{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:55:43Z","timestamp":1791204943163,"version":"4.1.0"},"reference-count":27,"publisher":"American Academy of Pediatrics (AAP)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,10,1]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND AND OBJECTIVE:<\/jats:title>\n                    <jats:p>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\u2019s effects on immune function in SCD. Because hydroxyurea inhibits ribonucleotide reductase, causing cell cycle arrest at the G1\u2013S interface, we postulated that hydroxyurea might delay transition from naive to memory T cells, with inhibition of immunologic maturation and vaccine responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1542\/peds.2014-0571","type":"journal-article","created":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T20:42:32Z","timestamp":1409604152000},"page":"686-695","source":"Crossref","is-referenced-by-count":44,"title":["Immunologic Effects of Hydroxyurea in Sickle Cell Anemia"],"prefix":"10.1542","volume":"134","author":[{"given":"Howard M.","family":"Lederman","sequence":"first","affiliation":[{"name":"Eudowood Division of Allergy and Immunology, Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret A.","family":"Connolly","sequence":"additional","affiliation":[{"name":"Clinical Trials and Surveys Corp, Owings Mills, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram","family":"Kalpatthi","sequence":"additional","affiliation":[{"name":"Pediatric Hematology, Children\u2019s Mercy Hospital, Kansas City, Missouri;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell E.","family":"Ware","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winfred C.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology, St. Jude Children\u2019s Research Hospital, Memphis, Tennessee;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori","family":"Luchtman-Jones","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Pediatrics, Children\u2019s National Medical Center, Washington, District of Columbia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myron","family":"Waclawiw","sequence":"additional","affiliation":[{"name":"National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan C.","family":"Goldsmith","sequence":"additional","affiliation":[{"name":"National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Swift","sequence":"additional","affiliation":[{"name":"Eudowood Division of Allergy and Immunology, Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F.","family":"Casella","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2014,10,1]]},"reference":[{"issue":"12","key":"2021120903415722300_B1","doi-asserted-by":"crossref","first-page":"932","DOI":"10.7326\/0003-4819-148-12-200806170-00220","article-title":"National Institutes of Health Consensus Development Conference statement: hydroxyurea treatment for sickle cell disease.","volume":"148","author":"Brawley","year":"2008","journal-title":"Ann Intern Med"},{"issue":"9778","key":"2021120903415722300_B2","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1016\/S0140-6736(11)60355-3","article-title":"Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG).","volume":"377","author":"Wang","year":"2011","journal-title":"Lancet"},{"issue":"2","key":"2021120903415722300_B3","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1097\/00005792-197103000-00002","article-title":"Bacterial infection and sickle cell anemia. An analysis of 250 infections in 166 patients and a review of the literature.","volume":"50","author":"Barrett-Connor","year":"1971","journal-title":"Medicine (Baltimore)"},{"issue":"4","key":"2021120903415722300_B4","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1067\/S0022-3476(03)00331-7","article-title":"Invasive pneumococcal infections in children with sickle cell disease in the era of penicillin prophylaxis, antibiotic resistance, and 23-valent pneumococcal polysaccharide vaccination.","volume":"143","author":"Adamkiewicz","year":"2003","journal-title":"J Pediatr"},{"issue":"1","key":"2021120903415722300_B5","first-page":"CD003885","article-title":"Pneumococcal vaccines for sickle cell disease.","author":"Davies","year":"2004","journal-title":"Cochrane Database Syst Rev"},{"issue":"3","key":"2021120903415722300_B6","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1542\/peds.2007-0018","article-title":"Effectiveness of the 7-valent pneumococcal conjugate vaccine in children with sickle cell disease in the first decade of life.","volume":"121","author":"Adamkiewicz","year":"2008","journal-title":"Pediatrics"},{"issue":"6","key":"2021120903415722300_B7","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1097\/00005792-199611000-00002","article-title":"Hydroxyurea and sickle cell anemia. Clinical utility of a myelosuppressive \u201cswitching\u201d agent.","volume":"75","author":"Charache","year":"1996","journal-title":"Medicine (Baltimore)"},{"issue":"3","key":"2021120903415722300_B8","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1182\/blood.V89.3.1078","article-title":"Fetal hemoglobin in sickle cell anemia: determinants of response to hydroxyurea.","volume":"89","author":"Steinberg","year":"1997","journal-title":"Blood"},{"issue":"6","key":"2021120903415722300_B9","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1182\/blood.V88.6.1960.bloodjournal8861960","article-title":"Hydroxyurea for treatment of severe sickle cell anemia: a pediatric clinical trial.","volume":"88","author":"Ferster","year":"1996","journal-title":"Blood"},{"issue":"4","key":"2021120903415722300_B10","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/S0022-3476(96)70121-X","article-title":"Clinical and hematologic effects of hydroxyurea in children with sickle cell anemia.","volume":"129","author":"Jayabose","year":"1996","journal-title":"J Pediatr"},{"key":"2021120903415722300_B11","first-page":"253","article-title":"Hydroxyurea","volume-title":"Cancer Chemotherapy and Biotherapy","author":"Donehower","year":"1996","edition":"2nd ed."