Seminars in Hematology
Volume 44 , Pages S7-S11 , April 2007

Iron Chelation Therapy in the Context of the Latest Iron Science

  • Antonis Kattamis

      Affiliations

    • Corresponding Author InformationAddress correspondence to Professor Antonis Kattamis, MD, First Department of Pediatrics, University of Athens, Aghia Sophia Children’s Hospital, Thivon and Levadias, Goudi 115 27, Athens, Greece.

References 

  1. Andrews NC. Disorders of iron metabolism. N Engl J Med. 1999;341:1986–1995
  2. Kushner JP, Porter JP, Olivieri NF. Secondary iron overload. Hematology (Am Soc Hematol Educ Program). 2001;47–61
  3. Kattamis C, Kilinc Y, Fattoum S. Deferasirox (Exjade®, ICL670) demonstrates iron chelating efficacy related to transfusional iron intake in pediatric patients. Blood. 2005;106(11):2692;abstr
  4. Nick H, Acklin P, Lattmann R, et al. Development of tridentate iron chelators: From desferrithiocin to ICL670. Curr Med Chem. 2003;10:1065–1076
  5. 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
  6. Moeschlin S, Schnider U. Treatment of primary and secondary hemochromatosis and acute iron poisoning with a new, potent iron eliminating agent (desferrioxamine-B). N Engl J Med. 1963;269:57–66
  7. Cappellini MD. Overcoming the challenge of patient compliance with iron chelation therapy. Semin Hematol. 2005;42(suppl):S19–S21
  8. Treadwell M, Sung J, Murray E, et al. Barriers to deferoxamine adherence for adults with sickle cell disease. Blood. 2004;104(11):3670;abstr
  9. Ferripox. Summary of Product Characteristics. Ontario, Canada: Apotex, Toronto; 1999;
  10. Hider RC. Design of therapeutic chelating agents. Biochem Soc Trans. 2002;30:751–754
  11. al Refaie FN, Wonke B, Wickens DG, et al. Zinc concentration in patients with iron overload receiving oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one or desferrioxamine. J Clin Pathol. 1994;47:657–660
  12. Cohen AR, Galanello R, Piga A, et al. Safety profile of the oral iron chelator deferiprone: A multicentre study. Br J Haematol. 2000;108:305–312
  13. Desferal. Prescribing information. Basel, Switzerland: Novartis; 2002;
  14. Steinhauser S, Heinz U, Bartholoma M, et al. Complex formation of ICL670 and related ligands with Fe III and Fe II. Eur J Inorg Chem. 2004;21:4177–4192
  15. Porter J, Borgna-Pignatti C, Baccarani M, et al. Iron chelation efficiency of deferasirox (Exjade®, ICL670) in patients with transfusional hemosiderosis. Blood. 2005;106(11):2690;abstr
  16. Hoffbrand AV, Cohen A, Hershko C. Role of deferiprone in chelation therapy for transfusional iron overload. Blood. 2003;10217–10224
  17. 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
  18. Cabantchik ZI, Breuer W, Zanninelli G, et al. LPI-labile plasma iron in iron overload. Best Pract Res Clin Haematol. 2005;18:277–287
  19. Porter J. Pathophysiology of iron overload. Hematol Oncol Clin North Am. 2005;19(suppl 1):7–12
  20. Cunningham MJ, Nathan DG. New developments in iron chelators. Curr Opin Hematol. 2005;12:129–134
  21. Daar S, Taher A, Pathare A, et al. Deferasirox (Exjade®, ICL 670) provides 24-hour protection from labile plasma iron (LPI), in iron overloaded β-thalassaemia patients previously chelated with mono- or combination therapy. Haematologica. 2006;91(suppl 1):31;abstr
  22. Glickstein H, Ben El R, Shvartsman M, et al. Intracellular labile iron pools as direct targets of iron chelators (A fluorescence study of chelator action in living cells). Blood. 2005;106:3242–3250
  23. Cabantchik ZI, Link G, Glickstein H, et al. Deferasirox (Exjade®, ICL670): A journey into labile iron centers of living cardiomyocytes. Blood. 2005;106(11):824;abstr
  24. Wood JC, Otto-Duessel G, Gonzales H, et al. ICL670 removes cardiac iron in a gerbil model of iron overload. Blood. 2005;106:2695;(abstr)
  25. Cohen AR, Galanello R, Pennell DJ, et al. Thalassemia. Hematology (Am Soc Hematol Educ Program). 2004;14–34
