Blood Reviews
Volume 23 , Pages S15-S19 , December 2009

Impact of iron overload in myelodysplastic syndromes

  • Pierre Fenaux

      Affiliations

    • Groupe Francophone des Myélodysplasies (GFM), France
    • Avicenne Hospital and Paris 13 University, Paris, France
    • Corresponding Author InformationCorresponding author. Pierre Fenaux, MD, PhD. Hopital Avicenne – Service d'hématologie Clinique, 125 rue de Stalingrad, 93009 Bobigny, France
    • ,
  • Christian Rose

      Affiliations

    • Groupe Francophone des Myélodysplasies (GFM), France
    • St Vincent de Paul Hospital, Catholic University of Lille, Lille, France

References 

  1. Aul C , Giagounidis A , Germing U . Epidemiological features of myelodysplastic syndromes: results from regional cancer surveys and hospital-based statistics . Int J Hematol . 2001;73:405–410
  2. Ma X , Does M , Raza A , Mayne ST . Myelodysplastic syndromes: incidence and survival in the United States . Cancer . 2007;109:1536–1542
  3. Malcovati L , Della Porta MG , Laarakkers CM , et al.   Erythroid activity, transfusion iron overload, and hepcidin levels in patient with myelodysplastic syndrome . Blood . 2008;112: abstract 2676.
  4. Park S , Grabar S , Kelaidi C , et al.   Predictive factors of response and survival in myelodysplastic syndrome treated with erythropoietin and G-CSF: the GFM experience . Blood . 2008;111:574–582
  5. Porter JB . Practical management of iron overload . Br J Haematol . 2001;115:239–252
  6. Sanz GF , Sanz MA , Vellespí T , et al.   Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes: a multivariate analysis of prognostic factors in 370 patients . Blood . 1989;74:395–408
  7. Kelaidi C, Stamatoullas A, Beyne-Rauzy O, et al. Myelodysplastic syndrome (MDS) in France: results of a one-week cross-sectional survey on daily practice management in 919 patients by the GFM. Haematologica 2009; in press.
  8. Malcovati L , Porta MG , Pascutto C , et al.   Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making . J Clin Oncol . 2005;23:7594–7603
  9. Grootveld M , Bell JD , Halliwell B , et al.   Non-transferrin-bound iron in plasma or serum from patients with idiopathic haemochromatosis. Characterization by high performance liquid chromatography and nuclear magnetic resonance spectroscopy . J Biol Chem . 1989;264:4417–4422
  10. Breuer W , Greenberg E , Cabantchik ZI . Newly delivered transferrin iron and oxidative cell injury . FEBS Lett . 1997;403:213–219
  11. Au WY , Lam WWM , Chu WWC , et al.   A pilot MRI study of organ specific hemosiderosis and functional correlation in Chinese patients with myelodyplasia and aplastic anemia with raised ferritin levels . Hematol Oncol . 2008;26:225–228
  12. Chacko J , Pennell DJ , Tanner MA , et al.   Myocardial iron loading by magnetic resonance imaging T2* in good prognostic myelodysplastic syndrome patients on long-term blood transfusions . Br J Haematol . 2007;138:587–593
  13. Lu JP , Havashi K . Selective iron deposition in pancreatic islet B cells of transfusional iron-overloaded autopsy cases . Pathol Int . 1994;44:194–199
  14. Konen E , Ghoti H , Goitein O , et al.   No evidence for myocardial iron overload in multitransfused patients with myelodysplastic syndrome using cardiac magnetic resonance T2* technique . Am J Hematol . 2007;82:1013–1016
  15. Di Tucci AA , Matta G , Deplano S , et al.   Myocardial iron overload assessment by T2* magnetic resonance imaging in adult transfusion dependent patients with acquired anemias . Haematologica . 2008;93:1385–1388
  16. Buja LM , Roberts WC . Iron in the heart. Etiology and clinical significance . Am J Med . 1971;51:209–221
