Orally active iron chelators

In patients with transfusion-dependent anemias, iron accumulation is fatal in the absence of chelating therapy. Extended survival, free of most complications of iron overload is observed in patients treated with early, adequate parenteral deferoxamine. Despite its success in prevention and treatment of iron toxicity, the expense and inconvenience of this therapy have stimulated a continued quest for an effective chelating agent that is orally active. Unfortunately, studies emerging over the last five years have confirmed that the most widely administered orally active agent, deferiprone (L1; 1,2-dimethyl-3-hydropyrid-4-one) may be harmfully ineffective in many patients: 18-65% of patients in six studies which obtained hepatic irons after long term deferiprone treatment had body iron exceeding the threshold for cardiac disease and premature death. The impact of deferiprone on cardiac and liver disease must be evaluated further, while the association between deferiprone and accelerated hepatic fibrosis still awaits refutation in large prospective trials. In view of the striking therapeutic successes of deferoxamine over the past 20 years, administration of deferiprone outside the setting of prospective clinical trials may need to be reconsidered. Meanwhile, an orally active iron chelator of demonstrated safety and effectiveness remains an objective for development for transfused patients.