oncol2009;27:18501856.

    • Search Google Scholar
    • Export Citation
  • 84.

    MartinMGWalgrenRAProcknowE. A phase II study of 5-day intravenous azacitidine in patients with myelodysplastic syndromes. Am J Hematol2009;84:560564.

    • Search Google Scholar
    • Export Citation
  • 85.

    LubbertMWijermansPKunzmannR. Cytogenetic responses in high-risk myelodysplastic syndrome following low-dose treatment with the DNA methylation inhibitor 5-aza-2’-deoxycytidine. Br J Haematol2001;114:349357.

    • Search Google Scholar
    • Export Citation
  • 86.

    WijermansPLubbertMVerhoefG. 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 Oncol2000;18:956962.

    • Search Google Scholar
    • Export Citation
  • 87.

    van den BoschJLubbertMVerhoefGWijermansPW. The effects of 5-aza-2’-deoxycytidine (decitabine) on the platelet count in patients with intermediate and high-risk myelodysplastic syndromes. Leuk Res2004;28:785790.

    • Search Google Scholar
    • Export Citation
  • 88.

    SabaHILubbertMWijermansPW. Response rates of phase 2 and phase 3 trials of decitabine (DAC) in patients with myelodysplastic syndromes (MDS) [abstract]. Blood2005;106:2515.

    • Search Google Scholar
    • Export Citation
  • 89.

    KantarjianHMO'BrienSShanJ. Update of the decitabine experience in higher risk myelodysplastic syndrome and analysis of prognostic factors associated with outcome. Cancer2007;109:265273.

    • Search Google Scholar
    • Export Citation
  • 90.

    KantarjianHOkiYGarcia-ManeroG. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood2007;109:5257.

    • Search Google Scholar
    • Export Citation
  • 91.

    DamajGDuhamelARobinM. Impact of azacitidine before allogeneic stem-cell transplantation for myelodysplastic syndromes: a study by the Societe Francaise de Greffe de Moelle et de Therapie-Cellulaire and the Groupe-Francophone des Myelodysplasies. J Clin Oncol2012;30:45334540.

    • Search Google Scholar
    • Export Citation
  • 92.

    FieldTPerkinsJHuangY. 5-Azacitidine for myelodysplasia before allogeneic hematopoietic cell transplantation. Bone Marrow Transplant2010;45:255260.

    • Search Google Scholar
    • Export Citation
  • 93.

    GerdsATGooleyTAEsteyEH. Pretransplantation therapy with azacitidine vs induction chemotherapy and posttransplantation outcome in patients with MDS. Biol Blood Marrow Transplant2012;18:12111218.

    • Search Google Scholar
    • Export Citation
  • 94.

    LubbertMBertzHRuterB. Non-intensive treatment with low-dose 5-aza-2’-deoxycytidine (DAC) prior to allogeneic blood SCT of older MDS/AML patients. Bone Marrow Transplant2009;44:585588.

    • Search Google Scholar
    • Export Citation
  • 95.

    SantiniVAlmeidaAGiagounidisA. Randomized phase III study of lenalidomide versus placebo in RBC transfusion-dependent patients with lower-risk non-del(5q) myelodysplastic syndromes and ineligible for or refractory to erythropoiesis-stimulating agents. J Clin Oncol2016;34:29882996.

    • Search Google Scholar
    • Export Citation
  • 96.

    FenauxPGiagounidisASelleslagD. A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with low-/intermediate-1-risk myelodysplastic syndromes with del5q. Blood2011;118:37653776.

    • Search Google Scholar
    • Export Citation
  • 97.

    DeegHJJiangPYHolmbergLA. Hematologic responses of patients with MDS to antithymocyte globulin plus etanercept correlate with improved flow scores of marrow cells. Leuk Res2004;28:11771180.

    • Search Google Scholar
    • Export Citation
  • 98.

    MolldremJJCaplesMMavroudisD. Antithymocyte globulin for patients with myelodysplastic syndrome. Br J Haematol1997;99:699705.

  • 99.

    GargRFaderlSGarcia-ManeroG. Phase II study of rabbit antithymocyte globulin, cyclosporine and granulocyte colony-stimulating factor in patients with aplastic anemia and myelodysplastic syndrome. Leukemia2009;23:12971302.

    • Search Google Scholar
    • Export Citation
  • 100.

    PasswegJRGiagounidisAASimcockM. Immunosuppressive therapy for patients with myelodysplastic syndrome: a prospective randomized multicenter phase III trial comparing antithymocyte globulin plus cyclosporine with best supportive care—SAKK 33/99. J Clin Oncol2011;29:303309.

