{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:07:24Z","timestamp":1790856444193,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T00:00:00Z","timestamp":1723766400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007403","name":"Dagmar Marshalls Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007403","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006197","name":"Fonden til L\u00e6gevidenskabens Fremme","doi-asserted-by":"publisher","award":["20\u2010L\u20100251"],"award-info":[{"award-number":["20\u2010L\u20100251"]}],"id":[{"id":"10.13039\/501100006197","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010733","name":"B\u00f8rnecancerfonden","doi-asserted-by":"publisher","award":["2018\u20103703"],"award-info":[{"award-number":["2018\u20103703"]}],"id":[{"id":"10.13039\/100010733","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010733","name":"B\u00f8rnecancerfonden","doi-asserted-by":"publisher","award":["2020\u20106745"],"award-info":[{"award-number":["2020\u20106745"]}],"id":[{"id":"10.13039\/100010733","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Severe intestinal mucositis (IM) increases the risk of bloodstream infections (BSI) and inflammatory toxicity during acute lymphoblastic leukaemia (ALL) induction treatment. However, the implications of IM in subsequent ALL therapy phases after achieving remission remain unknown. This study investigated the relationship between IM (measured by plasma citrulline and the chemokine CCL20) and the development of BSI and systemic inflammation (reflected by C\u2010reactive protein, CRP) in children with ALL during high\u2010dose methotrexate (HDMTX) treatment, an important part of ALL consolidation therapy. The study compared patients treated according to the NOPHO ALL 2008 protocol (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200952) and the ALLTogether1 protocol (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200942), both with identical HDMTX procedures but different scheduling. One week post\u2010HDMTX, citrulline dropped to median levels of 14.5 and 16.9\u2009\u03bcM for patients treated according to the NOPHO ALL 2008 and ALLTogether1 protocols, respectively (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.11). In a protocol and neutrophil count\u2010adjusted analysis, hypocitrullinaemia (&lt;10\u2009\u03bcmol\/L) was associated with increased odds of BSI within 3\u2009weeks from HDMTX (OR\u2009=\u200926.2,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0074). Patients treated according to the NOPHO ALL 2008 protocol exhibited increased mucosal\u2010 and systemic inflammation post\u2010HDMTX compared to patients treated according to ALLTogether1, with increased CCL20 (14.6 vs. 3.7\u2009pg\/mL,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001) and CRP levels (10.0 vs. 1.0\u2009mg\/L, p\u2009&lt;\u20090.0001). Both citrulline and CCL20 correlated with CRP for these patients (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>s<\/jats:italic>\n                    <\/jats:sub>\n                    \u2009=\u2009\u22120.44,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0016 and\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>s<\/jats:italic>\n                    <\/jats:sub>\n                    \u2009=\u20090.35,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.016, respectively). These results suggest that hypocitrullinaemia following HDMTX increases the risk of BSI, confirming previous observations from more intensive treatments. Moreover, these data indicate that the patients' vulnerability to mucositis and inflammatory toxicity after chemotherapy varies with treatment protocol.\n                  <\/jats:p>","DOI":"10.1002\/ijc.35136","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T10:18:45Z","timestamp":1723803525000},"page":"164-173","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Intestinal mucositis, systemic inflammation and bloodstream infections following high\u2010dose methotrexate treatment in childhood acute lymphoblastic leukaemia: Comparison between the\n                    <scp>NOPHO ALL<\/scp>\n                    2008 protocol and the\n                    <scp>ALLTogether1<\/scp>\n                    protocol"],"prefix":"10.1002","volume":"156","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2364-4445","authenticated-orcid":false,"given":"Sarah","family":"Weischendorff","sequence":"first","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Rigshospitalet Copenhagen University Hospital  Copenhagen Denmark"},{"name":"Institute for Inflammation Research, Centre for Rheumatology and Spine Disease, Rigshospitalet Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3750-8556","authenticated-orcid":false,"given":"Silvia","family":"de Pietri","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Rigshospitalet Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Rathe","sequence":"additional","affiliation":[{"name":"Hans Christian Andersen Children's Hospital Odense University Hospital  Odense Denmark"},{"name":"Department of Clinical Research University of Southern Denmark  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjeld","family":"Schmiegelow","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Rigshospitalet Copenhagen University Hospital  Copenhagen Denmark"},{"name":"Institute of Clinical Medicine University of Copenhagen"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas Leth","family":"Frandsen","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Rigshospitalet Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malene Johanne","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Rigshospitalet Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Weimann","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Rigshospitalet Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus Henrik","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Institute for Inflammation Research, Centre for Rheumatology and Spine Disease, Rigshospitalet Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Enevold","sequence":"additional","affiliation":[{"name":"Institute for Inflammation Research, Centre for Rheumatology and Spine Disease, Rigshospitalet Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helin Berna","family":"Kocadag","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Rigshospitalet Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"Moser","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Rigshospitalet Copenhagen University Hospital  Copenhagen Denmark"},{"name":"Department of Immunology and Microbiology Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Rigshospitalet Copenhagen University Hospital  Copenhagen Denmark"},{"name":"Institute for Inflammation Research, Centre for Rheumatology and Spine Disease, Rigshospitalet Copenhagen University Hospital  Copenhagen Denmark"},{"name":"Institute of Clinical Medicine University of Copenhagen"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1400972"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.59.1636"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.247031"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2019.1605071"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12562"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.13962"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32942"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.28793"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1017\/ice.2014.38"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.18668"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2016.06.002"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-021-06199-5"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3109\/08880019609030842"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2008.01468.x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3109\/08880018.2015.1034819"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.5414\/CPP46584"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.34639"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015156"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13113"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/tid.12195"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2008.170"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-022-01719-1"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/2050640617737632"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22210"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:JOCI.0000018066.46279.6b"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjx145"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389200220666190130161758"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2022.2074987"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2015-0164"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.757464"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.265"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-023-02077-7"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/SPC.0000000000000339"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCO.0000000000000180"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24119592"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.10768.1"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064918"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2014.12.038"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2009.10.036"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/SPC.0000000000000701"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1704563"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.35136","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T07:20:44Z","timestamp":1731482444000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.35136"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,16]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/ijc.35136"],"URL":"https:\/\/doi.org\/10.1002\/ijc.35136","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,16]]},"assertion":[{"value":"2024-03-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}