Compassionate Use of Deferiprone for Patients With Thalassemia and Iron-Induced Heart Disease

Repeated red cell transfusions lead to transfusional iron overload because the body lacks an efficient mechanism to excrete excess iron. Without treatment, iron accumulates in the liver, heart and endocrine glands. Cardiac complications including arrhythmias and congestive heart failure are the most common cause of death from transfusional iron overload. New magnetic resonance imaging (MRI) T2* techniques enable an estimation of cardiac iron loading, and allow patients at the highest risk of cardiac disease (those with T2* < 10 ms) to be identified. For over 30 years, deferoxamine has been the standard therapy. However, the mode of administration is cumbersome (subcutaneous or intravenous infusion over 8 to 12 hours daily), leading to poor compliance. Thus, cardiac disease and early mortality continue to be a significant problem in patients treated with chronic transfusions. Treatment of cardiac complications involves intensifying therapy with deferoxamine, including recommending intravenous administration over a period of 24 hours daily. Deferiprone is an oral chelating agent, not FDA approved for use in the United States. Recent studies indicate that deferiprone is superior to deferoxamine in removing cardiac iron and reducing iron-induced cardiotoxicity. The most serious side effect of deferiprone is agranulocytosis, and other side effects are gastrointestinal symptoms, reversible arthralgia, reddish discoloration of urine and rare cases of autoimmune disease. Patients on the study will be closely monitored for these toxicities. Patients who are currently regularly followed at The Children's Hospital of Philadelphia will be prescribed deferiprone at 75 mg/kg/day in three divided doses, taken orally, in combination with deferoxamine, at the patient's current dose. Labs will be drawn once per week to monitor neutrophil count, with additional labs every three months to monitor ferritin and ALT levels.