{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T10:18:48Z","timestamp":1780049928915,"version":"3.53.1"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,3,3]],"date-time":"2024-03-03T00:00:00Z","timestamp":1709424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82003742"],"award-info":[{"award-number":["82003742"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>This study delivers a comprehensive evaluation of the efficacy and pharmacokinetics of high\u2010dose methotrexate (HDMTX) in a large cohort of Chinese paediatric acute lymphoblastic leukaemia patients. A total of 533 patients were included in the prognostic analysis. An association was observed between lower steady\u2010state MTX concentrations (&lt;56\u2009\u03bcmol\/L) and poorer outcomes in intermediate\u2010\/high\u2010risk (IR\/HR) patients. Subgroup analysis further revealed that this relationship between concentrations and prognosis was even more pronounced in patients with <jats:italic>MLL<\/jats:italic> rearrangements. In contrast, such an association did not emerge within the low\u2010risk patient group. Additionally, utilizing population pharmacokinetic modelling (6051 concentrations from 815 patients), we identified the significant impact of physiological maturation, estimated glomerular filtration rate, sex and concurrent dasatinib administration on MTX pharmacokinetics. Simulation\u2010based recommendations include a reduced dosage regimen for those with renal insufficiency and a specific 200\u2009mg\/kg dosage for infants under 1\u2009year. The findings underscore the critical role of HDMTX in treating IR\/HR populations and call for a reassessment of its application in lower\u2010risk groups. An individualized pharmacokinetic dosage regimen could achieve the most optimal results, ensuring the largest proportion of steady\u2010state concentrations within the optimal range.<\/jats:p>","DOI":"10.1111\/bjh.19365","type":"journal-article","created":{"date-parts":[[2024,3,3]],"date-time":"2024-03-03T23:58:20Z","timestamp":1709510300000},"page":"1354-1366","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["High\u2010dose methotrexate pharmacokinetics and its impact on prognosis of paediatric acute lymphoblastic leukaemia patients: A population pharmacokinetic study"],"prefix":"10.1111","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9099-1588","authenticated-orcid":false,"given":"Xiaoxiao","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Hematology\/Oncology, Shanghai Children's Medical Center, School of Medicine Shanghai Jiao Tong University  Shanghai 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