Student's Scientific Association at the Department of Pediatric Hematology, Oncology and Transplantation, Medical University of Lublin, A. Racławickie 1, 20-059 Lublin, Poland.
Student Scientific Society, Laboratory of Genetic Diagnostics, Medical University of Lublin, A. Racławickie 1, 20-059 Lublin, Poland.
Int J Mol Sci. 2022 May 15;23(10):5515. doi: 10.3390/ijms23105515.
Immunotherapy is a milestone in the treatment of poor-prognosis pediatric acute lymphoblastic leukemia (ALL) and is expected to improve treatment outcomes and reduce doses of conventional chemotherapy without compromising the effectiveness of the therapy. However, both chemotherapy and immunotherapy cause side effects, including neurological ones. Acute neurological complications occur in 3.6-11% of children treated for ALL. The most neurotoxical chemotherapeutics are L-asparaginase (L-ASP), methotrexate (MTX), vincristine (VCR), and nelarabine (Ara-G). Neurotoxicity associated with methotrexate (MTX-NT) occurs in 3-7% of children treated for ALL and is characterized by seizures, stroke-like symptoms, speech disturbances, and encephalopathy. Recent studies indicate that specific polymorphisms in genes related to neurogenesis may have a predisposition to MTX toxicity. One of the most common complications associated with CAR T-cell therapy is immune effector cell-associated neurotoxicity syndrome (ICANS). Mechanisms of neurotoxicity in CAR T-cell therapy are still unknown and may be due to disruption of the blood-brain barrier and the effects of elevated cytokine levels on the central nervous system (CNS). In this review, we present an analysis of the current knowledge on the mechanisms of neurotoxicity of standard chemotherapy and the targeted therapy in children with ALL.
免疫疗法是治疗预后不良的小儿急性淋巴细胞白血病（ALL）的一个里程碑，有望改善治疗效果并减少常规化疗剂量，同时不影响治疗效果。然而，化疗和免疫疗法都会引起副作用，包括神经方面的副作用。在接受 ALL 治疗的儿童中，有 3.6-11%会发生急性神经并发症。最具神经毒性的化疗药物有 L-天冬酰胺酶（L-ASP）、甲氨蝶呤（MTX）、长春新碱（VCR）和阿糖胞苷（Ara-G）。与甲氨蝶呤（MTX-NT）相关的神经毒性发生在接受 ALL 治疗的儿童中 3-7%，其特征为癫痫发作、类似中风的症状、言语障碍和脑病。最近的研究表明，与神经发生相关的基因中的特定多态性可能导致 MTX 毒性易感性。与 CAR T 细胞疗法相关的最常见并发症之一是免疫效应细胞相关神经毒性综合征（ICANS）。CAR T 细胞疗法引起神经毒性的机制尚不清楚，可能是由于血脑屏障的破坏和细胞因子水平升高对中枢神经系统（CNS）的影响所致。在这篇综述中，我们对标准化疗和儿童 ALL 靶向治疗的神经毒性机制的现有知识进行了分析。
