A prospective evaluation of iron chelation therapy in children with severe beta-thalassemia. A six-year study
H. S. Maurer, J. D. Lloyd-Still, C. Ingrisano, F. Gonzalez-Crussi and G. R. Honig
Division of Hematology, Children's Memorial Hospital, Northwestern University Medical School, Chicago, Illinois.
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.
