{"title":"Delayed Methotrexate Elimination Following High-dose Methotrexate Prophylaxis in High-risk Diffuse Large B-cell Lymphoma.","authors":"Masahiro Akimoto, Takuya Miyazaki, Hiroyuki Takahashi, Takaaki Takeda, Yuto Hibino, Mayumi Tokunaga, Takuma Ohashi, Ayako Matsumura, Haruka Teshigawara, Taisei Suzuki, Hiroshi Teranaka, Yuki Nakajima, Kenji Matsumoto, Chizuko Hashimoto, Katsumichi Fujimaki, Hiroyuki Fujita, Rika Sakai, Shin Fujisawa, Hideaki Nakajima","doi":"10.2169/internalmedicine.4999-24","DOIUrl":null,"url":null,"abstract":"<p><p>Objective High-dose methotrexate (HD-MTX) is widely used as central nervous system (CNS) prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL) who are at a high risk of CNS relapse. Ensuring safe prophylactic administration with minimal adverse events is a key concern; however, few studies have detailed the safety profile of HD-MTX prophylaxis in patients with high-risk DLBCL. We analyzed the adverse events associated with HD-MTX in this population, focusing on delayed MTX elimination. Methods This multicenter retrospective study included 98 patients with DLBCL at high risk of CNS relapse who received HD-MTX as part of frontline therapy between 2014 and 2020. CNS prophylaxis involved 2 cycles of HD-MTX (3.0 g/m<sup>2</sup>) at 2-week intervals. Results The median age at the diagnosis was 63 (34-84) years old, and 34 patients received a reduced methotrexate (MTX) dose. The overall incidence of delayed MTX elimination was 18.4%. No cases of delayed MTX elimination were observed in the group that received a 3-h MTX infusion (n=50). Toxicities were more frequent in patients with delayed MTX elimination than in those without (77.8% vs. 26.2%, p≤0.05), including higher incidences of grade ≥3 adverse events and grade ≤2 renal dysfunction. Conclusion Delayed MTX elimination is associated with increased complications. Shorter MTX infusion rates, particularly at 3 h, may reduce the risk of delayed MTX elimination.</p>","PeriodicalId":13719,"journal":{"name":"Internal Medicine","volume":" ","pages":"2716-2722"},"PeriodicalIF":1.1000,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Internal Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2169/internalmedicine.4999-24","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/15 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
Abstract
Objective High-dose methotrexate (HD-MTX) is widely used as central nervous system (CNS) prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL) who are at a high risk of CNS relapse. Ensuring safe prophylactic administration with minimal adverse events is a key concern; however, few studies have detailed the safety profile of HD-MTX prophylaxis in patients with high-risk DLBCL. We analyzed the adverse events associated with HD-MTX in this population, focusing on delayed MTX elimination. Methods This multicenter retrospective study included 98 patients with DLBCL at high risk of CNS relapse who received HD-MTX as part of frontline therapy between 2014 and 2020. CNS prophylaxis involved 2 cycles of HD-MTX (3.0 g/m2) at 2-week intervals. Results The median age at the diagnosis was 63 (34-84) years old, and 34 patients received a reduced methotrexate (MTX) dose. The overall incidence of delayed MTX elimination was 18.4%. No cases of delayed MTX elimination were observed in the group that received a 3-h MTX infusion (n=50). Toxicities were more frequent in patients with delayed MTX elimination than in those without (77.8% vs. 26.2%, p≤0.05), including higher incidences of grade ≥3 adverse events and grade ≤2 renal dysfunction. Conclusion Delayed MTX elimination is associated with increased complications. Shorter MTX infusion rates, particularly at 3 h, may reduce the risk of delayed MTX elimination.
期刊介绍:
Internal Medicine is an open-access online only journal published monthly by the Japanese Society of Internal Medicine.
Articles must be prepared in accordance with "The Uniform Requirements for Manuscripts Submitted to Biomedical Journals (see Annals of Internal Medicine 108: 258-265, 1988), must be contributed solely to the Internal Medicine, and become the property of the Japanese Society of Internal Medicine. Statements contained therein are the responsibility of the author(s). The Society reserves copyright and renewal on all published material and such material may not be reproduced in any form without the written permission of the Society.