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.