{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:45:22Z","timestamp":1792802722969,"version":"4.5.0"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003243","name":"Ministerstvo Zdravotnictv\u00ed Cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["AZV NU21\u201003\u201000411"],"award-info":[{"award-number":["AZV NU21\u201003\u201000411"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The randomized, multicenter, prospective Phase 3 trial (NCT02777736) evaluated central nervous system (CNS) prophylaxis using either intravenous (i.v.) or intrathecal (i.t.) methotrexate (MTX) in diffuse large B\u2010cell lymphoma (DLBCL). Treatment consisted of six cycles of R\u2010CHOP\u00a0+\u00a02xR or DA\u2010EPOCH\u2010R\u00a0+\u00a02xR. Patients with intermediate or high\u2010risk CNS International Prognostic Index (CNS\u2010IPI) were randomized to receive CNS prophylaxis with either 2 doses of MTX 3\u00a0g\/m\n                    <jats:sup>2<\/jats:sup>\n                    i.v. (arm A) or 6 doses of MTX 12\u00a0mg i.t. (arm B). Patients with low\u2010risk CNS\u2010IPI did not receive MTX prophylaxis (arm C). The primary objective was to compare the cumulative incidence of CNS relapse between arms A and B. Secondary objectives included evaluation of overall response rate (ORR), complete remission rate (CRR), progression\u2010free survival (PFS), overall survival (OS), and treatment\u2010related safety across all arms. Between 7\/2015 and 5\/2024, a total of 100 patients were enrolled: 30 in arm A, 31 in arm B, and 39 in arm C. ORR did not differ among arms (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.20). During a median follow\u2010up of 54.9\u00a0months, CNS relapses were observed in three patients who had received MTX prophylaxis\u2010one in arm A and two in arm B. The 5\u2010year cumulative incidence of CNS relapse was 0% in arm A and 8.7% in arm B (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.72). However, due to the small sample size, the primary endpoint results are inconclusive. Median PFS was comparable between arms A and B (HR 0.66,\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.20). MTX i.v. was associated with a significantly higher grade \u2265\u00a03 neutropenia (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0003) and infection (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0063). The higher infection rate contributed to a worse 5\u2010year OS in arm A versus B (47.2% vs. 72.4%, HR 0.46,\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.04). Conclusion: our trial faced limitations due to a low number of randomized participants, making the interpretation of results challenging. A larger, international randomized trial is necessary to determine the benefit of CNS prophylaxis.\n                  <\/jats:p>","DOI":"10.1002\/hon.70193","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T01:44:26Z","timestamp":1777599866000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Efficacy and Toxicity of CNS Prophylaxis in Diffuse Large B\u2010Cell Lymphoma (CLSG\u2010CNS\u201001): A Randomized, Multicenter, Prospective Phase 3 Trial"],"prefix":"10.1002","volume":"44","author":[{"given":"H.","family":"Mocikova","sequence":"first","affiliation":[{"name":"Department of Haematology Fakultni Nemocnice Kralovske Vinohrady and Third Faculty of Medicine Charles University  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Gaherova","sequence":"additional","affiliation":[{"name":"Department of Haematology Fakultni Nemocnice Kralovske Vinohrady and Third Faculty of Medicine Charles University  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Jancarkova","sequence":"additional","affiliation":[{"name":"Department of Haematology Fakultni Nemocnice Kralovske Vinohrady and Third Faculty of Medicine Charles University  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Suri","sequence":"additional","affiliation":[{"name":"Department of Haematology Fakultni Nemocnice Kralovske Vinohrady and Third Faculty of Medicine Charles University  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Janikova","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Hematology and Oncology University Hospital Brno Faculty of Medicine Masaryk University  Brno Czech 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Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Duras","sequence":"additional","affiliation":[{"name":"Department of Hemato\u2010Oncology University Hospital and Faculty of Medicine  Ostrava Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Trnkova","sequence":"additional","affiliation":[{"name":"I<sup>st<\/sup> Department of Medicine General University Hospital I<sup>st<\/sup> Faculty of Medicine Charles University  Prague Czech Republic"},{"name":"Datacenter of the Czech Lymphoma Study Group  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Blahovcova","sequence":"additional","affiliation":[{"name":"Datacenter of the Czech Lymphoma Study Group  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Kozak","sequence":"additional","affiliation":[{"name":"Department of Haematology Fakultni Nemocnice 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