Iron chelation therapy

Abstract

In chronic anemias associated with iron overload, iron chelation therapy is the only method available for preventing early death caused mainly by myocardial and hepatic iron toxicity. Although desferrioxamine (DFO) has been available for the treatment of transfusional iron overload since the early 1960s, the era of modern and effective iron chelation therapy started only 20 years ago with the introduction of subcutaneous DFO infusions by portable pumps. Today, long‐term DFO therapy is an integral part of the management of thalassemia and other transfusion‐dependent anemias, with a major impact on well‐being and survival. However, the high cost and rigorous requirements of DFO therapy and the significant toxicity of deferiprone underline the need for the continued development of new and improved orally effective iron chelators. In recent years, more than 1000 candidate compounds have been screened in animal models. These efforts have led to the identification of several interesting compounds, a few of which may be of possible clinical usefulness. The present review covers some of the most outstanding of these compounds, including deferiprone (L1), pyridoxal isonicotinoyl hydrazone (PIH), the polyanionic amines, the substituted polyaza compounds and bishydroxyphenyl tiazole. The introduction of these promising new chelators and the evolution of improved strategies of iron chelation therapy require a better understanding of the pathophysiology of iron toxicity and of the mechanisms of action of iron chelating drugs.