EFFECT OF HYDROXYUREA ON THE FREQUENCY OF PAINFUL CRISES IN SICKLE-CELL-ANEMIA

Background. In a previous open-label study of hydroxyurea therapy, the synthesis of fetal hemoglobin increased in most patients with sickle cell anemia, with only mild myelotoxicity. By inhibiting sickling, inc reased levels of fetal hemoglobin might decrease the frequency of pain ful crises. Methods. In a double-blind, randomized clinical trial, we tested the efficacy of hydroxyurea in reducing the frequency of painfu l crises in adults with a history of three or more such crises per yea r. The trial was stopped after a mean follow-up of 21 months. Results. Among 148 men and 151 women studied at 21 clinics, the 152 patients a ssigned to hydroxyurea treatment had lower annual rates of crises than the 147 patients given placebo (median, 2.5 vs. 4.5 crises per year, P<0.001). The median times to the first crisis (3.0 vs. 1.5 months, P= 0.01) and the second crisis (8.8 vs. 4.6 months, P<0.001) were longer with hydroxyurea treatment. Fewer patients assigned to hydroxyurea had chest syndrome (25 vs, 51, P<0.001), and fewer underwent transfusions (48 vs. 73, P=0.001). At the end of the study, the doses of hydroxyur ea ranged from 0 to 35 mg per kilogram of body weight per day. Treatme nt with hydroxyurea did not cause any important adverse effects.Conclu sions. Hydroxyurea therapy can ameliorate the clinical course of sickl e cell anemia in some adults with three or more painful crises per yea r, Maximal tolerated doses of hydroxyurea may not be necessary to achi eve a therapeutic effect. The beneficial effects of hydroxyurea do not become manifest for several months, and its use must be carefully mon itored, The long-term safety of hydroxyurea in patients with sickle ce ll anemia is uncertain.