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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
REVIEW
Chelation therapy in beta-thalassemia: an optimistic update.
Seminars in Hematology 2001 October
Iron chelation therapy with desferrioxamine (DFO) has dramatically improved the outlook in beta-thalassemia. Parenteral DFO reduces tissue iron stores, prevents iron-induced organ damage, and reduces morbidity and mortality, with little serious toxicity. However, the burden of prolonged subcutaneous portable pump infusions, high cost, and patient noncompliance have prompted the development of new methods of administration and new formulations of DFO as well as oral iron chelators. Deferiprone (L1), the only oral iron chelator studied in large long-term clinical trials, is less effective and more toxic than DFO and may not adequately control iron overload; however, compliance and quality of life are improved. Combinations of two iron chelators (such as parenteral DFO plus oral L1, or 2,3-DHB; or oral L1 plus HBED) have been shown to produce additive and synergistic effects, explained by the shuttle hypothesis. Iron bound to a "shuttle"--an oral agent that mobilizes tissue iron--is exchanged in the bloodstream with a "sink"--such as parenteral DFO--and excreted via the kidneys, while the shuttle is reutilized. Combination therapy may produce enhanced iron excretion, target specific iron compartments, minimize side effects, increase treatment options, improve compliance, and facilitate individualization of therapy. Better understanding of the kinetics of iron metabolism, iron overload, and chelation should improve therapeutic strategies.
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