TY - JOUR
T1 - Immunologic effects of hydroxyurea in sickle cell anemia
AU - Lederman, Howard M.
AU - Connolly, Margaret A.
AU - Kalpatthi, Ram
AU - Ware, Russell E.
AU - Wang, Winfred C.
AU - Luchtman-Jones, Lori
AU - Waclawiw, Myron
AU - Goldsmith, Jonathan C.
AU - Swift, Andrea
AU - Casella, James F.
N1 - Publisher Copyright:
Copyright © 2014 by the American Academy of Pediatrics.
PY - 2014
Y1 - 2014
N2 - 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 ribonu-cleotide 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, doubleblind, 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.
AB - 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 ribonu-cleotide 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, doubleblind, 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.
KW - Hydroxyurea
KW - Immunology
KW - Sickle cell disease
KW - Vaccines
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U2 - 10.1542/peds.2014-0571
DO - 10.1542/peds.2014-0571
M3 - Article
C2 - 25180279
AN - SCOPUS:84925279511
SN - 0031-4005
VL - 134
SP - 686
EP - 695
JO - Pediatrics
JF - Pediatrics
IS - 4
ER -