title: Immunologic effects of hydroxyurea in sickle cell anemia.
abstract: 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.
authors.affiliation: Eudowood Division of Allergy and Immunology, Department of Pediatrics, and.
authors.forename: Howard M
authors.initials: HM
authors.lastname: Lederman
authors.affiliation: Clinical Trials and Surveys Corp, Owings Mills, Maryland;
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Connolly
authors.affiliation: Pediatric Hematology, Children's Mercy Hospital, Kansas City, Missouri;
authors.forename: Ram
authors.initials: R
authors.lastname: Kalpatthi
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio;
authors.forename: Russell E
authors.initials: RE
authors.lastname: Ware
authors.affiliation: Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee;
authors.forename: Winfred C
authors.initials: WC
authors.lastname: Wang
authors.affiliation: Division of Hematology, Department of Pediatrics, Children's National Medical Center, Washington, District of Columbia; and.
authors.forename: Lori
authors.initials: L
authors.lastname: Luchtman-Jones
authors.affiliation: National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Myron
authors.initials: M
authors.lastname: Waclawiw
authors.affiliation: National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Goldsmith
authors.affiliation: Eudowood Division of Allergy and Immunology, Department of Pediatrics, and.
authors.forename: Andrea
authors.initials: A
authors.lastname: Swift
authors.affiliation: Division of Hematology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland; jcasella@jhmi.edu.
authors.forename: James F
authors.initials: JF
authors.lastname: Casella
mesh_terms: D000755:Anemia, Sickle Cell / Q000188:drug therapy* / Q000276:immunology*; D000986:Antisickling Agents / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D022542:Measles-Mumps-Rubella Vaccine / Q000008:administration & dosage / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D000986:Antisickling Agents; D022542:Measles-Mumps-Rubella Vaccine; D006918:Hydroxyurea
keywords: hydroxyurea; immunology; sickle cell disease; vaccines