Current Hematologic Malignancy Reports

, Volume 2, Issue 1, pp 13–21 | Cite as

Iron overload in patients with myelodysplastic syndromes

Article

Abstract

The myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell diseases characterized by ineffective hematopoiesis in one or more cell lines, resulting in insufficient bone marrow function. For most patients with MDS, supportive care by blood transfusions is still the mainstay of treatment. Especially in low-risk patients, anemia represents the major clinical problem, and many of these patients develop transfusional iron overload. This paper reviews the literature on transfusional iron overload in patients with MDS, looking at pathophysiology, evaluation, and treatment of the transfusional iron burden with desferrioxamine and oral chelators.

References and Recommended Reading

  1. 1.
    Bennett JM, Catovsky D, Daniel MT, et al.: Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982, 51:189–199.PubMedGoogle Scholar
  2. 2.
    Germing U, Gattermann N, Strupp C, et al.: Validation of the WHO proposals for a new classification of primary myelodysplastic syndromes: a retrospective analysis of 1600 patients. Leuk Res 2000, 24:983–992.PubMedCrossRefGoogle Scholar
  3. 3.
    Cazzola M, Anderson JE, Ganser A, Hellstrom-Lindberg E: A patient-oriented approach to treatment of myelodysplastic syndromes. Haematologica 1998, 83:910–935.PubMedGoogle Scholar
  4. 4.
    Pootrakul P, Kitcharoen K, Yansukon P, et al.: The effect of erythroid hyperplasia on iron balance. Blood 1988, 71:1124–1129.PubMedGoogle Scholar
  5. 5.
    Cazzola M, Barosi G, Gobbi PG: Natural history of idiopathic refractory sideroblastic anemia. Blood 1988, 71:305–312.PubMedGoogle Scholar
  6. 6.
    Hershko C, Rachmilewitz EA: Mechanism of desferrioxamine-induced iron excretion in thalassaemia. Br J Haematol 1979, 42:125–132.PubMedGoogle Scholar
  7. 7.
    Hershko C, Konijn AM, Link G: Iron chelators for thalassaemia. Br J Haematol 1998, 101:399–406.PubMedCrossRefGoogle Scholar
  8. 8.
    Esposito BP, Breuer W, Sirankapracha P, et al.: Labile plasma iron in iron overload: redox activity and susceptibility to chelation. Blood 2003, 102:2670–2677.PubMedCrossRefGoogle Scholar
  9. 9.
    Pootrakul P, Breuer W, Sametband M, et al.: Labile plasma iron (LPI) as an indicator of chelatable plasma redox activity in iron-overloaded beta-thalassemia/HbE patients treated with an oral chelator. Blood 2004, 104:1504–1510.PubMedCrossRefGoogle Scholar
  10. 10.
    Link G, Pinson A, Hershko C: Heart cells in culture: a model of myocardial iron overload and chelation. J. Lab Clin Med 1985, 106:147–153.PubMedGoogle Scholar
  11. 11.
    Randell EW, Parkes JG, Olivieri NF, Templeton DM: Uptake of non-transferrin-bound iron by both reductive and nonreductive processes is modulated by intracellular iron. J Biol Chem 1994, 269:16046–16053.PubMedGoogle Scholar
  12. 12.
    Gutteridge JM, Rowley DA, Griffiths E, Halliwell B: Low-molecular-weight iron complexes and oxygen radical reactions in idiopathic haemochromatosis. Clin Sci (Colch) 1985, 68:463–467.Google Scholar
  13. 13.
    Hershko C, Link G, Cabantchik I: Pathophysiology of iron overload. Ann N Y Acad Sci 1998, 850:191–201.PubMedCrossRefGoogle Scholar
  14. 14.
    Modell B, Berdoukas V: The Clinical Approach to Thalassemia. New York: Grune and Stratton; 1981.Google Scholar
  15. 15.
    Pippard M: Measurement of iron status. Prog Clin Biol Res 1989, 309:705–713.Google Scholar
  16. 16.
    Barry M: Liver iron concentration, stainable iron and total body storage iron. Gut 1974, 15:411–415.PubMedGoogle Scholar
  17. 17.
    Brissot P, Bourel M, Herry D, et al.: Assessment of liver iron content in 271 patients: a reevaluation of direct and indirect methods. Gastroenterology 1981, 80:557–565.PubMedGoogle Scholar
  18. 18.
    Angelucci E, Brittenham GM, McLaren CE, et al.: Hepatic iron concentration and total body iron stores in thalassemia major. N Engl J Med 2000, 343:327–331.PubMedCrossRefGoogle Scholar
  19. 19.
    Angelucci E, Baronciani D, Lucarelli G, et al.: Needle liver biopsy in thalassaemia: analyses of diagnostic accuracy and safety in 1184 consecutive biopsies. Br J Haematol 1995, 89:757–761.PubMedCrossRefGoogle Scholar
  20. 20.