    • Search Google Scholar
    • Export Citation
  • 101.

    DunnDETanawattanacharoenPBoccuniP. Paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure syndromes. Ann Intern Med1999;131:401408.

    • Search Google Scholar
    • Export Citation
  • 102.

    SaunthararajahYNakamuraRNamJM. HLA-DR15 (DR2) is overrepresented in myelodysplastic syndrome and aplastic anemia and predicts a response to immunosuppression in myelodysplastic syndrome. Blood2002;100:15701574.

    • Search Google Scholar
    • Export Citation
  • 103.

    SloandEMWuCOGreenbergP. Factors affecting response and survival in patients with myelodysplasia treated with immunosuppressive therapy. J Clin Oncol2008;26:25052511.

    • Search Google Scholar
    • Export Citation
  • 104.

    ScheinbergPNunezOWeinsteinB. Horse versus rabbit antithymocyte globulin in acquired aplastic anemia. N Engl J Med2011;365:430438.

  • 105.

    StadlerMGermingUKlicheKO. A prospective, randomised, phase II study of horse antithymocyte globulin vs rabbit antithymocyte globulin as immune-modulating therapy in patients with low-risk myelodysplastic syndromes. Leukemia2004;18:460465.

    • Search Google Scholar
    • Export Citation
  • 106.

    AlsultanAGoldenbergNAKaiserN. Tacrolimus as an alternative to cyclosporine in the maintenance phase of immunosuppressive therapy for severe aplastic anemia in children. Pediatr Blood Cancer2009;52:626630.

    • Search Google Scholar
    • Export Citation
  • 107.

    MacartneyCFreilichMOdameI. Complete response to tacrolimus in a child with severe aplastic anemia resistant to cyclosporin A. Pediatr Blood Cancer2009;52:525527.

    • Search Google Scholar
    • Export Citation
  • 108.

    JerezAClementeMJMakishimaH. STAT3 mutations indicate the presence of subclinical T-cell clones in a subset of aplastic anemia and myelodysplastic syndrome patients. Blood2013;122:24532459.

    • Search Google Scholar
    • Export Citation
  • 109.

    ListAKurtinSRoeDJ. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med2005;352:549557.

  • 110.

    NimerSD. Clinical management of myelodysplastic syndromes with interstitial deletion of chromosome 5q. J Clin Oncol2006;24:25762582.

    • Search Google Scholar
    • Export Citation
  • 111.

    GiagounidisAMuftiGJMittelmanM. Outcomes in RBC transfusion-dependent patients with low-/intermediate-1-risk myelodysplastic syndromes with isolated deletion 5q treated with lenalidomide: a subset analysis from the MDS-004 study. Eur J Haematol2014;93:429438.

    • Search Google Scholar
    • Export Citation
  • 112.

    KuendgenALausekerMListAF. Lenalidomide does not increase AML progression risk in RBC transfusion-dependent patients with low- or intermediate-1-risk MDS with del(5q): a comparative analysis. Leukemia2013;24:10721079.

    • Search Google Scholar
    • Export Citation
  • 113.

    RazaAReevesJAFeldmanEJ. Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1 risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood2008;111:8693.

    • Search Google Scholar
    • Export Citation
  • 114.

    TomaAKosmiderOChevretS. Lenalidomide with or without erythropoietin in transfusion-dependent erythropoiesis-stimulating agent-refractory lower-risk MDS without 5q deletion. Leukemia2016;30:897905.

    • Search Google Scholar
    • Export Citation
  • 115.

    TricotGBoogaertsMA. The role of aggressive chemotherapy in the treatment of the myelodysplastic syndromes. Br J Haematol1986;63:477483.

    • Search Google Scholar
    • Export Citation
  • 116.

    EsteyEHThallPFCortesJE. 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. Blood2001;98:35753583.

    • Search Google Scholar
    • Export Citation
  • 117.

    SonneveldPvan DongenJJHagemeijerA. High expression of the multidrug resistance P-glycoprotein in high-risk myelodysplasia is associated with immature phenotype. Leukemia1993;7:963969.

    • Search Google Scholar
    • Export Citation
  • 118.

    AdvaniRSabaHITallmanMS. Treatment of refractory and relapsed acute myelogenous leukemia with combination chemotherapy plus the multidrug resistance modulator PSC 833 (Valspodar). Blood1999;93:787795.

    • Search Google Scholar
    • Export Citation
  • 119.

    WattelESolaryEHecquetB. Quinine improves results of intensive chemotherapy (IC) in myelodysplastic syndromes (MDS) expressing P-glycoprotein (PGP). Updated results of a randomized study. Adv Exp Med Biol1999;457:3546.

