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Increasing fetal hemoglobin production in sickle cell disease: results of clinical trials.
Prog Clin Biol Res 1987; 251:455-66PC

Abstract

Five years experience using 5AZA and HU in a limited number of patients with SS disease, have resulted in the following conclusions. First, these drugs can rapidly induce increases in HbF production. Rapid increases in HbF production are not associated with reductions in overall reticulocyte levels, or reductions in late erythroid precursors, such as CFU-E. Indeed, where higher doses of these drugs are used or where the patient is unable to clear the drug rapidly, cytotoxicity is associated with reduced HbF production. These drugs not only increase the number of cells containing HbF, but also increase the MCV and the MCH of both F cells and non-F cells. Uncontrolled clinical trials suggest that the clinical severity of the disease measured by reduction in anemia and fewer vasoocclusive SS crises, may result from use of these drugs. The mechanisms by which these drugs result in increased F-cell production and increased MCH of F cells and non-F cells, may be due to their ability to reversibly block cells during their cell-cycle. This reversible blockade does not inhibit either on-going protein production or the establishment of origins of replications of DNA. Even though the mechanisms whereby the increased HbF production is not known, early clinical results seem to justify the initiation of controlled clinical trials of HU in severely affected SS patients.

Authors+Show Affiliations

Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2448813

Citation

Dover, G J., and S Charache. "Increasing Fetal Hemoglobin Production in Sickle Cell Disease: Results of Clinical Trials." Progress in Clinical and Biological Research, vol. 251, 1987, pp. 455-66.
Dover GJ, Charache S. Increasing fetal hemoglobin production in sickle cell disease: results of clinical trials. Prog Clin Biol Res. 1987;251:455-66.
Dover, G. J., & Charache, S. (1987). Increasing fetal hemoglobin production in sickle cell disease: results of clinical trials. Progress in Clinical and Biological Research, 251, pp. 455-66.
Dover GJ, Charache S. Increasing Fetal Hemoglobin Production in Sickle Cell Disease: Results of Clinical Trials. Prog Clin Biol Res. 1987;251:455-66. PubMed PMID: 2448813.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increasing fetal hemoglobin production in sickle cell disease: results of clinical trials. AU - Dover,G J, AU - Charache,S, PY - 1987/1/1/pubmed PY - 1987/1/1/medline PY - 1987/1/1/entrez SP - 455 EP - 66 JF - Progress in clinical and biological research JO - Prog. Clin. Biol. Res. VL - 251 N2 - Five years experience using 5AZA and HU in a limited number of patients with SS disease, have resulted in the following conclusions. First, these drugs can rapidly induce increases in HbF production. Rapid increases in HbF production are not associated with reductions in overall reticulocyte levels, or reductions in late erythroid precursors, such as CFU-E. Indeed, where higher doses of these drugs are used or where the patient is unable to clear the drug rapidly, cytotoxicity is associated with reduced HbF production. These drugs not only increase the number of cells containing HbF, but also increase the MCV and the MCH of both F cells and non-F cells. Uncontrolled clinical trials suggest that the clinical severity of the disease measured by reduction in anemia and fewer vasoocclusive SS crises, may result from use of these drugs. The mechanisms by which these drugs result in increased F-cell production and increased MCH of F cells and non-F cells, may be due to their ability to reversibly block cells during their cell-cycle. This reversible blockade does not inhibit either on-going protein production or the establishment of origins of replications of DNA. Even though the mechanisms whereby the increased HbF production is not known, early clinical results seem to justify the initiation of controlled clinical trials of HU in severely affected SS patients. SN - 0361-7742 UR - https://www.unboundmedicine.com/medline/citation/2448813/Increasing_fetal_hemoglobin_production_in_sickle_cell_disease:_results_of_clinical_trials_ L2 - http://www.diseaseinfosearch.org/result/6589 DB - PRIME DP - Unbound Medicine ER -