Background-Cardiac complications secondary to iron overload are the leading cause of death in ␤-thalassemia major.Approximately two thirds of patients maintained on the parenteral iron chelator deferoxamine have myocardial iron loading. The oral iron chelator deferiprone has been demonstrated to remove myocardial iron, and it has been proposed that in combination with deferoxamine it may have additional effect. Methods and Results-Myocardial iron loading was assessed with the use of myocardial T2* cardiovascular magnetic resonance in 167 patients with thalassemia major receiving standard maintenance chelation monotherapy with subcutaneous deferoxamine. Of these patients, 65 with mild to moderate myocardial iron loading (T2* 8 to 20 ms) entered the trial with continuation of subcutaneous deferoxamine and were randomized to receive additional oral placebo (deferoxamine group) or oral deferiprone 75 mg/kg per day (combined group). The primary end point was the change in myocardial T2* over 12 months. Secondary end points of endothelial function (flow-mediated dilatation of the brachial artery) and cardiac function were also measured with cardiovascular magnetic resonance. There were significant improvements in the combined treatment group compared with the deferoxamine group in myocardial T2* (ratio of change in geometric means 1.50 versus 1.24; Pϭ0.02), absolute left ventricular ejection fraction (2.6% versus 0.6%; Pϭ0.05), and absolute endothelial function (8.8% versus 3.3%; Pϭ0.02). There was also a significantly greater improvement in serum ferritin in the combined group (Ϫ976 versus Ϫ233 g/L; PϽ0.001). Conclusions-In comparison to the standard chelation monotherapy of deferoxamine, combination treatment with additional deferiprone reduced myocardial iron and improved the ejection fraction and endothelial function in thalassemia major patients with mild to moderate cardiac iron loading.

Background: The UK Thalassaemia Register records births, deaths and selected clinical data of patients with thalassaemia who are resident in the UK. A study of survival and causes of death was undertaken which aimed to include the possible impact of T2* cardiovascular magnetic resonance (CMR).

Most deaths in beta-thalassemia major result from cardiac complications due to iron overload. Differential effects on myocardial siderosis may exist between different chelators. A randomized controlled trial was performed in 61 patients previously maintained on subcutaneous deferoxamine. The primary end point was the change in myocardial siderosis (myocardial T2*) over 1 year in patients maintained on subcutaneous deferoxamine or those switched to oral deferiprone monotherapy. The dose of deferiprone was 92 mg/kg/d and deferoxamine was 43 mg/kg for 5.7 d/wk. Compliance was 94% ؎ 5.3% and 93% ؎ 9.7% (P ‫؍‬ .81), respectively. The improvement in myocardial T2* was significantly greater for deferiprone than deferoxamine (27% vs 13%; P ‫؍‬ .023). Left ventricular ejection fraction increased significantly more in the deferipronetreated group (3.1% vs 0.3% absolute units; P ‫؍‬ .003). The changes in liver iron level (؊0.93 mg/g dry weight vs ؊1.54 mg/g dry weight; P ‫؍‬ .40) and serum ferritin level (؊181 g/L vs ؊466 g/L; P ‫؍‬ .16), respectively, were not significantly different between groups. The most frequent adverse events were transient gastrointestinal symptoms for deferipronetreated patients and local reactions at the infusion site for deferoxamine. There were no episodes of agranulocytosis. Deferiprone monotherapy was significantly more effective than deferoxamine over 1 year in improving asymptomatic myocardial siderosis in beta-thalassemia major. (Blood. 2006;107: 3738-3744)

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