{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:22:25Z","timestamp":1791393745222,"version":"4.3.3"},"reference-count":36,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BTG Pharmaceuticals"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cancers"],"abstract":"<jats:p>Objectives: To determine the incidence of delayed methotrexate elimination (DME) and acute kidney injury (AKI) and their associations with clinical outcomes in patients receiving high-dose methotrexate (HDMTX) for cancer treatment. Methods: The HDMTX European Registry collected medical records data from 12 institutions in 5 European countries to investigate the clinical practice patterns of healthcare providers utilizing HDMTX for cancer treatment. Cancer types included were acute lymphoblastic leukemia (ALL), primary central nervous system lymphoma (PCNSL), non-Hodgkin lymphoma (NHL), osteosarcoma, and other CNS cancers. Primary endpoints were the incidence of DME and AKI; secondary endpoints were clinical outcomes, including hospital length of stay (LOS), delay in the subsequent course of treatment, methotrexate dose reduction, and omission of next course of treatment. Associations between the primary and secondary endpoints were analyzed with Chi-square and Wilcoxon rank-sum tests. Results: Among the 2501 total HDMTX courses analyzed, DME occurred in 302 courses (12.1%), and AKI in 384 courses (15.4%). DME incidence was highest in courses for PCNSL (18.2%) and NHL (17.2%); AKI incidence was highest in ALL courses (21.0%). Incidence of DME and AKI varied by age and methotrexate infusion duration among the different cancer types. Occurrence of DME was associated with longer delays prior to the next course of treatment, longer hospital LOS, and more frequent methotrexate dose reductions and dose omissions. Conclusions: While HDMTX is a very effective and safe treatment, administration of efficacious doses of methotrexate can lead to AKI and DME, and no single or combination of patient or treatment factors was found to reliably predict their occurrence. Thus, diligent monitoring of methotrexate levels is imperative for early detection and prompt management of nephrotoxicity in all settings where HDMTX treatment is administered.<\/jats:p>","DOI":"10.3390\/cancers18010124","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T13:30:52Z","timestamp":1767187852000},"page":"124","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["High-Dose Methotrexate at All Ages: Safety, Efficacy, and Outcomes from the HDMTX European Registry"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2388-3518","authenticated-orcid":false,"given":"Bertrand","family":"Pourroy","sequence":"first","affiliation":[{"name":"Oncopharma Unit, H\u00f4pitaux Universitaires de Marseille La Timone, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7584-924X","authenticated-orcid":false,"given":"Maria D.","family":"Aumente","sequence":"additional","affiliation":[{"name":"Pharmacy Service, Reina Sofia University Hospital, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7025-1735","authenticated-orcid":false,"given":"Christian","family":"Koenecke","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, University of Hannover, 30167 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3834-0727","authenticated-orcid":false,"given":"Martin","family":"Stanulla","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, University of Hannover, 30167 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9606-6124","authenticated-orcid":false,"given":"Andr\u00e9s J. M.","family":"Ferreri","sequence":"additional","affiliation":[{"name":"Lymphoma Unit, IRCCS San Raffaele Scientific Institute, 20132 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8659-1603","authenticated-orcid":false,"given":"Thais","family":"Murciano-Carillo","sequence":"additional","affiliation":[{"name":"Pediatric Oncology & Hematology, Hospital Universitari Vall d\u2019Hebron, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8444-6007","authenticated-orcid":false,"given":"Madhumita","family":"Dandapani","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Oncology\/Haematology, University of Nottingham, Nottingham NG5 1PB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4438-6588","authenticated-orcid":false,"given":"Timothy A.","family":"Ritzmann","sequence":"additional","affiliation":[{"name":"Children\u2019s Brain Tumour Research Centre, University of Nottingham, Nottingham NG7 2UH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7076-7969","authenticated-orcid":false,"given":"Pere","family":"Barba","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Universitari Vall d\u2019Hebron, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7740-9096","authenticated-orcid":false,"given":"Etienne","family":"Chatelut","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institut Universitaire du Cancer-Oncopole, 31059 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1806-2686","authenticated-orcid":false,"given":"Katrina 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