  17. Jensen PD , Jensen FT , Christensen T , et al.   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;101:4632–4639
  18. Cortelezzi A , Cattaneo C , Cristiani S , et al.   Non-transferrin-bound iron in myelodysplastic syndromes: a marker of ineffective erythropoiesis? . Hematol J . 2000;1:153–158
  19. Nemeth E . Iron regulation and erythropoiesis . Curr Opin Hematol . 2008;15:169–175
  20. Huang H , Constante M , Layoun A , Santos MM . Contribution of STAT3 and SMAD4 pathways to the regulation of hepcidin by opposing stimuli . Blood . 2009;113:3593–3599
  21. Tamary H , Shalev H , Perez-Avraham G , et al.   Elevated growth differentiation factor 15 expression in patients with congenital dyserythropoietic anemia type I . Blood . 2008;112:5241–5244
  22. Tanno T , Porayette P , Sripichai O , et al.   Identification of TWSG1 as a second novel erythroid regulator of hepcidin expression in murine and human cells . Blood . 2009;114:181–186
  23. Truksa J , Lee P , Beutler E . Two BMP responsive elements, STAT, and bZIP/HNF4/COUP motifs of the hepcidin promoter are critical for BMP, SMAD1, and HJV responsiveness . Blood . 2009;113:688–695
  24. Nearman ZP , Szpurka H , Serio B , et al.   Hemochromatosis-associated gene mutations in patients with myelodysplastic syndromes with refractory anemia with ringed sideroblasts . Am J Hematol . 2007;82:1076–1079
  25. Cazzola M , Barosi G , Gobbi PG , et al.   Natural history of idiopathic refractory sideroblastic anemia . Blood . 1988;71:305–312
  26. Schafer AI , Cheron RG , Dluhy R , et al.   Clinical consequences of acquired transfusional iron overload in adults . N Engl J Med . 1981;304:319–324
  27. Schafer AI , Cheron RG , Dluhy R , et al.   Clinical consequences of acquired sideroblastic anemia . Blood . 1988;71:305–312
  28. Malcovati L , Della Porta MG , Cazzola M . Predicting survival and leukemic evolution in patients with myelodysplastic syndrome . Haematologica . 2006;91:1588–1590
  29. Sanz G , Nomdedeu B , Such E , et al.   Independent impact of iron overload and transfusion dependency on survival and leukemic evolution in patients with myelodysplastic syndrome . Blood . 2008;112: abstract 640.
  30. Chee CE , Steensma DP , Wu W , et al.   Neither serum ferritin nor the number of red blood cell transfusions affect overall survival in refractory anemia with ringed sideroblasts . Am J Hematol . 2008;83:611–613
  31. Bennett JM . Consensus statement on iron overload in myelodysplastic syndromes . Am J Hematol . 2008;83:858–861
  32. Pullarkat V . Objectives of iron chelation therapy in myelodysplastic syndromes: more than meet the eye? . Blood . 2009; [Epub ahead of print].
  33. Takatoku M , Uchiyama T , Okamoto S , et al.   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 Hematol . 2007;78:487–494
  34. Goldberg SL , Mody-Patel N , Chen ER . Clinical and economic consequences of myelodysplastic syndromes in the United States: an analysis of the Medicare database . Blood . 2008;112: abstract 636.
  35. Asmis TR , Ding K , Seymour L , et al.   Age and comorbidity as independent prognostic factors in the treatment of non small-cell lung cancer: a review of National Cancer Institute of Canada Clinical Trials Group trials . J Clin Oncol . 2008;26:54–59
  36. Della Porta MG , Kuendgen A , Malcovati L , et al.   Myelodysplastic syndrome (MDS)-specific comorbidity index for predicting the impact of extra- hematological comorbidities on survival of patients with MDS . Blood . 2008;112: abstract 2677.
