Optimizing iron chelation strategies in beta-thalassaemia major. 2009

John B Porter
Department of Haematology, University College London, London, UK. j.porter@ucl.ac.uk

beta-thalassaemia has served as a paradigm for chelation management for over three decades, both in terms of defining the complications of transfusional iron overload, and demonstrating the benefits of chelation therapy. Iron chelation therapy can be used to reduce unacceptably high tissue iron levels, or to maintain current levels if these are deemed safe, by matching the rate of transfused iron. Chelation therapy should be tailored to the individual patient, based on the transfusional iron loading rate and the current level of iron load both intra- and extra-hepatically, for example in the myocardium. In general, it is preferable to prevent extra-hepatic complications by controlling the body iron load rather than attempting to rescue patients once extra-hepatic complications have developed. Deferoxamine, which has been available since the late 1970s and is given parenterally, has been shown to prolong life and decrease morbidity from iron overload in patients who comply with therapy. Deferiprone may control body iron as oral monotherapy in a variable proportion of patients but is now more frequently used in combinations with deferoxamine, either to control total levels of body iron or to reduce increased levels of myocardial iron. In this article, recent advances in the use of deferasirox, a once-daily oral iron chelator, are reviewed. Large-scale prospective trials show efficacy with an acceptable safety profile in adults and children with up to 5 years follow-up. Recent evidence suggests that deferasirox up to 30 mg/kg/day can be safely administered to patients with serum ferritin levels between 500 and 1000 mg/L, while doses above 30 mg/kg/day can be given to patients with substantial iron overload or with high transfusion rates. Further, prospective data show that myocardial iron can be effectively decreased with this chelation treatment.

UI MeSH Term Description Entries
D007501 Iron A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN. Iron-56,Iron 56
D007502 Iron Chelating Agents Organic chemicals that form two or more coordination links with an iron ion. Once coordination has occurred, the complex formed is called a chelate. The iron-binding porphyrin group of hemoglobin is an example of a metal chelate found in biological systems. Iron Chelates,Agents, Iron Chelating,Chelates, Iron,Chelating Agents, Iron
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D017086 beta-Thalassemia A disorder characterized by reduced synthesis of the beta chains of hemoglobin. There is retardation of hemoglobin A synthesis in the heterozygous form (thalassemia minor), which is asymptomatic, while in the homozygous form (thalassemia major, Cooley's anemia, Mediterranean anemia, erythroblastic anemia), which can result in severe complications and even death, hemoglobin A synthesis is absent. Anemia, Cooley's,Anemia, Erythroblastic,Anemia, Mediterranean,Hemoglobin F Disease,Thalassemia Major,Thalassemia Minor,Erythroblastic Anemia,Mediterranean Anemia,Microcytemia, beta Type,Thalassemia Intermedia,Thalassemia Major (beta-Thalassemia Major),Thalassemia Minor (beta-Thalassemia Minor),Thalassemia, beta Type,beta Thalassemia,Anemia, Cooley,Anemia, Cooleys,Anemias, Erythroblastic,Anemias, Mediterranean,Cooley's Anemia,Disease, Hemoglobin F,Intermedia, Thalassemia,Intermedias, Thalassemia,Major, Thalassemia (beta-Thalassemia Major),Majors, Thalassemia (beta-Thalassemia Major),Mediterranean Anemias,Microcytemias, beta Type,Minor, Thalassemia (beta-Thalassemia Minor),Minors, Thalassemia (beta-Thalassemia Minor),Thalassemia Intermedias,Thalassemia Major (beta Thalassemia Major),Thalassemia Majors (beta-Thalassemia Major),Thalassemia Minor (beta Thalassemia Minor),Thalassemia Minors (beta-Thalassemia Minor),Thalassemia, beta,Thalassemias, beta,Thalassemias, beta Type,Type Microcytemia, beta,Type Microcytemias, beta,Type Thalassemia, beta,Type Thalassemias, beta,beta Thalassemias,beta Type Microcytemia,beta Type Microcytemias,beta Type Thalassemia,beta Type Thalassemias
D019190 Iron Overload An excessive accumulation of iron in the body due to a greater than normal absorption of iron from the gastrointestinal tract or from parenteral injection. This may arise from idiopathic hemochromatosis, excessive iron intake, chronic alcoholism, certain types of refractory anemia, or transfusional hemosiderosis. (From Churchill's Illustrated Medical Dictionary, 1989) Overload, Iron

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