The National Comprehensive Cancer Network (NCCN) convened a multidisciplinary task force to critically review the evidence for iron chelation and the rationale for treatment of transfusional iron overload in patients with myelodysplastic syndromes (MDS). The task force was charged with addressing issues related to tissue iron toxicity; the role of MRI in assessing iron overload; the rationale and role of treating transfusional iron overload in patients with MDS; and the impact of iron overload on bone marrow transplantation. This report summarizes the background data and ensuing discussion from the NCCN Task Force meeting on transfusional iron overload in MDS.

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  • 1

    GreenbergP. The role of hemopoietic growth factors in the treatment of myelodysplastic syndromes. Int J Ped Hem-Onc1997;4:231238.

  • 2

    GreenbergPAttarEBattiwallaM. NCCN Clinical Practice Guidelines in Oncology: Myelodysplastic Syndromes version 2.2010. Available at: Accessed December 11 2009.

  • 3

    ZurloMGDe StefanoPBorgna-PignattiC. Survival and causes of death in thalassaemia major. Lancet1989;2:2730.

  • 4

    HershkoCMLinkGMKonijnAMCabantchikZI. Iron chelation therapy. Curr Hematol Rep2005;4:110116.

  • 5

    OlivieriNFBrittenhamGM. Iron-chelating therapy and the treatment of thalassemia. Blood1997;89:739761.

  • 6

    MalcovatiL. Impact of transfusion dependency and secondary iron overload on the survival of patients with myelodysplastic syndromes. Leuk Res2007;31(Suppl 3):S26.

  • 7

    AndrewsNC. Iron homeostasis: insights from genetics and animal models. Nat Rev Genet2000;1:208217.

  • 8

    HershkoCLinkGCabantchikI. Pathophysiology of iron overload. Ann N Y Acad Sci1998;850:191201.

  • 9

    CortelezziACattaneoCCristianiS. Non-transferrin-bound iron in myelodysplastic syndromes: a marker of ineffective erythropoiesis?Hematol J2000;1:153158.

  • 10

    CabantchikZIBreuerWZanninelliGCianciulliP. LPI-labile plasma iron in iron overload. Best Pract Res Clin Haematol2005;18:277287.

  • 11

    EspositoBPBreuerWSirankaprachaP. Labile plasma iron in iron overload: redox activity and susceptibility to chelation. Blood2003;102:26702677.

  • 12

    NemethETuttleMSPowelsonJ. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science2004;306:20902093.

  • 13

    RiveraSLiuLNemethE. Hepcidin excess induces the sequestration of iron and exacerbates tumor-associated anemia. Blood2005;105:17971802.

  • 14

    GattermannN. Guidelines on iron chelation therapy in patients with myelodysplastic syndromes and transfusional iron overload. Leuk Res2007;31(Suppl 3):S1015.

  • 15

    WinderALefkowitzRGhotiH. Urinary hepcidin excretion in patients with myelodysplastic syndrome and myelofibrosis. Br J Haematol2008;142:669671.

  • 16

    OrigaRGalanelloRGanzT. Liver iron concentrations and urinary hepcidin in {beta}-thalassemia. Haematologica2007;92:583588.

  • 17

    PippardMJCallenderSTWarnerGTWeatherallDJ. Iron absorption and loading in beta-thalassaemia intermedia. Lancet1979;2:819821.

  • 18

    AndersonLJHoldenSDavisB. Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J2001;22:21712179.

  • 19

    WoodJCEnriquezCGhugreN. MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. Blood2005;106:14601465.

  • 20

    WoodJCOtto-DuesselMAguilarM. Cardiac iron determines cardiac T2*, T2, and T1 in the gerbil model of iron cardiomyopathy. Circulation2005;112:535543.

  • 21

    WoodJCEnriquezCGhugreN. Physiology and pathophysiology of iron cardiomyopathy in thalassemia. Ann N Y Acad Sci2005;1054:386395.

  • 22

    ChackoJPennellDJTannerMA. Myocardial iron loading by magnetic resonance imaging T2* in good prognostic myelodysplastic syndrome patients on long-term blood transfusions. Br J Haematol2007;138:587593.