    • Search Google Scholar
    • Export Citation
  • 120.

    GreenbergPLLeeSJAdvaniR. 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 Oncol2004;22:10781086.

    • Search Google Scholar
    • Export Citation
  • 121.

    AndersonJEAppelbaumFRFisherLD. Allogeneic bone marrow transplantation for 93 patients with myelodysplastic syndrome. Blood1993;82:677681.

    • Search Google Scholar
    • Export Citation
  • 122.

    De WitteTZwaanFHermansJ. 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 Haematol1990;74:151155.

    • Search Google Scholar
    • Export Citation
  • 123.

    DemuynckHVerhoefGEZacheeP. Treatment of patients with myelodysplastic syndromes with allogeneic bone marrow transplantation from genotypically HLA-identical sibling and alternative donors. Bone Marrow Transplant1996;17:745751.

    • Search Google Scholar
    • Export Citation
  • 124.

    JuradoMDeegHJStorerB. 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 Transplant2002;8:161169.

    • Search Google Scholar
    • Export Citation
  • 125.

    KerbauyDMChyouFGooleyT. Allogeneic hematopoietic cell transplantation for chronic myelomonocytic leukemia. Biol Blood Marrow Transplant2005;11:713720.

    • Search Google Scholar
    • Export Citation
  • 126.

    NevillTJFungHCShepherdJD. Cytogenetic abnormalities in primary myelodysplastic syndrome are highly predictive of outcome after allogeneic bone marrow transplantation. Blood1998;92:19101917.

    • Search Google Scholar
    • Export Citation
  • 127.

    ScottBLSandmaierBMStorerB. Myeloablative vs nonmyeloablative allogeneic transplantation for patients with myelodysplastic syndrome or acute myelogenous leukemia with multilineage dysplasia: a retrospective analysis. Leukemia2006;20:128135.

    • Search Google Scholar
    • Export Citation
  • 128.

    WallenHGooleyTADeegHJ. Ablative allogeneic hematopoietic cell transplantation in adults 60 years of age and older. J Clin Oncol2005;23:34393446.

    • Search Google Scholar
    • Export Citation
  • 129.

    FukumotoJSGreenbergPL. Management of patients with higher risk myelodysplastic syndromes. Crit Rev Oncol Hematol2005;56:179192.

  • 130.

    RevickiDABrandenburgNAMuusP. Health-related quality of life outcomes of lenalidomide in transfusion-dependent patients with low- or intermediate-1-risk myelodysplastic syndromes with a chromosome 5q deletion: results from a randomized clinical trial. Leuk Res2013;37:259265.

    • Search Google Scholar
    • Export Citation
  • 131.

    OlivaENLatagliataRLaganaC. Lenalidomide in International Prognostic Scoring System Low and Intermediate-1 risk myelodysplastic syndromes with del(5q): an Italian phase II trial of health-related quality of life, safety and efficacy. Leuk Lymphoma2013;54:24582465.

    • Search Google Scholar
    • Export Citation
  • 132.

    Hellstrom-LindbergE. Efficacy of erythropoietin in the myelodysplastic syndromes: a meta-analysis of 205 patients from 17 studies. Br J Haematol1995;89:6771.

    • Search Google Scholar
    • Export Citation
  • 133.

    NegrinRSSteinRDohertyK. Maintenance treatment of the anemia of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor and erythropoietin: evidence for in vivo synergy. Blood1996;87:40764081.

    • Search Google Scholar
    • Export Citation
  • 134.

    GreenbergP. The role of hemopoietic growth factors in the treatment of myelodysplastic syndromes. Int J Ped HemOnc1997;4:231238.

  • 135.

    CasadevallNDurieuxPDuboisS. Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial. Blood2004;104:321327.

    • Search Google Scholar
    • Export Citation
  • 136.

    Hellstrom-LindbergENegrinRSteinR. Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model. Br J Haematol1997;99:344351.

    • Search Google Scholar
    • Export Citation
  • 137.

    SpiritiMALatagliataRNiscolaP. Impact of a new dosing regimen of epoetin alfa on quality of life and anemia in patients with low-risk myelodysplastic syndrome. Ann Hematol2005;84:167176.

    • Search Google Scholar
    • Export Citation
  • 138.

    Hellstrom-LindbergEGulbrandsenNLindbergG. 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 Haematol2003;120:10371046.

    • Search Google Scholar
    • Export Citation
  • 139.

    FiliCMalagolaMFolloMY. Prospective phase II Study on 5-days azacitidine for treatment of symptomatic and/or erythropoietin unresponsive patients with low/INT-1-risk myelodysplastic syndromes. Clin Cancer Res2013;19:32973308.

