Hydroxyurea: effects on hemoglobin F production in patients with sickle cell anemia.

Pubmed ID: 1375104

Journal: Blood

Publication Date: May 15, 1992

Affiliation: Johns Hopkins University School of Medicine, Baltimore, MD.

MeSH Terms: Humans, Male, Adult, Female, Haplotypes, Anemia, Sickle Cell, Regression Analysis, Pain, Fetal Hemoglobin, Globins, Alanine Transaminase, Dose-Response Relationship, Drug, Leukocyte Count, Platelet Count, Hydroxyurea, Chromosome Aberrations, Chromosome Disorders, Erythrocyte Count, Karyotyping

Grants: RR00046, RR-0035, RR-00722

Authors: Ballas SK, Charache S, Moore RD, Dover GJ, Orringer EP, Eckert S, Koshy M, Milner PF, Phillips G, Platt OS

Cite As: Charache S, Dover GJ, Moore RD, Eckert S, Ballas SK, Koshy M, Milner PF, Orringer EP, Phillips G Jr, Platt OS. Hydroxyurea: effects on hemoglobin F production in patients with sickle cell anemia. Blood 1992 May 15;79(10):2555-65.

Studies:

Abstract

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