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Hematologic responses of patients with sickle cell disease to treatment with hydroxyurea.

Abstract

Because fetal hemoglobin contains gammaglobin chains instead of beta chains, it is not affected by the genetic defect that causes sickle cell disease. Increased levels of fetal hemoglobin decrease the tendency toward intracellular polymerization of sickle hemoglobin that characterizes this disease. Hydroxyurea is one of several cytostatic agents that have been shown to increase the production of fetal hemoglobin in some patients with sickle cell disease. We studied the effects of hydroxyurea administration in 10 hospitalized patients with sickle cell disease, each of whom was treated for three months. Seven patients responded with a 2- to 10-fold increase in fetal hemoglobin, from a mean (+/- SD) of 1.6 +/- 1.6 percent of total hemoglobin to 6.8 +/- 4.7 percent; three patients had fetal-hemoglobin levels of 10 to 15 percent of total hemoglobin. Three did not respond to treatment. Four of the patients who responded were retreated with hydroxyurea after one to four months without treatment and were found to have larger increases in fetal-hemoglobin levels. In most patients, levels were still rising at the end of the study, even after 90 days of therapy. Fetal-hemoglobin levels tended to peak at dosages of hydroxyurea that were myelosuppressive. In the patients who responded to treatment, there were significant increases in the percentage of reticulocytes and erythrocytes containing fetal hemoglobin and in the amount of fetal hemoglobin within these cells. The percentage of dense red cells decreased in the patients who responded to treatment. The tendency toward intracellular polymerization at physiologic oxygen saturation was reduced by about 33 percent in the cells containing fetal hemoglobin, whereas there was no change in the other cells. We conclude that hydroxyurea is effective in increasing the production of fetal hemoglobin, which in this study was found to be associated with a small decrease in hemolysis and an increase in hemoglobin levels despite myelosuppression. Controlled, prospective trials are necessary to establish whether these effects will lead to clinical benefit.

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  • Authors+Show Affiliations

    ,

    Laboratory of Chemical Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892.

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    Source

    The New England journal of medicine 322:15 1990 Apr 12 pg 1037-45

    MeSH

    Adult
    Anemia, Sickle Cell
    Blood Cell Count
    Bone Marrow
    Female
    Fetal Hemoglobin
    Hematopoiesis
    Hemoglobin, Sickle
    Hemoglobins
    Humans
    Hydroxyurea
    Male
    Polymers

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    1690857

    Citation

    Rodgers, G P., et al. "Hematologic Responses of Patients With Sickle Cell Disease to Treatment With Hydroxyurea." The New England Journal of Medicine, vol. 322, no. 15, 1990, pp. 1037-45.
    Rodgers GP, Dover GJ, Noguchi CT, et al. Hematologic responses of patients with sickle cell disease to treatment with hydroxyurea. N Engl J Med. 1990;322(15):1037-45.
    Rodgers, G. P., Dover, G. J., Noguchi, C. T., Schechter, A. N., & Nienhuis, A. W. (1990). Hematologic responses of patients with sickle cell disease to treatment with hydroxyurea. The New England Journal of Medicine, 322(15), pp. 1037-45.
    Rodgers GP, et al. Hematologic Responses of Patients With Sickle Cell Disease to Treatment With Hydroxyurea. N Engl J Med. 1990 Apr 12;322(15):1037-45. PubMed PMID: 1690857.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Hematologic responses of patients with sickle cell disease to treatment with hydroxyurea. AU - Rodgers,G P, AU - Dover,G J, AU - Noguchi,C T, AU - Schechter,A N, AU - Nienhuis,A W, PY - 1990/4/12/pubmed PY - 1990/4/12/medline PY - 1990/4/12/entrez SP - 1037 EP - 45 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 322 IS - 15 N2 - Because fetal hemoglobin contains gammaglobin chains instead of beta chains, it is not affected by the genetic defect that causes sickle cell disease. Increased levels of fetal hemoglobin decrease the tendency toward intracellular polymerization of sickle hemoglobin that characterizes this disease. Hydroxyurea is one of several cytostatic agents that have been shown to increase the production of fetal hemoglobin in some patients with sickle cell disease. We studied the effects of hydroxyurea administration in 10 hospitalized patients with sickle cell disease, each of whom was treated for three months. Seven patients responded with a 2- to 10-fold increase in fetal hemoglobin, from a mean (+/- SD) of 1.6 +/- 1.6 percent of total hemoglobin to 6.8 +/- 4.7 percent; three patients had fetal-hemoglobin levels of 10 to 15 percent of total hemoglobin. Three did not respond to treatment. Four of the patients who responded were retreated with hydroxyurea after one to four months without treatment and were found to have larger increases in fetal-hemoglobin levels. In most patients, levels were still rising at the end of the study, even after 90 days of therapy. Fetal-hemoglobin levels tended to peak at dosages of hydroxyurea that were myelosuppressive. In the patients who responded to treatment, there were significant increases in the percentage of reticulocytes and erythrocytes containing fetal hemoglobin and in the amount of fetal hemoglobin within these cells. The percentage of dense red cells decreased in the patients who responded to treatment. The tendency toward intracellular polymerization at physiologic oxygen saturation was reduced by about 33 percent in the cells containing fetal hemoglobin, whereas there was no change in the other cells. We conclude that hydroxyurea is effective in increasing the production of fetal hemoglobin, which in this study was found to be associated with a small decrease in hemolysis and an increase in hemoglobin levels despite myelosuppression. Controlled, prospective trials are necessary to establish whether these effects will lead to clinical benefit. SN - 0028-4793 UR - https://www.unboundmedicine.com/medline/citation/1690857/Hematologic_responses_of_patients_with_sickle_cell_disease_to_treatment_with_hydroxyurea_ L2 - https://www.nejm.org/doi/10.1056/NEJM199004123221504?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=www.ncbi.nlm.nih.gov DB - PRIME DP - Unbound Medicine ER -