Combined therapy with desferrioxamine and deferiprone in beta thalassemia major patients with transfusional iron overload.

Iron overload is the main cause of morbidity and mortality especially from heart failure in patients with beta thalassemia major (TM). Successful iron chelation is therefore essential for the optimal management of TM. Although desferrioxamine (DFX) has been the major iron-chelating treatment of transfusional iron overload, compliance is a major hindrance in achieving optimal therapeutic results. The availability of oral iron chelation with deferiprone (L(1)) since 1987 is useful but showed poor efficacy when used alone as compared to DFX. We therefore decided to compare DFX alone with a prospective combined therapy with DFX and L(1) in beta thalassemia major patients with iron overload. We studied 91 patients with beta thalassemia major (mean age+/-SD, 15.02+/-5.8; range 2-30 years) attending the day care unit for regular transfusional support. They received packed red cells every 3-4 weeks to maintain pretransfusion hemoglobin concentration above 9 g/dl. They had been receiving DFX at a daily dose of 40 mg kg(-1) day(-1) by subcutaneous infusion for 8-10 h on 4-5 nights each week for the past several years. However, due to various reasons, they had developed considerable transfusional iron overload. These patients were allocated to prospectively receive additional therapy with oral iron chelator L(1) at 75 mg kg(-1) day(-1) body weight in three divided doses with food after informed consent and continued to receive treatment with DFX as per the above dosage. Of the 91 patients, six developed severe gastrointestinal (GI) upset, two agranulocytosis, two arthropathy, one persistently raised liver enzymes, two died owing to sepsis, and two received allogeneic bone marrow transplantation. Amongst the remaining 76 patients, 21 were found noncompliant (not taking DFX regularly, but taking L(1) regularly). Thus, in the 55 evaluable patients {6-48 months on combination therapy; mean [(+/-SD)22+/-12 months]}, the mean serum ferritin (+/-SD) fell dramatically from 3,088 (+/-1,299) ng/ml (DFX alone) to 2,051 (+/-935) ng/ml (DFX and L(1); p<0.001). It is interesting to note that there was also a significant improvement in the myocardial function as assessed by the ejection fraction (p<0.004) and fractional shortening (p<0.05) in those patients (n=42) who could be studied after being on combination therapy for a minimum of 1 year. The study emphasizes that beta thalassemia major patients with transfusional iron overload can be successfully treated with a combination of DFX and L(1). Our results also demonstrate a significant statistical improvement after as little as 6 months of combination therapy. Furthermore, these improvements lead to a progressive fall in the mean serum ferritin. Lastly, the study also demonstrates significant improvement in the echocardiographic parameters of myocardial performance in these patients receiving combination therapy.