LONG-TERM SAFETY AND EFFECTIVENESS OF IRON-CHELATION THERAPY WITH DEFERIPRONE FOR THALASSEMIA MAJOR

Background Deferiprone is an orally active iron-chelation agent that i s being evaluated as a treatment for iron overload in thalassemia majo r. Studies in an animal model showed that prolonged treatment is assoc iated with a decline in the effectiveness of deferiprone and exacerbat ion of hepatic fibrosis. Methods Hepatic iron stores were determined y early by chemical analysis of liver-biopsy specimens, magnetic suscept ometry, or both. Three hepatopathologists who were unaware of the pati ents' clinical status, the time at which the specimens were obtained, and the iron content of the specimens examined 72 biopsy specimens fro m 19 patients treated with deferiprone for more than one year. For com parison, 48 liver-biopsy specimens obtained from 20 patients treated w ith parenteral deferoxamine far more than one year were similarly revi ewed. Results Of the 19 patients treated with deferiprone, 18 had rece ived the drug continuously for a mean (+/-SE) of 4.6+/-0.3 years. At t he final analysis, 7 of the 18 had hepatic iron concentrations of at l east 80 mu mol per gram of liver, wet weight (the value above which th ere is an increased risk of cardiac disease and early death in patient s with thalassemia major). Of 19 patients in whom multiple biopsies we re performed over a period of more than one year, 14 could be evaluate d for progression of hepatic fibrosis; of the 20 deferoxamine-treated patients, 12 could be evaluated for progression. Five deferiprone-trea ted patients had progression of fibrosis, as compared with none of tho se given deferoxamine (P=0.04). By the life-table method, we estimated that the median time to progression of fibrosis was 3.2 years in defe riprone-treated patients. After adjustment for the initial hepatic iro n concentration, the estimated odds of progression of fibrosis increas ed by a factor of 5.8 (95 percent confidence interval, 1.1 to 29.6) wi th each additional year of deferiprone treatment. Conclusions Deferipr one does not adequately control body iron burden in patients with thal assemia and may worsen hepatic fibrosis. (N Engl J Med 1998;339:417-23 .) (C)1998, Massachusetts Medical Society.