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An adequate transfusion program for patients with thalassemia major can prevent death from anemia in infancy and permit normal growth and development during childhood. Because the body lacks any effective means for excreting excess iron, transfusion therapy results in a progressive accumulation of iron, which may be augmented by iron absorbed from the diet as a result of the increased ineffective erythropoiesis1 . Eventually, extensive iron-induced injury develops in the liver, pancreas, heart, and other organs. The severity of iron toxicity seems to be related to the magnitude of the body iron burden2 ,3 . Without treatment to remove the excess iron, almost all patients with thalassemia major who regularly undergo transfusions will accumulate toxic amounts of iron by the age of 10 years or earlier and acquire potentially lethal iron burdens by early adolescence.
Deferoxamine mesylate, a naturally occurring trihydroxamic acid produced by Streptomyces pilosus, increases urinary iron excretion in patients with thalassemia major4 and is the only iron-chelating agent approved for clinical use5 . Therapeutic trials of deferoxamine administered intramuscularly,3 intravenously,6 or subcutaneously7 have shown that regular chelation therapy can decrease hepatic iron,8 ameliorate cardiac,9 ,10 pancreatic,11 and other organ dysfunction,12 ,13 improve growth and sexual maturation,14 ,15 and increase survival16 ,17 in thalassemia major. Although chelation therapy benefits many patients, others continue to have organ dysfunction and die, sometimes despite intensive treatment with deferoxamine18 . The reasons for these apparent differences in the response to chelation therapy are unknown.
We report here the results of a 10-year prospective study of patients with thalassemia major in whom we examined the relations among the amount of iron acquired by transfusion before chelation therapy, the total transfusional iron load accumulated, the amount of deferoxamine administered, the body iron burden as assessed by noninvasive measurements of hepatic iron stores, and clinical outcome as determined by periodic evaluations.
Methods
Patients
We studied 59 patients with thalassemia major (30 of whom were female and 29 male, ranging in age from 7 to 31 years when last seen) who were evaluated periodically in the Clinical Hematology Branch of the National Heart, Lung, and Blood Institute, National Institutes of Health. The patients were given transfusions of red cells as needed to raise their hemoglobin level from 8 to 9 g...