    Brittenham GM, Badman DG: Noninvasive measurement of iron: report of an NIDDK workshop. Blood 2003, 101:15–19.PubMedCrossRefGoogle Scholar
  21. 21.
    St. Pierre TG, Clark PR, Chua-anusorn W, et al.: Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood 2005, 105:855–861.PubMedCrossRefGoogle Scholar
  22. 22.
    Clark PR, Chua-anusorn W, St. Pierre TG: Proton transverse relaxation rate (R2) images of iron-loaded liver tissue; mapping local tissue iron concentrations with MRI. Magn Reson Med 2003, 49:572–575. [Published erratum appears in Magn Reson Med 2003, 49:1201.]PubMedCrossRefGoogle Scholar
  23. 23.
    Wood JC, Enriquez C, Ghugre N, et al.: MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. Blood 2005, 106:1460–1465.PubMedCrossRefGoogle Scholar
  24. 24.
    Jensen PD, Jensen FT, Christensen T, Ellegaard J: Non-invasive assessment of tissue iron overload in the liver by magnetic resonance imaging. Br J Haematol 1994, 87:171–184.PubMedGoogle Scholar
  25. 25.
    Konijn AM: Iron metabolism in inflammation. Baillieres Clin Haematol 1994, 7:829–849.PubMedCrossRefGoogle Scholar
  26. 26.
    Tran TN, Eubanks SK, Schaffer KJ: Secretion of ferritin by rat hepatoma cells and its regulation by inflammatory cytokines and iron. Blood 1997, 90:4979–4986.PubMedGoogle Scholar
  27. 27.
    Prieto J, Barry M, Sherlock S: Serum ferritin in patients with iron overload and with acute and chronic liver diseases. Gastroenterology 1975, 68:525–533.PubMedGoogle Scholar
  28. 28.
    Brittenham GM, Cohen AR, McLaren CE, et al.: Hepatic iron stores and plasma ferritin concentration in patients with sickle cell anemia and thalassemia major. Am J Hematol 1993, 42:81–85.PubMedCrossRefGoogle Scholar
  29. 29.
    Nielsen P, Fischer R, Engelhardt R, et al.: Liver iron stores in patients with secondary haemosiderosis under iron chelation therapy with deferoxamine or deferiprone. Br J Haematol 1995, 91:827–833.PubMedGoogle Scholar
  30. 30.
    Jensen PD, Jensen FT, Christensen T, Ellegaard J: Evaluation of transfusional iron overload before and during iron chelation by magnetic resonance imaging of the liver and determination of serum ferritin in adult non-thalassaemic patients. Br J Haematol 1995, 89:880–889.PubMedCrossRefGoogle Scholar
  31. 31.
    Jensen PD, Jensen FT, Christensen T, et al.: Relationship between hepatocellular injury and transfusional iron overload prior to and during iron chelation with desferrioxamine: a study in adult patients with acquired anemias. Blood 2003, 101:91–96.PubMedCrossRefGoogle Scholar
  32. 32.
    Jensen PD, Jensen FT, Christensen T, et al.: Indirect evidence for the potential ability of magnetic resonance imaging to evaluate the myocardial iron content in patients with transfusional iron overload. Magma 2001, 12:153–166.PubMedGoogle Scholar
  33. 33.
    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.PubMedCrossRefGoogle Scholar
  34. 34.
    Brittenham GM, Griffith PM, Nienhuis AW, et al.: Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N Engl J Med 1994, 331:567–573.PubMedCrossRefGoogle Scholar
  35. 35.
    Engle MA, Erlandson M, Smith CH: Late cardiac complications of chronic severe, refractory anaemia with hemochromatosis. Circulation 1964, 30:698–705.PubMedGoogle Scholar
  36. 36.
    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.PubMedCrossRefGoogle Scholar
  37. 37.
    Jaeger M, Aul C, Sohngen D, et al.: Secondary hemochromatosis in polytransfused patients with myelodysplastic syndromes] [German]. Beitr Infusionsther 1992, 30:464–468.PubMedGoogle Scholar
  38. 38.
    Cohen A, Martin M, Schwartz E: Depletion of excessive liver iron stores with desferrioxamine. Br J Haematol 1984, 58:369–373.PubMedGoogle Scholar
  39. 39.
    Freeman AP, Giles RW, Berdoukas VA, et al.: Sustained normalization of cardiac function by chelation therapy in thalassaemia major. Clin Lab Haematol 1989, 11:299–307.PubMedCrossRefGoogle Scholar
  40. 40.
    Wolfe L, Olivieri N, Sallan D, et al.: Prevention of cardiac disease by subcutaneous deferoxamine in patients with thalassemia major. N Engl J Med 1985, 312:1600–1603.PubMedCrossRefGoogle Scholar
  41. 41.
    De Sanctis V, Zurlo MG, Senesi E, et al.: Insulin dependent diabetes in thalassaemia. Arch Dis Child 1988, 63:58–62.PubMedGoogle Scholar
