Although methotrexate (MTX) is the most widely used therapy for central nervous system (CNS) prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL), the optimal regimen remains unclear. We examined the efficacy of different prophylactic regimens in 585 patients with newly diagnosed DLBCL and high-risk for CNS relapse, treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens from 2001 to 2017, of whom 295 (50%) received prophylaxis. Intrathecal (IT) MTX was given to 253 (86%) and high-dose MTX (HD-MTX) to 42 (14%). After a median follow-up of 6.8 years, 36 of 585 patients relapsed in the CNS, of whom 14 had received prophylaxis. The CNS relapse risk at 1 year was lower for patients who received prophylaxis than patients who did not: 2% vs. 7.1%. However, the difference became less significant over time (5-year risk 5.6% vs. 7.5%), indicating prophylaxis tended to delay CNS relapse rather than prevent it. Furthermore, the CNS relapse risk was similar in patients who received IT and HD-MTX (5-year risk 5.6% vs. 5.2%). Collectively, our data indicate the benefit of MTX for CNS prophylaxis is transient, highlighting the need for more effective prophylactic regimens. In addition, our results failed to demonstrate a clinical advantage for the HD-MTX regimen.

尽管甲氨蝶呤 (MTX) 是弥漫性大 B 细胞淋巴瘤 (DLBCL) 患者中枢神经系统 (CNS) 预防最广泛使用的疗法，但最佳治疗方案仍不清楚。我们检查了 585 名新诊断的 DLBCL 和 CNS 复发高风险患者的不同预防方案的疗效，这些患者从 2001 年到 2001 年至2017 年，其中 295 人（50%）接受了预防治疗。 253 名患者 (86%) 接受鞘内 (IT) MTX 治疗，42 名患者 (14%) 接受高剂量 MTX (HD-MTX) 治疗。中位随访 6.8 年后，585 名患者中有 36 名中枢神经系统复发，其中 14 人接受了预防治疗。接受预防治疗的患者 1 年 CNS 复发风险低于未接受预防治疗的患者：2% vs. 7.1%。然而，随着时间的推移，差异变得不那么显着（5 年风险分别为 5.6% 和 7.5%），这表明预防往往会推迟而不是预防 CNS 复发。此外，接受 IT 和 HD-MTX 治疗的患者中枢神经系统复发风险相似（5 年风险分别为 5.6% 和 5.2%）。总的来说，我们的数据表明 MTX 对 CNS 预防的益处是短暂的，这凸显了对更有效的预防方案的需求。此外，我们的结果未能证明 HD-MTX 方案的临床优势。