  • 23

    Di TucciAAMattaGDeplanoS. Myocardial iron overload assessment by T2* magnetic resonance imaging in adult transfusion dependent patients with acquired anemias. Haematologica2008;93:13851388.

  • 24

    St PierreTGClarkPRChua-AnusornW. Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood2005;105:855861.

  • 25

    OlivieriNFNathanDGMacMillanJH. Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med1994;331:574578.

  • 26

    WoodJC. Cardiac iron across different transfusion-dependent diseases. Blood Rev2008;22(Suppl 2):1421.

  • 27

    ModellBKhanMDarlisonM. Improved survival of thalassaemia major in the UK and relation to T2* cardiovascular magnetic resonance. J Cardiovasc Magn Reson2008;10:42.

  • 28

    WangRGrossCPHaleneSMaX. Comorbidities and survival in a large cohort of patients with newly diagnosed myelodysplastic syndromes. Leuk Res2009;33:15941598.

  • 29

    BujaLMRobertsWC. Iron in the heart. Etiology and clinical significance. Am J Med1971;51:209221.

  • 30

    DeleaTEHagiwaraMPhatakPD. Retrospective study of the association between transfusion frequency and potential complications of iron overload in patients with myelodysplastic syndrome and other acquired hematopoietic disorders. Curr Med Res Opin2009;25:139147.

  • 31

    TakatokuMUchiyamaTOkamotoS. Retrospective nationwide survey of Japanese patients with transfusion-dependent MDS and aplastic anemia highlights the negative impact of iron overload on morbidity/mortality. Eur J Haematol2007;78:487494.

  • 32

    KaoJMMcMillanAGreenbergPL. International MDS risk analysis workshop (IMRAW)/IPSS reanalyzed: impact of cytopenias on clinical outcomes in myelodysplastic syndromes. Am J Hematol2008;83:765770.

  • 33

    KonenEGhotiHGoiteinO. No evidence for myocardial iron overload in multitransfused patients with myelodysplastic syndrome using cardiac magnetic resonance T2 technique. Am J Hematol2007;82:10131016.

  • 34

    ParkJOhyashikiKAkataS. Evaluation of cardiac iron overload in transfusion-dependent adult marrow failure patients by magnetic resonance imaging. Leuk Res2009;33:756758.

  • 35

    ArmandPKimHTCutlerCS. Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem cell transplantation. Blood2007;109:45864588.

  • 36

    PlatzbeckerUBornhauserMGermingU. Red blood cell transfusion dependence and outcome after allogeneic peripheral blood stem cell transplantation in patients with de novo myelodysplastic syndrome (MDS). Biol Blood Marrow Transplant2008;14:12171225.

  • 37

    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.

  • 38

    SchaferAICheronRGDluhyR. Clinical consequences of acquired transfusional iron overload in adults. N Engl J Med1981;304:319324.

  • 39

    JaegerMAulCSohngenD. Secondary hemochromatosis in polytransfused patients with myelodysplastic syndromes [in German]. Beitr Infusionsther1992;30:464468.

  • 40

    GoldbergSLMody-PatelNChenER. Clinical and economic consequences of myelodysplastic myndromes in the United States: an analysis of the medicare database [abstract]. Blood2008;112:Abstract 636.

  • 41

    CheeCESteensmaDPWuW. Neither serum ferritin nor the number of red blood cell transfusions affect overall survival in refractory anemia with ringed sideroblasts. Am J Hematol2008;83:611613.

  • 42

    SanzGNomdedeuBSuchE. Independent impact of iron overload and transfusion dependency on survival and leukemic evolution in patients with myelodysplastic syndrome [abstract]. Blood2008;112:Abstract 640.

  • 43

    LeitchHA. Improving clinical outcome in patients with myelodysplastic syndrome and iron overload using iron chelation therapy. Leuk Res2007;31(Suppl 3):S79.

