Cited by 2,340Hemoglobinopathies and Related DisordersBlood groups and transfusionHemophilia Treatment and Research

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Effect of Hydroxyurea on the Frequency of Painful Crises in Sickle Cell Anemia

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Charache, Samuel, Terrin, Michael L., Moore, Richard D., Dover, George J., Barton, Franca B., Eckert, Susan V., McMahon, Robert P., Bonds, Duane R.·1995·New England Journal of Medicine

DOI 10.1056/nejm199505183322001

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Abstract

BACKGROUND: In a previous open-label study of hydroxyurea therapy, the synthesis of fetal hemoglobin increased in most patients with sickle cell anemia, with only mild myelotoxicity. By inhibiting sickling, increased levels of fetal hemoglobin might decrease the frequency of painful crises. METHODS: In a double-blind, randomized clinical trial, we tested the efficacy of hydroxyurea in reducing the frequency of painful crises in adults with a history of three or more such crises per year. The trial was stopped after a mean follow-up of 21 months. RESULTS: Among 148 men and 151 women studied at 21 clinics, the 152 patients assigned to hydroxyurea treatment had lower annual rates of crises than the 147 patients given placebo (median, 2.5 vs. 4.5 crises per year, P < 0.001). The median times to the first crisis (3.0 vs. 1.5 months, P = 0.01) and the second crisis (8.8 vs. 4.6 months, P < 0.001) were longer with hydroxyurea treatment. Fewer patients assigned to hydroxyurea had chest syndrome (25 vs. 51, P < 0.001), and fewer underwent transfusions (48 vs. 73, P = 0.001). At the end of the study, the doses of hydroxyurea ranged from 0 to 35 mg per kilogram of body weight per day. Treatment with hydroxyurea did not cause any important adverse effects. CONCLUSIONS: Hydroxyurea therapy can ameliorate the clinical course of sickle cell anemia in some adults with three or more painful crises per year. Maximal tolerated doses of hydroxyurea may not be necessary to achieve a therapeutic effect. The beneficial effects of hydroxyurea do not become manifest for several months, and its use must be carefully monitored. The long-term safety of hydroxyurea in patients with sickle cell anemia is uncertain.

