IRON CHELATION BY DEFEROXAMINE IN SICKLE-CELL PATIENTS WITH SEVERE TRANSFUSION-INDUCED HEMOSIDEROSIS - A RANDOMIZED, DOUBLE-BLIND-STUDY OF THE DOSE-RESPONSE RELATIONSHIP

Transfusion-induced hemosiderosis is a serious and potentially life-th reatening complication for some patients with sickle cell anemia. The use of high-dose intravenous deferoxamine (DFO) has become widespread in spite of a paucity of published data on safety and efficacy. We rep ort a randomized double-blind study of the dose-response relationship of intravenous DFO in six subjects with sickle cell anemia and severe transfusion-induced hemosiderosis (serum ferritin 4100 to 14,176 ng/ml ). Each subject received three different doses of intravenous DFO for 3 days each while consuming a constant diet. Total iron excretion (uri ne and fecal) was 91% greater at 180 mg/kg/day DFO than at 60 mg/kg/da y DFO, and fecal iron excretion became a relatively larger proportion of total excretion at higher doses. Subsequent treatment for 3 months with 150 mg/kg/day DFO caused a 33% to 60% reduction in serum ferritin and demonstrable improvement in hepatic function in all patients. No toxicity was encountered, but DFO at 180 mg/kg/day was associated with a significant increase in fecal zinc excretion when compared with tha t observed at lower doses.