  • 44

    JensenPDHeickendorffLPedersenB. The effect of iron chelation on haemopoiesis in MDS patients with transfusional iron overload. Br J Haematol1996;94:288299.

  • 45

    PorterJB. Practical management of iron overload. Br J Haematol2001;115:239252.

  • 46

    MaheshSGinzburgYVermaA. Iron overload in myelodysplastic syndromes. Leuk Lymphoma2008;49:427438.

  • 47

    ShashatyGFrankewichRChakrabortiT. Deferasirox for the treatment of chronic iron overload in transfusional hemosiderosis. Oncology (Williston Park)2006;20:179918061811.

  • 48

    GoldbergSL. Novel treatment options for transfusional iron overload in patients with myelodysplastic syndromes. Leuk Res2007;31(Suppl 3):S1622.

  • 49

    CappelliniMDBejaouiMAgaogluL. Prospective evaluation of patient-reported outcomes during treatment with deferasirox or deferoxamine for iron overload in patients with beta-thalassemia. Clin Ther2007;29:909917.

  • 50

    WimazalFNosslingerTBaumgartnerC. Deferasirox induces regression of iron overload in patients with myelodysplastic syndromes. Eur J Clin Invest2009;39:406411.

  • 51

    CappelliniMDEl-BeshlawyAKattamisA. Efficacy and safety of deferasirox (Exjade(R)) in patients with transfusion-dependent anemias: 1-year results from the large, prospective, multicenter EPIC study [abstract]. Blood2008;112:Abstract 3875.

  • 52

    PorterJBCappelliniMDEl-BeshlawyA. Effect of deferasirox (Exjade(R)) on labile plasma iron levels in heavily iron-overloaded patients with transfusion-dependent anemias enrolled in the large-scale, prospective 1-Year EPIC trial [abstract]. Blood2008;112:Abstract 3881.

  • 53

    GattermannNSchmidMPortaMD. Efficacy and safety of deferasirox (Exjade(R)) during 1 year of treatment in transfusion-dependent patients with myelodysplastic syndromes: results from EPIC trial [abstract]. Blood2008;112:Abstract 633.

  • 54

    ListAFBaerMRSteensmaD. Iron chelation with deferasirox (Exjade(R)) improves iron burden in patients with myelodysplastic syndromes (MDS) [abstract]. Blood2008;112:Abstract 634.

  • 55

    RachmilewitzEMerkelDGhotiH. Improvement of oxidative stress parameters in MDS patients with iron overload treated with deferasirox [abstract]. Blood2008;112:Abstract 2675.

  • 56

    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.

  • 57

    DeegHJShulmanHMAndersonJE. Allogeneic and syngeneic marrow transplantation for myelodysplastic syndrome in patients 55 to 66 years of age. Blood2000;95:11881194.

  • 58

    LucarelliGGalimbertiMPolchiP. Bone marrow transplantation in patients with thalassemia. N Engl J Med1990;322:417421.

  • 59

    KataokaKNannyaYHangaishiA. Influence of pretransplantation serum ferritin on nonrelapse mortality and nonmyeloablative allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant2009;15:195204.

  • 60

    AlessandrinoEPDella PortaMGBacigalupoA. Prognostic impact of pre-transplantation transfusion history and secondary iron overload in patients with myelodysplastic syndrome undergoing allogeneic stem cell transplantation: a study from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Haematologica2009; in press.

  • 61

    AltesARemachaAFSardaP. Frequent severe liver iron overload after stem cell transplantation and its possible association with invasive aspergillosis. Bone Marrow Transplant2004;34:505509.

  • 62

    StrasserSIKowdleyKVSaleGEMcDonaldGB. Iron overload in bone marrow transplant recipients. Bone Marrow Transplant1998;22:167173.

  • 63

    KambleRTSelbyGBMimsM. Iron overload manifesting as apparent exacerbation of hepatic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant2006;12:506510.

  • 64

    GreenbergPLCoslerLEFerroSALymanGH. The costs of drugs used to treat myelodysplastic syndromes following National Comprehensive Cancer Network Guidelines. J Natl Compr Canc Netw2008;6:942953.

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