  26. Liu ZD, Hider RC. Design of clinically useful iron(III)-selective chelators. Med Res Rev. 2002;22:26–64
  27. Cappellini MD, Cohen A, Piga A, et al. A phase III study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia. Blood. 2006;107:3455–3462
  28. 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
  29. Daar S, Pathare AV. Combined therapy with desferrioxamine and deferiprone in beta thalassemia major patients with transfusional iron overload. Ann Hematol. 2006;85:315–319
  30. Kattamis A, Ladis V, Berdousi H, et al. Iron chelation treatment with combined therapy with deferiprone and deferioxamine: A 12-month trial. Blood Cells Mol Dis. 2006;36:21–25
  31. Kattamis A. Combined therapy with deferoxamine and deferiprone. Ann N Y Acad Sci. 2005;1054:175–182
  32. Galanello R, Kattamis A, Piga A, et al. A prospective randomized controlled trial on the safety and efficacy of alternating deferoxamine and deferiprone in the treatment of iron overload in patients with thalassemia. Haematologica. 2006;91:1241–1243
  33. Cappellini MD, Vermylen C, Gathmann I, et al. Body iron balance and iron excretion:intake ratio, according to transfusional requirements, during treatment with the once-daily oral iron chelator deferasirox (Exjade, ICL670). Haematologica. 2006;91(suppl 1):16;abstr
  34. 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
  35. Piga A, Gaglioti C, Fogliacco E, et al. Comparative effects of deferiprone and deferoxamine on survival and cardiac disease in patients with thalassemia major: A retrospective analysis. Haematologica. 2003;88:489–496
  36. Olivieri NF, Nathan DG, MacMillan JH, et al. Survival in medically treated patients with homozygous β-thalassemia. N Engl J Med. 1994;331:574–578
  37. Anderson LJ, Wonke B, Prescott E, et al. Comparison of effects of oral deferiprone and subcutaneous desferrioxamine on myocardial iron concentrations and ventricular function in beta-thalassaemia. Lancet. 2002;360:516–520
  38. Pennell DJ, Berdoukas V, Karagiorga M, et al. Randomized controlled trial of deferiprone or deferoxamine in beta-thalassemia major patients with asymptomatic myocardial siderosis. Blood. 2006;107:3738–3744
  39. Ceci A, Baiardi P, Felisi M, et al. The safety and effectiveness of deferiprone in a large-scale, 3-year study in Italian patients. Br J Haematol. 2002;118:330–336
  40. Glickstein H, Ben El R, Link G, et al. Action of chelators in iron-loaded cardiac cells: accessibility to intracellular labile iron and functional consequences. Blood. 2006;108:3195–3203
  41. Porter JB, Tanner MA, Pennell DJ, et al. Improved myocardial T2* in transfusion dependent anemias receiving ICL670 (deferasirox). Blood. 2005;106(11):3600;abstr
  42. Eleftheriou P, Tanner M, Pennell D, et al. Response of myocardial T2* to oral deferasirox monotherapy for 1 year in 29 patients with transfusion-dependent anaemias; a subgroup analysis. Haematologica. 2006;91(suppl 1):999;abstr
  43. Cunningham MJ, Macklin EA, Neufeld EJ, et al. Complications of β-thalassemia major in North America. Blood. 2004;104:34–39
  44. al Refaie FN, Hershko C, Hoffbrand AV, et al. Results of long-term deferiprone (L1) therapy: A report by the International Study Group on Oral Iron Chelators. Br J Haematol. 1995;91:224–229
  45. EMEA. Deferiprone Summary of Product Characteristics. 2006. http://www.emea.eu.int/humandocs/PDFs/EPAR/Ferriprox/H-236-PI-en.pdf
  46. Naithani R, Chandra J, Sharma S. Safety of oral iron chelator deferiprone in young thalassaemics. Eur J Haematol. 2005;74:217–220
  47. Cohen A, Martin M, Schwartz E. Response to long-term deferoxamine therapy in thalassemia. J Pediatr. 1981;99:689–694
  48. Forni GL, Piga A, Galanello R, et al. Growth and sexual development in pediatric patients treated over 48 weeks with ICL670, a once-daily oral iron chelator. Pediatr Blood Cancer. 2005;44(11):1106;abstr

PII: S0037-1963(07)00057-1

doi: 10.1053/j.seminhematol.2007.03.006

Seminars in Hematology
Volume 44 , Pages S7-S11 , April 2007