{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T22:34:33Z","timestamp":1773268473205,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,10,8]],"date-time":"2017-10-08T00:00:00Z","timestamp":1507420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Despite the demonstrated efficacy of hydroxyurea therapy, children with sickle cell anaemia in the UK are preferentially managed with supportive care or transfusion. Hydroxyurea is reserved for children with severe disease phenotype. This is in contrast to North America and other countries where hydroxyurea is widely used for children of all clinical phenotypes. The conservative UK practice may in part be due to concerns about toxicity, in particular marrow suppression with high doses, and growth in children.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We monitored 37 paediatric patients with sickle cell anaemia who were treated with hydroxyurea at a single UK treatment centre. Therapy was well tolerated and mild transient cytopenias were the only toxicity observed. Comparative analysis of patients receiving \u226526\u00a0mg\/kg\/day versus\u00a0&lt;26\u00a0mg\/kg\/day demonstrates increasing dose has a significant positive effect on foetal haemoglobin (Hb; 29.2% vs. 20.4%, <jats:italic>P\u00a0<\/jats:italic>=\u00a00.0151), mean cell volume (94.4 vs. 86.5, <jats:italic>P\u00a0<\/jats:italic>=\u00a00.0183) and reticulocyte count (99.66\u00a0\u00d7\u00a010<jats:sup>9<\/jats:sup>\/l vs. 164.3\u00a0\u00d7\u00a010<jats:sup>9<\/jats:sup>\/l, <jats:italic>P\u00a0<\/jats:italic>=\u00a00.0059). Marrow suppression was not a clinical problem with high\u2010dose treatment, Hb 92.25\u00a0g\/l versus 91.81\u00a0g\/l (ns), neutrophil count 3.3\u00a0\u00d7\u00a010<jats:sup>9<\/jats:sup>\/l versus 4.8\u00a0\u00d7\u00a010<jats:sup>9<\/jats:sup>\/l (ns) and platelet count 232.4\u00a0\u00d7\u00a010<jats:sup>9<\/jats:sup>\/l versus 302.2\u00a0\u00d7\u00a010<jats:sup>9<\/jats:sup>\/l (ns). Normal growth rates were maintained in all children. Good adherence to therapy was a significant factor in reducing hospitalisations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study demonstrates the effectiveness and safety in practice of high\u2010dose hydroxyurea as a disease\u2010modifying therapy, which we advocate for all children with sickle cell anaemia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.26833","type":"journal-article","created":{"date-parts":[[2017,10,8]],"date-time":"2017-10-08T11:56:35Z","timestamp":1507463795000},"source":"Crossref","is-referenced-by-count":15,"title":["Hydroxyurea therapy in UK children with sickle cell anaemia: A single\u2010centre experience"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6594-2635","authenticated-orcid":false,"given":"Kate","family":"Phillips","sequence":"first","affiliation":[{"name":"Department of Women's and Children's Health Institute of Translational Medicine University of Liverpool  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Healy","sequence":"additional","affiliation":[{"name":"Department of Haematology and Oncology Alder Hey Children's NHS Foundation Trust  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Haematology and Oncology Alder Hey Children's NHS Foundation Trust  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russell","family":"Keenan","sequence":"additional","affiliation":[{"name":"Department of Haematology and Oncology Alder Hey Children's NHS Foundation Trust  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,10,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00043426-199707000-00009"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60355-3"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199505183322001"},{"key":"e_1_2_7_5_1","unstructured":"NHS Sickle Cell and Thalassaemia Screening Programme.Sickle cell disease in childhood: standards and guidelines for clinical care (2nd edition). 2010."},{"key":"e_1_2_7_6_1","unstructured":"MDSAS.National haemoglobinopathy registry annual report 2015\/16.http:\/\/www.nhr.nhs.uk\/wp-content\/uploads\/2017\/02\/NHR_AnnualReport_201516.pdf."},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25529"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25608"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12323"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-03-419879"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.23365"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.10517"},{"issue":"5","key":"e_1_2_7_13_1","first-page":"1550","article-title":"Safety of hydroxyurea in children with sickle cell anemia: results of the HUG\u2010KIDS study, a phase I\/II trial","volume":"94","author":"Kinney T","year":"1999","journal-title":"Blood."},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-12-4973"},{"issue":"8","key":"e_1_2_7_15_1","first-page":"1559","article-title":"Inhibition of ribonucleoside diphosphate reductase by hydroxyurea","volume":"28","author":"Krakoff I","year":"1968","journal-title":"Cancer Res"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21699"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-05-221333"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199107043250103"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-07-2475"},{"issue":"246","key":"e_1_2_7_20_1","first-page":"1","article-title":"2000 CDC Growth charts for the United States: methods and development. National Center for Health Statistics","volume":"11","author":"Kuczmarski RJ","year":"2002","journal-title":"Vital Health Stat"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24178"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpbc.26833","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.26833","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T15:26:35Z","timestamp":1696001195000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.26833"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,8]]},"references-count":20,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1002\/pbc.26833"],"URL":"https:\/\/doi.org\/10.1002\/pbc.26833","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,8]]},"article-number":"e26833"}}