Hydroxyurea: effects on hemoglobin F production in patients with sickle cell anemia [see comments]

摘要: Patients with sickle cell anemia were treated daily doses of hydroxyurea, to assess pharmacokinetics, toxicity, and increase in fetal hemoglobin (Hb) production response the drug. Plasma hydroxyurea clearances not a useful guide maximum tolerated The mean single oral dose that could be maintained for at least 16 weeks was 21 mg/kg (range, 10 35 mg/kg). Among 32 patients, last HbF levels 1.9% 26.3% (mean, 14.9%) increases over initial values 1.4% 20.2% 11.2%). most significant predictors plasma level, white blood count concentration. Last related beta globin haplotype or alpha gene number. No serious toxicity encountered. Clinically bone marrow depression avoided, chromosome abnormalities after 2 years treatment no greater than those observed before treatment. period observation has been too short evaluate risk carcinogenesis. Patient's red cells developed striking macrocytosis. Median Hb concentrations did change. increased, on average 1.2 g/dL, but serum erythropoietin increased. Patients' body weights some returned work school, conclusions regarding therapeutic efficacy drawn from this uncontrolled open-label study.