A prospective evaluation of iron chelation therapy in children with severe beta-thalassemia. A six-year study.

Sixteen patients (age range, 3 to 17 years) with transfusion-dependent beta-thalassemia major were studied prospectively, beginning at the onset of chelation therapy with deferoxamine (desferrioxamine). A liver biopsy specimen was obtained from each patient at the start of the study, and periodically thereafter. Liver histologic features, iron content, and iron excretion were assessed during the course of the study. Hepatic iron levels from liver biopsy specimens appeared to correlate well with serum ferritin levels in the younger less heavily iron-loaded patients; however, in patients with higher serum ferritin levels, hepatic iron appeared to reach a saturation level. Fourteen of the 16 patients showed a pattern of marbled fibrosis of the liver in their initial biopsy specimens. Follow-up biopsy specimens from nearly all of the patients showed a substantial reduction in iron concentration, but only two of seven patients showed improvement in the degree of hepatic fibrosis three to five years later. Patients less than 8 years old exhibited a normal pattern of linear growth until approximately the age of 10 years, followed by a progressive decrease to the 30th to 40th percentile. Two patients, aged 18 and 22 years, died of cardiac disease during the study. These findings suggest that chelation therapy in patients with transfusion-dependent thalassemia needs to be initiated at an early age, possibly before 3 years, if significant liver fibrosis and growth impairment are to be effectively prevented.