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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