{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T20:08:40Z","timestamp":1777147720071,"version":"3.51.4"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,6,10]],"date-time":"2020-06-10T00:00:00Z","timestamp":1591747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["PB\u2010PG\u20101207\u201015250"],"award-info":[{"award-number":["PB\u2010PG\u20101207\u201015250"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["eJHaem"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although survival rates for pediatric acute lymphoblastic leukemia are now excellent, this is at the expense of prolonged chemotherapy regimens. We report the long\u2010term immune effects in children treated according to the UK Medical Research Council UKALL 2003 protocol. Peripheral blood lymphocyte subsets and immunoglobulin levels were studied in 116 participants, at six time points, during and for 18\u2010month following treatment, with 30\u201039 patients analyzed at each time point.<\/jats:p><jats:p>Total lymphocytes were reduced during maintenance chemotherapy and remained low 18\u00a0months following treatment completion. CD4 T\u00a0cells remained significantly reduced 18\u00a0months after treatment, but CD8\u00a0cells and natural killer cells recovered to normal values. The fall in na\u00efve B\u2010cell numbers during maintenance was most marked, but numbers recovered rapidly after cessation of treatment. Memory B\u00a0cells, particularly nonclass\u2010switched memory B\u00a0cells, remained below normal levels 18\u00a0months following treatment. All immunoglobulin subclasses were reduced during treatment compared to normal values, with IgM levels most affected.<\/jats:p><jats:p>This study demonstrates that immune reconstitution differs between lymphocyte compartments. Although total B\u2010cell numbers recover rapidly, disruption of memory\/na\u00efve balance persists and T\u2010cell compartment persist at 18\u00a0months. This highlights the impact of modern chemotherapy regimens on immunity, and thus, infectious susceptibility and response to immunization.<\/jats:p>","DOI":"10.1002\/jha2.27","type":"journal-article","created":{"date-parts":[[2020,6,10]],"date-time":"2020-06-10T19:14:33Z","timestamp":1591816473000},"page":"142-151","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Immune reconstitution in children following chemotherapy for acute leukemia"],"prefix":"10.1002","volume":"1","author":[{"given":"Anthony P.","family":"Williams","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Institute for Life Sciences University of Southampton  Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Bate","sequence":"additional","affiliation":[{"name":"NIHR Southampton Clinical Research Facility NIHR Southampton Biomedical Research Centre and Southampton NIHR CRUK Experimental Cancer Medicine Centre University Hospital Southampton NHS Foundation Trust  Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachael","family":"Brooks","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Institute for Life Sciences University of Southampton  Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Chisholm","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology Royal Marsden Hospital  Sutton Surrey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart C.","family":"Clarke","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Institute for Life Sciences University of Southampton  Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Dixon","sequence":"additional","affiliation":[{"name":"Southampton Clinical Trials Unit  Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saul N.","family":"Faust","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Institute for Life Sciences University of Southampton  Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angeliki","family":"Galanopoulou","sequence":"additional","affiliation":[{"name":"Southampton Clinical Trials Unit  Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul T.","family":"Heath","sequence":"additional","affiliation":[{"name":"Paediatric Infectious Diseases Research Group &amp; Vaccine Institute St. George's University of London and St. Georges University Hospitals NHS Trust  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Maishman","sequence":"additional","affiliation":[{"name":"Southampton Clinical Trials Unit  Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Mapstone","sequence":"additional","affiliation":[{"name":"NIHR Southampton Clinical Research Facility NIHR Southampton Biomedical Research Centre and Southampton NIHR CRUK Experimental Cancer Medicine Centre University Hospital Southampton NHS Foundation Trust  Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soonie R.","family":"Patel","sequence":"additional","affiliation":[{"name":"Paediatric Department Croydon University Hospital  Croydon UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajay","family":"Vora","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology Great Ormond Street Hospital  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sam A.","family":"Wilding","sequence":"additional","affiliation":[{"name":"Southampton Clinical Trials Unit  Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5652-4722","authenticated-orcid":false,"given":"Juliet