},{"issue":"10","key":"2021120903415722300_B12","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1038\/sj.leu.2404326","article-title":"Loss of antibodies and response to (re-)vaccination in children after treatment for acute lymphocytic leukemia: a systematic review.","volume":"20","author":"van Tilburg","year":"2006","journal-title":"Leukemia"},{"issue":"7","key":"2021120903415722300_B13","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1002\/pbc.23043","article-title":"Multivariate analysis of the relation between immune dysfunction and treatment intensity in children with acute lymphoblastic leukemia.","volume":"56","author":"Ek","year":"2011","journal-title":"Pediatr Blood Cancer"},{"issue":"8","key":"2021120903415722300_B14","doi-asserted-by":"crossref","first-page":"487","DOI":"10.3928\/0090-4481-19990801-06","article-title":"Immunizations for the immunocompromised child.","volume":"28","author":"McFarland","year":"1999","journal-title":"Pediatr Ann"},{"issue":"6","key":"2021120903415722300_B15","doi-asserted-by":"crossref","DOI":"10.1542\/peds.109.6.e91","article-title":"Current chemotherapy protocols for childhood acute lymphoblastic leukemia induce loss of humoral immunity to viral vaccination antigens.","volume":"109","author":"Nilsson","year":"2002","journal-title":"Pediatrics"},{"issue":"11","key":"2021120903415722300_B16","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1097\/00043426-200411000-00008","article-title":"Intensive treatment for childhood acute lymphoblastic leukemia reduces immune responses to diphtheria, tetanus, and Haemophilus influenzae type b.","volume":"26","author":"Ek","year":"2004","journal-title":"J Pediatr Hematol Oncol"},{"key":"2021120903415722300_B17","unstructured":"American Cancer Society Web Site. Available at: www.cancer.org\/treatment\/treatmentsandsideeffects\/guidetocancerdrugs\/hydroxyurea"},{"issue":"6","key":"2021120903415722300_B18","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1097\/00006454-198706000-00006","article-title":"Serum antibodies to pneumococcal C polysaccharide in children: response to acute pneumococcal otitis media or to vaccination.","volume":"6","author":"Koskela","year":"1987","journal-title":"Pediatr Infect Dis J"},{"issue":"5","key":"2021120903415722300_B19","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1128\/cdli.2.5.590-597.1995","article-title":"Assignment of weight-based antibody units to a human antipneumococcal standard reference serum, lot 89-S.","volume":"2","author":"Quataert","year":"1995","journal-title":"Clin Diagn Lab Immunol"},{"key":"2021120903415722300_B20","volume-title":"Program ELISA User\u2019s Manual","author":"Plikaytis","year":"1993"},{"issue":"5","key":"2021120903415722300_B21","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.jaci.2003.07.003","article-title":"Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study.","volume":"112","author":"Shearer","year":"2003","journal-title":"J Allergy Clin Immunol"},{"issue":"8","key":"2021120903415722300_B22","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1182\/blood.V85.8.2091.bloodjournal8582091","article-title":"Blood transfusions and immunophenotypic alterations of lymphocyte subsets in sickle cell anemia.","volume":"85","author":"Wong","year":"1995","journal-title":"Blood"},{"issue":"19","key":"2021120903415722300_B23","doi-asserted-by":"crossref","first-page":"3816","DOI":"10.1016\/j.vaccine.2007.01.119","article-title":"Estimating the protective concentration of anti-pneumococcal capsular polysaccharide antibodies.","volume":"25","author":"Siber","year":"2007","journal-title":"Vaccine"},{"issue":"3","key":"2021120903415722300_B24","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.jaci.2012.07.002","article-title":"Use and interpretation of diagnostic vaccination in primary immunodeficiency: a working group report of the Basic and Clinical Immunology Interest Section of the American Academy of Allergy, Asthma & Immunology.","volume":"130","author":"Orange","year":"2012","journal-title":"J Allergy Clin Immunol"},{"issue":"8","key":"2021120903415722300_B25","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1097\/00006454-199608000-00010","article-title":"Antibody persistence after primary measles-mumps-rubella vaccine and response to a second dose given at four to six vs. eleven to thirteen years.","volume":"15","author":"Johnson","year":"1996","journal-title":"Pediatr Infect Dis J"},{"key":"2021120903415722300_B26","first-page":"489","volume-title":"Red Book: 2012 Report of the Committee on Infectious Diseases","author":"American Academy of Pediatrics","year":"2012","edition":"29th ed."},{"issue":"22","key":"2021120903415722300_B27","doi-asserted-by":"crossref","first-page":"4304","DOI":"10.1182\/blood-2012-03-419879","article-title":"Impact of hydroxyurea on clinical events in the BABY HUG trial.","volume":"120","author":"Thornburg","year":"2012","journal-title":"Blood"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/134\/4\/686\/1100499\/peds_2014-0571.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/134\/4\/686\/1100499\/peds_2014-0571.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T14:18:27Z","timestamp":1639059507000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/134\/4\/686\/32904\/Immunologic-Effects-of-Hydroxyurea-in-Sickle-Cell"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,1]]},"references-count":27,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2014,10,1]]},"published-print":{"date-parts":[[2014,10,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.2014-0571","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718553193.793499670","asserted-by":"object"}]},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,1]]}}}