Nagai Yusa, Hayakawa Itaru, Sugawa Masahiro, Gocho Yoshihiro, Sakaguchi Hirotoshi, Tomizawa Daisuke, Abe Yuichi
Division of Neurology, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan.
Division of Neurology, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan.
Pediatr Neurol. 2025 Jun;167:77-81. doi: 10.1016/j.pediatrneurol.2025.03.010. Epub 2025 Mar 22.
Chimeric antigen receptor T-cell (CAR-T) therapy for hematological malignancies causes a neurological complication known as immune effector cell-associated neurotoxicity syndrome (ICANS). The precise neurocognitive pathology underlying ICANS remains incompletely described. The aim of this study is to elucidate that persistent cognitive dysfunction as potential neurotoxicity of CAR-T therapy.
This was a single-center consecutive study of ICANS caused by CAR-T therapy for B-cell acute lymphoblastic leukemia. We determined the cognitive functions of all patients with ICANS at the onset of ICANS symptoms and followed them up in the neurology department thereafter.
Among the 10 CAR-T cases between 2020 and 2022, three patients had ICANS. None of the patients experienced seizures. Of the three patients, the preadolescent patient showed decreased levels of consciousness, tremors, and striatal signs without cognitive dysfunction. The other two adolescent and young adult patients presented with cognitive decline, short- and long-term memory loss, and emotional disturbances. Although the Immune Effector Cell-Associated Encephalopathy score remained low, the cognitive impairment was profound and disabling in both cases. The neurological status of all patients fully recovered to pre-CAR-T status within one month.
The findings in our cases indicate that persistent cognitive dysfunction may be a potentially under-recognized outcome of neurotoxicity due to CAR-T therapy for B-cell acute lymphoblastic leukemia in adolescents and young adults. Detailed neuropsychologic assessments may be beneficial for CAR-T therapy.
嵌合抗原受体T细胞（CAR-T）疗法用于治疗血液系统恶性肿瘤时会引发一种神经并发症，称为免疫效应细胞相关神经毒性综合征（ICANS）。ICANS潜在的精确神经认知病理学仍未得到充分描述。本研究的目的是阐明持续性认知功能障碍是CAR-T疗法潜在的神经毒性。
这是一项针对CAR-T疗法治疗B细胞急性淋巴细胞白血病所致ICANS的单中心连续性研究。我们在ICANS症状出现时测定了所有ICANS患者的认知功能，并随后在神经科对他们进行随访。
在2020年至2022年期间的10例CAR-T病例中，3例患者发生了ICANS。所有患者均未出现癫痫发作。在这3例患者中，青春期前患者出现意识水平下降、震颤和纹状体体征，但无认知功能障碍。另外两名青少年和青年成人患者出现认知衰退、短期和长期记忆丧失以及情绪障碍。尽管免疫效应细胞相关脑病评分仍然较低，但这两例患者的认知障碍都很严重且致残。所有患者的神经状态在1个月内完全恢复到CAR-T治疗前的状态。
我们病例中的研究结果表明，持续性认知功能障碍可能是CAR-T疗法治疗青少年和青年成人B细胞急性淋巴细胞白血病所致神经毒性中一个潜在未被充分认识的结果。详细的神经心理学评估可能对CAR-T疗法有益。
