{"title":"高风险弥漫性大b细胞淋巴瘤高剂量甲氨蝶呤预防后延迟甲氨蝶呤消除。","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":"{\"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}","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
摘要
目的大剂量甲氨蝶呤（HD-MTX）广泛应用于中枢神经系统（CNS）复发风险高的弥漫大b细胞淋巴瘤（DLBCL）患者。确保以最小的不良事件安全预防给药是一个关键问题；然而，很少有研究详细说明HD-MTX预防高危DLBCL患者的安全性。我们分析了该人群中与HD-MTX相关的不良事件，重点是延迟MTX消除。方法：本多中心回顾性研究纳入了2014年至2020年期间接受HD-MTX一线治疗的98例中枢神经系统复发高风险DLBCL患者。中枢神经系统预防包括2个周期的HD-MTX (3.0 g/m2)，间隔2周。结果诊断时的中位年龄为63（34-84）岁，34例患者接受减剂量甲氨蝶呤（MTX）治疗。MTX延迟消除的总发生率为18.4%。在接受3小时MTX输注组（n=50）中未观察到MTX延迟消除的病例。MTX延迟消除患者的毒性反应发生率高于未消除患者（77.8% vs. 26.2%, p≤0.05），包括≥3级不良事件和≤2级肾功能障碍的发生率较高。结论甲氨蝶呤延迟消除与并发症增加有关。较短的甲氨蝶呤输注速率，特别是在3小时，可以降低甲氨蝶呤延迟消除的风险。
Delayed Methotrexate Elimination Following High-dose Methotrexate Prophylaxis in High-risk Diffuse Large B-cell Lymphoma.
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.
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