A New Era in Iron Chelation Therapy: The Design of Optimal, Individually Adjusted Iron Chelation Therapies for the Complete Removal of Iron Overload in Thalassemia and other Chronically Transfused Patients

Abstract

A new era in iron chelation therapy began with the successful removal of excess iron load and the maintenance of normal iron stores in thalassemia patients using the International Committee on Chelation (ICOC) protocols. This achievement was based on two phases, firstly the introduction of deferiprone (L1) (80–100 mg/kg/day) and deferoxamine (DFO) (40–60 mg/kg at least 3 days per week) combination therapy, which appears to progressively remove all excess storage iron and thereafter by the introduction of L1 monotherapy that can maintain physiological range levels of serum ferritin, cardiac and liver magnetic resonance imaging (MRI) T2*. This new development is likely to change current practices and set a new gold standard in the treatment of transfusional iron loaded patients leading to an increased survival and the change of thalassemia from a fatal to a chronic disease. A major aspect of the improved therapies is the ability of L1 to mobilize and remove excess cardiac iron and reduce congestive cardiac failure, which is the main cause of death in thalassemia patients. Further, new developments include the use of alternating sequential chelation therapies and selected dose protocols with L1, DFO and deferasirox (DFRA) for overcoming toxicity and efficacy complications observed in some patients treated with monotherapies or combination therapies. The selection and adjustment of dose protocols is crucial for providing optimum chelation therapy for each individual patient.