Masuda Yasutaka, Nara Katsuhiko, Fujii-Mori Alice, Shimura Arika, Taoka Kazuki, Watadani Takeyuki, Morita Ken, Yamamoto Takehito, Kurokawa Mineo, Takada Tappei
Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Pharmacy, The University of Tokyo Hospital, Tokyo, Japan.
Ann Hematol. 2025 Feb;104(2):1095-1104. doi: 10.1007/s00277-024-05989-1. Epub 2024 Sep 13.
Neurotoxicity associated with high-dose chemotherapy and whole brain radiotherapy (WBRT) is one of major complications for patients with central nervous system lymphoma (CNSL). Here we determined the incidence and risk factors of treatment-related leukoencephalopathy (tLE) in a clinical setting. We retrospectively reviewed clinical and radiological findings of 126 patients with (CNSL) treated with high-dose methotrexate with or without intrathecal methotrexate administration (IT MTX) and response-adapted WBRT. During the whole observation period with a median of 38.7 months, tLE was found in 33 patients, most of them asymptomatic, with the median time to development 3.0 months, and the cumulative incidence reaching 29.2% (95% confidence interval, 20.6-38.2%) two years post chemotherapy. By multivariable analysis, IT MTX was identified as the only one significant risk factor (hazard ratio, 4.50; P < 0.001), and the number of IT MTX was associated with the increased incidence and severity of tLE. These findings highlight the frequent neurological complications associated with CNS-directed therapy and confirm the neurotoxicity of IT MTX.
与大剂量化疗和全脑放疗（WBRT）相关的神经毒性是中枢神经系统淋巴瘤（CNSL）患者的主要并发症之一。在此，我们在临床环境中确定了治疗相关白质脑病（tLE）的发生率和危险因素。我们回顾性分析了126例接受大剂量甲氨蝶呤治疗（伴或不伴鞘内注射甲氨蝶呤（IT MTX））以及适应性WBRT的CNSL患者的临床和影像学检查结果。在中位时间为38.7个月的整个观察期内，33例患者发现了tLE，其中大多数无症状，发病的中位时间为3.0个月，化疗后两年的累积发生率达到29.2%（95%置信区间，20.6-38.2%）。通过多变量分析，IT MTX被确定为唯一的显著危险因素（风险比，4.50；P < 0.001），且IT MTX的次数与tLE的发生率和严重程度增加相关。这些发现突出了与中枢神经系统定向治疗相关的常见神经并发症，并证实了IT MTX的神经毒性。