    • Search Google Scholar
    • Export Citation
  • 140.

    PlatzbeckerUWongRSVermaA. Safety and tolerability of eltrombopag versus placebo for treatment of thrombocytopenia in patients with advanced myelodysplastic syndromes or acute myeloid leukaemia: a multicentre, randomised, placebo-controlled, double-blind, phase 1/2 trial. Lancet Haematol2015;2:e417426.

    • Search Google Scholar
    • Export Citation
  • 141.

    GiagounidisAMuftiGJFenauxP. Results of a randomized, double-blind study of romiplostim versus placebo in patients with low/intermediate-1-risk myelodysplastic syndrome and thrombocytopenia. Cancer2014;120:18381846.

    • Search Google Scholar
    • Export Citation
  • 142.

    AlyeaEPKimHTHoV. Comparative outcome of nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation for patients older than 50 years of age. Blood2005;105:18101814.

    • Search Google Scholar
    • Export Citation
  • 143.

    CutlerCSLeeSJGreenbergP. A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome. Blood2004;104:579585.

    • Search Google Scholar
    • Export Citation
  • 144.

    AlessandrinoEPDella PortaMGBacigalupoA. WHO classification and WPSS predict posttransplantation outcome in patients with myelodysplastic syndrome: a study from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Blood2008;112:895902.

    • Search Google Scholar
    • Export Citation
  • 145.

    LaportGGSandmaierBMStorerBE. Reduced-intensity conditioning followed by allogeneic hematopoietic cell transplantation for adult patients with myelodysplastic syndrome and myeloproliferative disorders. Biol Blood Marrow Transplant2008;14:246255.

    • Search Google Scholar
    • Export Citation
  • 146.

    McCluneBLWeisdorfDJPedersenTL. Effect of age on outcome of reduced-intensity hematopoietic cell transplantation for older patients with acute myeloid leukemia in first complete remission or with myelodysplastic syndrome. J Clin Oncol2010;28:18781887.

    • Search Google Scholar
    • Export Citation
  • 147.

    Kindwall-KellerTIsolaLM. The evolution of hematopoietic SCT in myelodysplastic syndrome. Bone Marrow Transplant2009;43:597609.

  • 148.

    OlianskyDMAntinJHBennettJM. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of myelodysplastic syndromes: an evidence-based review. Biol Blood Marrow Transplant2009;15:137172.

    • Search Google Scholar
    • Export Citation
  • 149.

    DeegHSandmaierBM. Who is fit for allogeneic transplantation?Blood2010;116:47624770.

  • 150.

    SorrorMLSandmaierBMStorerBE. Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies. JAMA2011;306:18741883.

    • Search Google Scholar
    • Export Citation
  • 151.

    KrogerN. Allogeneic stem cell transplantation for elderly patients with myelodysplastic syndrome. Blood2012;119:56325639.

  • 152.

    BokhariSWWatsonLNagraS. Role of HCT-comorbidity index, age and disease status at transplantation in predicting survival and non-relapse mortality in patients with myelodysplasia and leukemia undergoing reduced-intensity-conditioning hemopoeitic progenitor cell transplantation. Bone Marrow Transplant2012;47:528534.

    • Search Google Scholar
    • Export Citation
  • 153.

    KorethJPidalaJPerezWS. Role of reduced-intensity conditioning allogeneic hematopoietic stem-cell transplantation in older patients with de novo myelodysplastic syndromes: an international collaborative decision analysis. J Clin Oncol2013;31:26622670.

    • Search Google Scholar
    • Export Citation
  • 154.

    BeranMShenYKantarjianH. High-dose chemotherapy in high-risk myelodysplastic syndrome: covariate-adjusted comparison of five regimens. Cancer2001;92:19992015.

    • Search Google Scholar
    • Export Citation
  • 155.

    GoreSDFenauxPSantiniV. A multivariate analysis of the relationship between response and survival among patients with higher-risk myelodysplastic syndromes treated within azacitidine or conventional care regimens in the randomized AZA-001 trial. Haematologica2013;98:10671072.

    • Search Google Scholar
    • Export Citation
  • 156.

    SeymourJFFenauxPSilvermanLR. Effects of azacitidine compared with conventional care regimens in elderly (>/= 75 years) patients with higher-risk myelodysplastic syndromes. Crit Rev Oncol Hematol2010;76:218227.

    • Search Google Scholar
    • Export Citation
  • 157.

    KornblithABHerndonJEIISilvermanLR. 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 Oncol2002;20:24412452.

    • Search Google Scholar
    • Export Citation
  • 158.

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

    • Search Google Scholar
    • Export Citation
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