Fetal hemoglobin (Hb F) production is augmented in sickle cell anemia patients treated with hydroxyurea. The optimal therapeutic dosage and schedule, the long and short term benefits and risks, the characteristics of patients likely to respond, and the mechanism of drug action are all unknown. The proposed study is designed to offer to selected patients with severe symptomatic sickle cell anemia treatment with hydroxyurea to increase their production of fetal hemoglobin in an effort to ameliorate the course of their disease. A comparison of drug doses and schedules will be performed to optimize therapy. Pharmackinetic and pharmacodynamic studies are included to determine to what extent the interpatient variability in response that has been reported is due to drug metabolism and/or excretion. In addition, molecular-cellular studies are planned to determine whether gene amplification plays a role in the augmentation of Hb F production.
