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This retrospective study showed a higher incidence of MTX neurotoxicity (11.3%) with the classic presentations of stroke\u2010like syndrome (17\/19), seizures (2\/19), and the majority (14\/19) showing characteristic radiographic findings. Most cases occurred during the consolidation phase, a median of 6\u00a0days after MTX exposure. Older age, Hispanic ethnicity, greater body mass index, and National Cancer Institute high\u2010risk status were predictors of neurotoxicity, with only ethnicity remaining significant in adjusted analyses. Prophylactic leucovorin after repeated intrathecal MTX doses may be protective.<\/jats:p>","DOI":"10.1002\/pbc.70000","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T05:08:06Z","timestamp":1763442486000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Retrospective Study to Identify Demographic and Clinical Risk Factors for the Development of Methotrexate\u2010Associated Neurotoxicity in Children and Young Adults With Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1979-3947","authenticated-orcid":false,"given":"Cassandra","family":"Grello","sequence":"first","affiliation":[{"name":"Department of Pediatrics New York Presbyterian\u2010Weill Cornell  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Demecillo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics NYU Langone Health  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristyn","family":"Pierce","sequence":"additional","affiliation":[{"name":"Department of Pediatrics NYU Langone Health  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylwia","family":"Jasinski","sequence":"additional","affiliation":[{"name":"Department of Pediatrics NYU Langone Health  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8547-1658","authenticated-orcid":false,"given":"Elizabeth","family":"Raetz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics NYU Langone Health  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis Andrew De Los","family":"Reyes","sequence":"additional","affiliation":[{"name":"Department of Pediatrics NYU Langone Health  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.37.8018"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.30585"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2009.05.002"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.01692"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.53.0808"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.328"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25850"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-018-2525-0"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/hematology.2021000269"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.268565"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.920214"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.19559"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199403033300907"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00043426-200406000-00011"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000069773"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2014.01.048"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/08880010290057336"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30035-3"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.34646"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-0939"}],"container-title":["Pediatric Blood &amp; 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