JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
REVIEW
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Concepts and goals in the management of transfusional iron overload.

In this review, current concepts and goals of iron chelation therapy for thalassemias, sickle cell disease, and myelodysplastic syndromes are discussed. The primary goal of iron chelation therapy is to prevent the accumulation of iron reaching harmful levels by matching iron intake from blood transfusion, with iron excreted by iron chelation. Over 30 years of experience with deferoxamine has shown iron chelation to be an effective therapeutic modality. However, chelation efficiency is limited because most of the body's iron stores are not directly chelatable, and only a small fraction of body iron is chelatable at any moment. Once iron has been deposited in organs other than the liver, for example the heart, removal by chelation is slow and inefficient. Chelation efficiency can be improved by designing regimes where chelators are available 24 hr a day to bind labile iron pools in cells and plasma. Deferoxamine has a short plasma half-life and the parenteral infusions required to achieve steady plasma levels are demanding, with consequent variable adherence to therapy. Once-daily oral administration of deferasirox achieves continuous chelation with trough concentrations sufficient to decrease plasma labile iron species progressively, and achieves an efficiency of chelation not obtainable with deferiprone or deferoxamine monotherapy.

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