{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:46:12Z","timestamp":1792802772203,"version":"4.5.0"},"reference-count":41,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"24","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,8,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>In large B-cell lymphoma (LBCL), use of high-dose methotrexate (HD-MTX) to prevent CNS relapse (so-called CNS prophylaxis) remains controversial. International guidelines continue to recommend HD-MTX in patients deemed ultra high risk (UHR) because of a lack of robust data specific to these subgroups. This study was designed to examine the impact of HD-MTX specifically in UHR patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Data from two previous retrospective analyses were combined to produce a cohort of UHR patients (\u22651 of the following criteria: CNS international prognostic index score 5-6; testicular, renal\/adrenal, or breast involvement; \u22653 extranodal sites), treated with or without HD-MTX. The primary outcome was CNS relapse rate (isolated or concurrent with systemic relapse) measured from diagnosis with additional landmark analysis of all responding patients with no progression event at 6 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Analyses were performed on 1,923 patients meeting UHR criteria. No significant difference in 3-year CNS relapse rate was observed between no HD-MTX (n = 1,051) versus HD-MTX patients (n = 872), including in multivariable analyses adjusting for baseline characteristics (3-year rate, 9.3%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      8.1%; adjusted hazard ratio [HR], 1.13 [95% CI, 0.82 to 1.57]). Analyses restricted to isolated CNS relapse also confirmed no difference (5.9%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      5.7%; adjusted HR, 1.03 [95% CI, 0.69 to 1.53]). In the landmark analysis (no HD-MTX n = 782, HD-MTX n = 773), no difference in 3-year CNS relapse was observed (6.7%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      6.6%, adjusted HR, 0.95 [95% CI, 0.62 to 1.44]).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>To our knowledge, this is the largest international comparative data set of patients with LBCL with UHR features showing no significant reduction in CNS relapse with HD-MTX in all UHR or in any individual subgroup. Despite inherent limitations of retrospective analyses, the data strongly support previous studies in suggesting HD-MTX prophylaxis has no meaningful benefit for most patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-26-00947","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T14:55:09Z","timestamp":1781189709000},"page":"2290-2302","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":3,"title":["High-Dose Methotrexate as CNS Prophylaxis in Ultra High-Risk Large B-Cell Lymphoma: An International Multicenter Analysis"],"prefix":"10.1200","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5423-3270","authenticated-orcid":false,"given":"Matthew R.","family":"Wilson","sequence":"first","affiliation":[{"name":"Beatson West of Scotland Cancer Centre, Glasgow, United 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