Combined therapy with deferiprone and desferrioxamine in thalassemia major.

BACKGROUND AND OBJECTIVES Effective and convenient iron chelation remains one of the main targets of clinical management of thalassemia major. The combined treatment with desferrioxamine and deferiprone could have an increased chelation efficacy and sometimes allow drug doses and toxicity to be reduced and the number of days of desferrioxamine infusion to be decreased, improving compliance and quality of life. DESIGN AND METHODS We used combined therapy with desferrioxamine and deferiprone to treat 79 patients with severe iron overload (serum ferritin higher than 3000 ng/mL) who had low compliance with subcutaneous desferrioxamine. RESULTS Total therapy exposure was 201 patient-years. Three patients developed agranulocytosis and seven mild neutropenia. Other adverse effects were nausea, vomiting, abdominal pain, increased concentrations of liver transaminases and joint pain. The efficacy of combined therapy was evaluated in 64 patients treated for at least 12 months. Ferritin decreased from 5243+/-2345 to 3439+/-2446 ng/mL, p<0.001). Mean urinary iron excretion during combined therapy was double that with desferrioxamine or deferiprone monotherapy. In 20 patients receiving heart therapy at baseline, left ventricular ejection fraction increased from 48.6+/-9% to 57+/-6% (p=0.0001) over 12 to 57 months, without modifying the cardiac treatment. INTERPRETATION AND CONCLUSIONS Continuous deferiprone treatment with intermittent administration of subcutaneous desferrioxamine is a practical and effective procedure to decrease severe iron overload in patients with thalassemia major. This study also shows that the combined therapy is associated with an improvement in heart function.