  42. 42.
    Bronspiegel-Weintrob N, Olivieri NF, Tyler B, et al.: Effect of age at the start of iron chelation therapy on gonadal function in beta-thalassemia major. N Engl J Med 1990, 323:713–719.PubMedCrossRefGoogle Scholar
  43. 43.
    Olivieri NF, Nathan DG, MacMillan JH, et al.: Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med 1994, 331:574–578.PubMedCrossRefGoogle Scholar
  44. 44.
    Olivieri NF, Brittenham GM: Iron-chelation therapy and the treatment of thalassemia. Blood 1997, 89:739–761.PubMedGoogle Scholar
  45. 45.
    Schafer AI, Rabinowe S, Le Boff MS, et al.: Long-term efficacy of deferoxamine iron chelation therapy in adults with acquired transfusional iron overload. Arch Intern Med 1985, 145:1217–1221.PubMedCrossRefGoogle Scholar
  46. 46.
    Di Gregorio F, Romeo MA, Pizzarelli G, et al.: An alternative to continuous subcutaneous infusion of desferrioxamine in thalassaemic patients. Br J Haematol 1997, 98:601–602.PubMedCrossRefGoogle Scholar
  47. 47.
    Borgna-Pignatti C, Franchini M, Gandini G, et al.: Subcutaneous bolus injection of deferoxamine in adult patients affected by onco-hematologic diseases and iron overload. Haematologica 1998, 83:788–790.PubMedGoogle Scholar
  48. 48.
    Franchini M, Gandini G, de Gironcoli M, et al.: Safety and efficacy of subcutaneous bolus injection of deferoxamine in adult patients with iron overload. Blood 2000, 95:2776–2779.PubMedGoogle Scholar
  49. 49.
    Jensen PD, Heickendorff L, Pedersen B, et al.: The effect of iron chelation on haemopoiesis in MDS patients with transfusional iron overload. Br J Haematol 1996, 94:288–299.PubMedCrossRefGoogle Scholar
  50. 50.
    Porter JB, Davis BA: Monitoring chelation therapy to achieve optimal outcome in the treatment of thalassaemia [review]. Best Pract Res Clin Haematol 2002, 15:329–368.PubMedGoogle Scholar
  51. 51.
    Haines ME, Wainscoat JS: Relapsing sideroblastic anaemia. Br J Haematol 1991, 78:285–286.PubMedGoogle Scholar
  52. 52.
    Del Rio Garma J, Fernandez Lago C, Batlle Fonrodona FJ: Desferrioxamine in the treatment of myelodysplastic syndromes. Haematologica 1997, 82:639–640.PubMedGoogle Scholar
  53. 53.
    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.PubMedCrossRefGoogle Scholar
  54. 54.
    Cohen AR, Galanello R, Piga A, et al: Safety and effectiveness of long-term therapy with the oral iron chelator deferiprone. Blood 2003, 102:1583–1587.PubMedCrossRefGoogle Scholar
  55. 55.
    Hoffbrand AV, Cohen A, Hershko C: Role of deferiprone in chelation therapy for transfusional iron overload. Blood 2003, 102:17–24.PubMedCrossRefGoogle Scholar
  56. 56.
    Wonke B, Wright C, Hoffbrand AV: Combined therapy with deferiprone and desferrioxamine. Br J Haematol 1998, 103:361–364.PubMedCrossRefGoogle Scholar
  57. 57.
    Anderson LJ, Wonke B, Prescott E, et al.: Comparison of effect of oral deferiprone and subcutaneous desferrioxamine on myocardial iron concentrations and ventricular function in beta-thalassaemia. Lancet 2002, 360:516–520.PubMedCrossRefGoogle Scholar
  58. 58.
    Borgna-Pignatti C, Cappellini MD, De Stefano P, et al.: Cardiac morbidity and mortality in deferoxamine-or deferiprone-treated patients with thalassemia major. Blood 2006, 107:3733–3737.PubMedCrossRefGoogle Scholar
  59. 59.
    Kersten MJ, Lange R, Smeets ME, et al.: Long-term treatment of transfusional iron overload with the oral iron chelator deferiprone (L1): a Dutch multicenter trial. Ann Hematol 1996, 73:247–252.PubMedCrossRefGoogle Scholar
  60. 60.
    Nisbet-Brown E, Olivieri NF, Giardina PJ, et al.: Effectiveness and safety of ICL670 in iron-loaded patients with thalassaemia: a randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet 2003, 361:1597–1602.PubMedCrossRefGoogle Scholar
  61. 61.
    Nick H, Wong A, Acklin P, et al.: ICL670A: preclinical profile. Adv Exp Med Biol 2002, 509:185–203.PubMedGoogle Scholar
  62. 62.
    Cappellini MD: Iron-chelating therapy with the new oral agent ICL670 (Exjade). Best Pract Res Clin Haematol 2005, 18:289–298.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2007

Authors and Affiliations

  1. 1.Department of HematologyÅrhus University Hospital, Aalborg HospitalAalborgDenmark

Personalised recommendations