  37. Sorror M , Storer B , Sandmaier BM , et al.   Hematopoietic cell transplantationcomorbidity index and Karnofsky performance status are independent predictors of morbidity and mortality after allogeneic nonmyeloablative hematopoietic cell transplantation . Cancer . 2008;112:1992–2001
  38. Wood JC , Otto-Duessel M , Aguilar M , et al.   Cardiac iron determines cardiac T2*, T2, and T1 in the gerbil model of iron cardiomyopathy . Circulation . 2005;112:535–543
  39. Ferte C , Ernst O , Beyne-Rauzy O , et al.   Clinical relevance of cardiac iron overload estimated by MRI T2* in regularly transfused low risk MDS . Blood . 2006;108: abstract 2666.
  40. Ghoti H , Amer J , Winder A , et al.   Oxidative stress in red blood cells, platelets and polymorphonuclear leukocytes from patients with myelodysplastic syndrome . Eur J Haematol . 2007;79:463–467
  41. Leitch HA , Wong DHC , Leger CS , et al.   Improved leukemia-free and overall survival in patients with myelodysplastic syndrome receiving iron chelation therapy: a subgroup analysis . Blood . 2007;110: abstract 1469.
  42. Rose C , Brechignac S , Vassilief D , et al.   Positive impact of iron chelation therapy (CT) on survival in regularly transfused MDS patients. A prospective analysis by the GFM . Blood . 2007;110: abstract 249.
  43. Rose C, et al. Does iron chelation therapy improve survival in regularly transfused lower risk MDS patients? A multicenter study by the GFM. Leuk Res; in press.
  44. Armand P , Kim HT , Cutler CS , et al.   Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem cell transplantation . Blood . 2007;109:4586–4588
  45. Platzbecker U , Bornhäuser M , Germing U , et al.   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 Transplant . 2008;14:1217–1225
  46. Pullarkat V , Blanchard S , Tegtmeier B , et al.   Iron overload adversely affect outcome of allogeneic hematopoietic cell transplantation . Bone Marrow Transplant . 2008;42:799–805
  47. Rose C , Ernst O , Hecquet B , et al.   Quantification by magnetic resonance imaging and liver consequences of post-transfusional iron overload alone in long term survivors after allogeneic hematopoietic stem cell transplantation (HSCT) . Haematologica . 2007;92:850–853
  48. Sahlstedt L , Ebeling F , von Bonsdorff L , et al.   Non-transferrin-bound iron during allogeneic stem cell transplantation . Br J Haematol . 2001;113:836–838
  49. Dürken M , Nielsena P , Knobel S , et al.   Nontransferrin-bound iron in serum of patients receiving bone marrow transplants . Free Radic Biol Med . 1997;22:1159–1163
  50. Caroline L , Rosner F , Kozinn PJ . Elevated serum iron, low unbound transferrin and candidiasis in acute leukemia . Blood . 1969;34:441–451
  51. Karp JE , Merz WG . Association of reduced total iron binding capacity and fungal infections in leukemic granulocytic patients . J Clin Oncol . 1986;4:216–220
  52. von Bonsdorff L , Sahlstedt L , Ebeling F , et al.   Apotransferrin administration prevents growth of Staphylococcus epidermidis in serum of stem cell transplant patients by binding of free iron . FEMS Immunol Med Microbiol . 2003;37:45–51
  53. Boelaert JR , de Locht M , van Cutsem J , et al.   Mucormycosis during deferoxamine therapy is a siderophore mediated infection: in vitro and in vivo animal studies . J Clin Invest . 1993;91:1979–1986
  54. Ibrahim AS , Spellberg B , Edwards J . Iron acquisition: a novel perspective on mucormycosis pathogenesis and treatment . Curr Opin Infect Dis . 2008;21:620–625

PII: S0268-960X(09)70005-0

doi: 10.1016/S0268-960X(09)70005-0

Blood Reviews
Volume 23 , Pages S15-S19 , December 2009

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