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Treatment of iron overload in hematological diseases (hereditary hemochromatosis excluded) Volume 12, issue 3, Juin 2006

Authors
Service d’hématologie biologique, AP-HP, hôpital Tenon, 4 rue de la Chine, 75970 Paris Cedex 20, Hôpital de jour de médecine, Service de radiologie, Service de médecine interne, hôpital Tenon, Paris

Iron overload occurs in two categories of hematological diseases. 1) Hematological diseases inducing a spontaneous intestinal iron hyperabsorption, which can be treated through phlebotomies; 2) hematological diseases treated with regular transfusions of red blood cells, which require iron-chelating therapy. The main organs affected by iron overload are the heart, the liver, some endocrine glands (hypophysis, gonads, thyroid, parathyroid, endocrine pancreas) and bones. The evaluation of iron storage may be done through direct methods: measurement of liver iron concentration by means of liver biopsies, imaging techniques (SQUID method, RMN techniques). Indirect methods are used in routine medical practise: measurement of serum iron levels, transferrine saturation, and, overall, serum ferritin levels. Over the last forty years, the iron chelating treatment mainly used deferoxamine (Desféral ®) with a dosage of 20-50 mg/kg body weight/day. The efficiency of this treatment was demonstrated thanks to a decreased mortality rate and morbidity for patients submitted to regular blood transfusion of red blood cells. The toxicity of deferoxamine is low. However, the parenteral mode of administration is not well tolerated and 20 to 40 % of patients become bad compliant in the long term. Deferiprone (Ferriprox ®, Kelfer ®) is a drug given per os at a dosage of 75 mg/kg body weight/day, three times a day. In patients treated with deferiprone iron overload may decrease, increase or stay equal. Deferiprone seems to have a better protective effect against iron overload in the heart than deferoxamine. The main complications of deferiprone are neutropenia and arthralgias. Over the last five years, many clinicians treated their patients with both deferoxamine and deferiprone. Deferasirox (Exjade ®) is an iron-chelating agent which is active per os. Several phase III trials including more than 1 000 patients were reported in December 2005. These reports showed deferasirox as having a global efficiency in reducing iron liver concentration and serum ferritin in patients receiving 25-30 mg/kg body weight/day during one year. This efficiency was non-inferior to that of deferoxamine given at the dosage 50 mg/kg body weight/day. An improvement of cardiac and/or hepatic anomalies preexisting to the treatment was observed in the patients at the end of the trial. The compliance to the treatment by deferasirox revealed to be highly better than that to treatment by deferoxamine. In the next future, deferasirox will be largely used in children and in adults to treat post transfusional iron overload. The expected issue of these on going long-term studies is the demonstration of a non-inferior effect of deferasirox versus deferoxamine regarding morbidity and mortality in patients regularly transfused with red blood cells.