C.","family":"Gray","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Institute for Life Sciences University of Southampton  Southampton UK"},{"name":"NIHR Southampton Clinical Research Facility NIHR Southampton Biomedical Research Centre and Southampton NIHR CRUK Experimental Cancer Medicine Centre University Hospital Southampton NHS Foundation Trust  Southampton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,6,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.59.1636"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1400972"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(17)30052-2"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70600-9"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21327"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19920315)69:6<1481::AID-CNCR2820690628>3.0.CO;2-L"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3109\/08880019409141671"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2009.07862.x"},{"issue":"2","key":"e_1_2_8_10_1","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1111\/j.1365-2141.2010.08478.x","article-title":"Immune reconstitution in children following chemotherapy for haematological malignancies: a long\u2010term follow\u2010up","volume":"152","author":"Tilburg CM","year":"2011","journal-title":"Br J Haematol"},{"issue":"4","key":"e_1_2_8_11_1","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.leukres.2010.10.005","article-title":"Reduced versus intensive chemotherapy for childhood acute lymphoblastic leukemia: impact on lymphocyte compartment composition","volume":"35","author":"Tilburg CM","year":"2011","journal-title":"Leuk Res"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00043426-200411000-00008"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.26047"},{"issue":"6","key":"e_1_2_8_14_1","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0301-0546(03)79203-9","article-title":"Humoral immunity in pediatric patients with acute lymphoblastic leukaemia","volume":"31","author":"Martin Ibanez I","year":"2003","journal-title":"Allergol Immunopathol (Madr)"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2013.816423"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404326"},{"issue":"1","key":"e_1_2_8_17_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.17219\/acem\/37030","article-title":"The recovery of immune system parameters in children following lymphoblastic leukemia therapy: preliminary report","volume":"23","author":"Pietras W","year":"2014","journal-title":"Adv Clin Exp Med"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12253-008-9073-5"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1086\/511636"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22415"},{"key":"e_1_2_8_21_1","first-page":"ciz965","article-title":"13\u2010valent pneumococcal conjugate vaccine in children with acute lymphoblastic leukaemia: protective immunity can be achieved on completion of treatment","author":"Bate J","year":"2019","journal-title":"Clin Infect Dis"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70243-8"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2012.02671.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2011.02609.x"},{"key":"e_1_2_8_25_1","volume-title":"PRU Handbook of Clinical Immunochemistry","author":"Milford WA","year":"2004"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-03-560847"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2007.07.002"},{"issue":"5","key":"e_1_2_8_28_1","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1111\/j.1365-2141.2010.08148.x","article-title":"Systematic review of the addition of vincristine plus steroid pulses in maintenance treatment for childhood acute lymphoblastic leukaemia\u2014an individual patient data meta\u2010analysis involving 5,659 children","volume":"149","author":"Eden T","year":"2010","journal-title":"Br J Haematol"},{"issue":"4","key":"e_1_2_8_29_1","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1111\/j.1365-2141.2010.08463.x","article-title":"Impact of reduced chemotherapy treatment for good risk childhood acute lymphoblastic leukaemia on infectious morbidity*","volume":"152","author":"Tilburg CM","year":"2011","journal-title":"Br J Haematol"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2007.06601.x"}],"container-title":["eJHaem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjha2.27","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jha2.27","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jha2.27","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jha2.27","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T05:17:57Z","timestamp":1693891077000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jha2.27"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,10]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1002\/jha2.27"],"URL":"https:\/\/doi.org\/10.1002\/jha2.27","archive":["Portico"],"relation":{},"ISSN":["2688-6146","2688-6146"],"issn-type":[{"value":"2688-6146","type":"print"},{"value":"2688-6146","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,10]]},"assertion":[{"value":"2020-04-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}