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Yates, A. M., Aygün, B., Nuss, R., Rogers, Z. R., Hematology/Oncology, S. O., Wetmore, C., Dickens, D., Majumdar, S., Stoffman, J. M., Warwick, A. B., et al. (2024) · PEDIATRICS · doi:10.1542/peds.2024-066842 · Cited by 30
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“In the pivotal trial, hydroxyurea (15-35 mg/kg) increased HbF for 2 years in ~50% of the adult SCD patients treated.(30,31) As predicted, HbF increases with hydroxyurea correlated strongly with longer RBC half-life,(32,33) fewer pain crises,(31) and better quality of life(34) (the benefits of hydroxyurea therapy in si…”
Background
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Moringa oleifera Lamarck (drumstick) Leaf Extract Modulates the Evidences of Hydroxyurea -Induced Testicular Derangement
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Chromosome damage and repair in children with sickle cell anaemia and long‐term hydroxycarbamide exposure
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In vivo and in vitro studies of fetal hemoglobin induction by hydroxyurea in β-thalassemia/hemoglobin E patients
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Brazilian Guidelines for transcranial doppler in children and adolescents with sickle cell disease
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Hydroxyurea therapy of a murine model of sickle cell anemia inhibits the progression of pneumococcal disease by down-modulating E-selectin
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“12) and is associated with significant reductions in acute pain crises, hospitalization rate, time to first and second pain crises, episodes of acute chest syndrome, and the need for transfusions and the number of units transfused.(110) Other beneficial effects of hydroxycarbamide, which are independent of the increas…”
Background
Rheological properties of sickle erythrocytes in patients with sickle‐cell anemia: The effect of hydroxyurea, fetal hemoglobin, and α‐thalassemia
Ballas, S. K., & Connes, P. (2018) · European Journal Of Haematology · doi:10.1111/ejh.13173 · Cited by 28
“…effects of HU included increased Hb F synthesis, Hb levels, mean corpuscular volume (MCV), propor‐ tion of F cells, and red blood cell (RBC) hydration status.1‐4 White blood cell (WBC), platelet, reticulocyte, and dense‐cell counts were aThe investigators were as listed in Charache et al (1995).”
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Optimal suppression of HIV replication by low-dose hydroxyurea through the combination of antiviral and cytostatic (‘virostatic’) mechanisms
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Activation of human γ-globin gene expression via triplex-forming oligonucleotide (TFO)-directed mutations in the γ-globin gene 5′ flanking region
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Introduction
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Acute Chest Syndrome in Sickle Cell Disease
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Pharmacokinetics and bioequivalence of a liquid formulation of hydroxyurea in children with sickle cell anemia
Estepp, J. H., Melloni, C., Thornburg, C. D., Wiczling, P., Rogers, Z. R., Rothman, J., Green, N., Liem, R. I., Brandow, A. M., Crary, S. E., et al. (2015) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.598 · Cited by 27
“Table 4 provides a summary of existing studies assessing the PK properties of HU in patients with SCA.”
BackgroundInfluential
Hydroxyurea in the Management of Thalassemia Intermedia
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Integration of Mobile Health Into Sickle Cell Disease Care to Increase Hydroxyurea Utilization: Protocol for an Efficacy and Implementation Study
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Pulmonary Complications of Sickle Cell Disease
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Comparison of Patients from Nigeria and the USA Highlights Modifiable Risk Factors for Sickle Cell Anemia Complications
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“Hydroxyurea therapy is currently the only therapy that has been shown, in randomized studies, to improve the clinical course of sickle cell anemia (7).”
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A Generalized Estimating Equation Approach for Modeling Random Length Binary Vector Data
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La drépanocytose homozygote après l’âge de 20 ans : suivi d’une cohorte de 108 patients au CHU de Dakar
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Hydroxamide derivatives of short-chain fatty acids are potent inducers of human fetal globin gene expression
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Effects of hydroxurea, stem cell factor, and erythropoietin in combination on fetal hemoglobin in the baboon
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Sickle cell disease and stroke: Primary prevention and transcranial Doppler
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Stroke prevention in sickle cell disease
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Authors: Charache, S., Terrin, M. L., Moore, R. D., Dover, G. J., Barton, F. B., Eckert, S. V., McMahon, R. P., & Bonds, D. R.
Affiliations: Johns Hopkins University (US)
Maryland Medical Research Institute (US)
National Heart, Lung, and Blood Institute (US)
ORCID: Terrin, Michael L.
Moore, Richard D.
Barton, Franca B.
McMahon, Robert P.
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 1995-05-18
Volume: 332
Issue: 20
Pages: 1317-1322
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejm199505183322001
OpenAlex: W2313541759
Semantic Scholar: 2c0939e2f6480b519903bb15870e5b894887e70d
Cited by: 2,340
References: 26
Citations by year: 2026: 67 · 2025: 97 · 2024: 77 · 2023: 88 · 2022: 95 · 2021: 92 · 2020: 80 · 2019: 78 · 2018: 85 · 2017: 104 · 2016: 114 · 2015: 101 · 2014: 82 · 2013: 79 · 2012: 73
FWCI: 34.43
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: Bristol-Myers Squibb
National Institutes of Health (5u01hl045696-05)
National Heart, Lung, and Blood Institute (UO1-HL 45696, UO1 HL 45692, U01HL045692)
National Center for Research Resources (RR00046, M01RR000046)
Topics: Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
Health Sciences › Medicine › Hematology › Blood groups and transfusion
Health Sciences › Medicine › Hematology › Hemophilia Treatment and Research
Keywords: hydroxyurea, sickle cell disease, vaso-occlusive crisis, fetal hemoglobin, blood transfusion, myelosuppression, treatment efficacy, adverse effects
MeSH terms: Adult, Anemia, Sickle Cell, Double-Blind Method, Female, Follow-Up Studies, Humans, Hydroxyurea, Male, Pain

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Effect of Hydroxyurea on the Frequency of Painful Crises in Sickle Cell Anemia

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