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Review
. 2011 May;18(3):158-65.
doi: 10.1097/MOH.0b013e32834521dd.

Hydroxyurea for sickle cell anemia: what have we learned and what questions still remain?

Patrick T McGann  1 , Russell E Ware
Affiliations
Review

Hydroxyurea for sickle cell anemia: what have we learned and what questions still remain?

Patrick T McGann et al. Curr Opin Hematol. 2011 May.

Abstract

Purpose of review: Sickle cell anemia (SCA) is a well characterized severe hematological disorder with substantial morbidity and early mortality. Hydroxyurea is a potent inducer of fetal hemoglobin, and evidence over the past 25 years has documented its laboratory and clinical efficacy for both adults and children with SCA.

Recent findings: The phase III study of hydroxyurea in infants (BABY HUG) has just been completed and preliminary results indicate equivocal benefits for organ protection during the 2-year treatment period, but significant benefits for pain, acute chest syndrome, hospitalizations, and transfusions. Three new reports document the benefits of hydroxyurea on reducing mortality in SCA: two adult trials (LaSHS and MSH) and one pediatric study (Brazilian cohort). Recent results from the HUSTLE protocol suggest minimal genotoxicity or carcinogenicity with long-term hydroxyurea exposure.

Summary: The potential utility of hydroxyurea for all patients with SCA is clear and indisputable. With decades of accumulated evidence and documented efficacy with an acceptable long-term safety profile, it is time to consider hydroxyurea treatment the standard of care for all young patients with SCA. Exporting our knowledge and experience with hydroxyurea to developing nations with large medical burdens from SCA can help relieve global suffering from this condition.

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Figures

Fig 1
Fig 1. Mechanisms of action involved in the beneficial effects of hydroxyurea for sickle cell anemia (20)
Legend: (1) Induction of fetal hemoglobin in erythroid compartment; (2) Marrow cytoxicity and decreased neutrophil and reticulocyte counts; (3) Altered expression of adhesion molecules on circulating neutrophils and reticulocytes decreases adhesiveness and subsequent endothelial damage; (4) Macrocytosis and increased hydration reduces hemolysis and intracellular sickling; (5) Local release of nitric oxide (NO) results in vasodilation. Source: Reference
Fig 2
Fig 2. Hydroxyurea improves survival across SCD phenotypes (40)
Legend: (A) Patients with HbS/β0 thalassemia and hydroxyurea exposure had improved 10-year overall survival (OS) compared to patients without hydroxyurea exposure (87% vs. 54%, p=0.001); (B) HbSS patients receiving hydroxyurea had a 10-year OS of 100% compared to 10% in those without hydroxyurea exposure (p<0.01). Source: Reference
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References

    1. Odame I. Developing a global agenda for sickle cell disease: report of an international symposium and workshop in Cotonou, Republic of Benin. Am J Prev Med. 2010;38(4 Suppl):S571–S575.. ** Comprehensive summary describing the global burden of SCA and plan for partnerships between high-and low-income countries, authored by the director of the Global Sickle Cell Disease Network.

    1. Hassell KL. Population estimates of sickle cell disease in the U.S. Am J Prev Med. 2010;38(4 Suppl):S512–S521. - PubMed
    1. Conley CL, Weatherall DJ, Richardson SN, et al. Hereditary persistence of fetal hemoglobin: a study of 79 affected persons in 15 Negro families in Baltimore. Blood. 1963;21:261–281. - PubMed
    1. Charache S. Fetal hemoglobin, sickling, and sickle cell disease. Adv Pediatr. 1990;37:1–31. - PubMed
    1. Platt OS, Orkin SH, Dover G, et al. Hydroxyurea enhances fetal hemoglobin production in sickle cell anemia. J Clin Invest. 1984;74(2):652–656. - PMC - PubMed

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