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Immunologic effects of hydroxyurea in sickle cell anemia.

Author(s): Lederman HM(1), Connolly MA(2), Kalpatthi R(3), Ware RE(4), Wang WC(5), Luchtman-Jones L(6), Waclawiw M(7), Goldsmith JC(7), Swift A(1), Casella JF(8); BABY HUG Investigators.

Affiliation(s): Author information: (1)Eudowood Division of Allergy and Immunology, Department of Pediatrics, and. (2)Clinical Trials and Surveys Corp, Owings Mills, Maryland; (3)Pediatric Hematology, Children's Mercy Hospital, Kansas City, Missouri; (4)Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; (5)Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee; (6)Division of Hematology, Department of Pediatrics, Children's National Medical Center, Washington, District of Columbia; and. (7)National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland. (8)Division of Hematology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland; jcasella@jhmi.edu.

Publication date & source: 2014, Pediatrics. , 134(4):686-95

BACKGROUND AND OBJECTIVE: Susceptibility to encapsulated bacteria is well known in sickle cell disease (SCD). Hydroxyurea use is common in adults and children with SCD, but little is known about hydroxyurea's effects on immune function in SCD. Because hydroxyurea inhibits ribonucleotide reductase, causing cell cycle arrest at the G1-S interface, we postulated that hydroxyurea might delay transition from naive to memory T cells, with inhibition of immunologic maturation and vaccine responses. METHODS: T-cell subsets, naive and memory T cells, and antibody responses to pneumococcal and measles, mumps, and rubella vaccines were measured among participants in a multicenter, randomized, double-blind, placebo-controlled trial of hydroxyurea in infants and young children with SCD (BABY HUG). RESULTS: Compared with placebo, hydroxyurea treatment resulted in significantly lower total lymphocyte, CD4, and memory T-cell counts; however, these numbers were still within the range of historical healthy controls. Antibody responses to pneumococcal vaccination were not affected, but a delay in achieving protective measles antibody levels occurred in the hydroxyurea group. Antibody levels to measles, mumps, and rubella showed no differences between groups at exit, indicating that effective immunization can be achieved despite hydroxyurea use. CONCLUSIONS: Hydroxyurea does not appear to have significant deleterious effects on the immune function of infants and children with SCD. Additional assessments of lymphocyte parameters of hydroxyurea-treated children may be warranted. No changes in current immunization schedules are recommended; however, for endemic disease or epidemics, adherence to accelerated immunization schedules for the measles, mumps, and rubella vaccine should be reinforced.

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