甲氨蝶呤 (MTX) 虽然是当代儿童急性淋巴细胞白血病 (ALL)/淋巴瘤 (LBL) 治疗方案中不可或缺的一部分，可改善预后，但可能会导致严重的神经毒性，并产生长期后果。 MTX 诱导的神经毒性的发病机制、诱发因素和治疗方法尚未明确。我们研究的目的是检测大群接受统一方案治疗的儿科 ALL/LBL 患者中 MTX 诱导的神经毒性的发生率、危险因素并评估总体结果。我们对 2018 年 1 月至 2022 年 12 月期间诊断为 ALL 和 LBL 的 622 名连续儿童（≤ 14 岁）的病历进行了回顾性审计，并在特里凡得琅地区癌症中心儿科肿瘤科接受修改后的 BFM-95 方案治疗。使用二元逻辑回归分析确定了诱发 MTX 诱导神经毒性的危险因素。 43名儿童被诊断为MTX神经毒性，发生率为6.9%。其中超过三分之二患有高级别 MTX 诱导的神经毒性 CTCAE v5.0，中位年龄为 9 岁（范围：9 个月至 14 岁）。近一半的患者在方案 M 期间出现 MTX 神经毒性，随后进行 Ib 期巩固（15%）。这些患者中的大多数（84%，36/43）再次接受 MTX 治疗，其中 11%（4/36）出现复发。在最后一次随访中，15% 的人有持续的神经功能缺损。单变量分析发现年龄较大（年龄 > 5 岁）（p < 0.001）、T细胞表型（p = 0.040）、诱导期间的肿瘤溶解综合征（p < 0.001）、MTX暴露前的基线肾脏问题（p < 0.001）和中枢神经系统白血病受累 (p<0.003) 与 MTX 神经毒性显着相关。在多变量分析中，年龄较大（>5岁）、诱导过程中的肿瘤溶解和中枢神经系统白血病保留了统计显着性（p<0.05）。在儿童急性淋巴细胞白血病/淋巴瘤治疗过程中，甲氨蝶呤引起的神经毒性在大多数情况下是一种短暂现象，重新使用 MTX 通常是安全的。在诱导过程中发生肿瘤溶解和中枢神经系统白血病受累的年龄较大儿童在 ALL/LBL 治疗期间发生 MTX 诱导的神经毒性的风险增加。© 2024 英国血液学会和 John Wiley

Methotrexate (MTX), although an indispensable part of contemporary treatment protocols for childhood acute lymphoblastic leukaemia (ALL)/lymphomas (LBL) in improving outcomes, can lead to serious neurotoxicity with long-term consequences. The aetiopathogenesis, predisposing factors and treatment for MTX-induced neurotoxicity are not yet well defined. The aim of our study was to detect the incidence, risk factors and to assess the overall outcomes of MTX-induced neurotoxicity among large cohort of paediatric ALL/LBL patients treated on a uniform protocol. We conducted retrospective audit of medical records of 622 consecutive children (≤14 years) diagnosed with ALL and LBL between January 2018 and December 2022 and treated on modified BFM-95 protocol at the Department of Pediatric Oncology, Regional Cancer Centre, Thiruvananthapuram. Risk factors predisposing to MTX-induced neurotoxicity were identified using binary logistic regression analysis. Forty-three children were diagnosed with MTX-induced neurotoxicity with an incidence rate of 6.9%. More than two-thirds of them had high-grade MTX-induced neurotoxicity CTCAE v5.0 with a median age of 9 years (range: 9 months to 14 years). Almost half of them developed MTX neurotoxicity during Protocol M followed by Phase-Ib consolidation (15%). Majority of these patients (84%, 36/43) were challenged again with MTX, with 11% (4/36) developing recurrence. Fifteen per cent had persistent neurological deficits at last follow-up. Univariate analysis found older age (age > 5 years) (p < 0.001), T-cell phenotype (p = 0.040), tumour lysis syndrome during induction (p < 0.001), baseline renal problems prior to MTX exposure (p < 0.001) and CNS leukaemic involvement (p < 0.003) to be significantly associated with MTX neurotoxicity. On multivariate analysis, older age (>5 years), tumour lysis during induction and CNS leukaemia retained statistical significance (p < 0.05). Methotrexate-induced neurotoxicity during paediatric acute lymphoblastic leukaemia/lymphoma therapy is a transient phenomenon in majority and re-challenge with MTX is generally safe. Older age children who develop tumour lysis during induction and CNS leukaemic involvement are at increased risk for MTX-induced neurotoxicity during ALL/LBL treatment.© 2024 British Society for Haematology and John Wiley & Sons Ltd.