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早期鞘内注射地塞米松可有效缓解免疫效应细胞相关神经毒性综合征。

Earlier intrathecal dexamethasone effectively alleviate immune effector cell-associated neurotoxicity syndrome.

机构信息

Hematology & Oncology, Children's Hospital of Soochow University, Suzhou 215000, Jiangsu, China.

Pediatric Intensive Care Unit, Children's Hospital of Soochow University, Suzhou 215000, Jiangsu, China.

出版信息

Int Immunopharmacol. 2024 Dec 5;142(Pt B):113214. doi: 10.1016/j.intimp.2024.113214. Epub 2024 Sep 24.

Abstract

Chimeric antigen receptor T cell (CAR-T) therapy is effective in treating relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). However, the side effects of immune effector cell-associated neurotoxicity syndrome (ICANS) remain a problem. The current frontline therapies for ICANS include steroids and supportive care. For the steroid-refractory and severe ICANS, several studies have reported excellent efficacy of intrathecal (IT) corticosteroids alone or in combination with chemotherapy. However, whether patients can benefit from IT dexamethasone (dex) before grade 3 or refractory ICANS remains unclear. In this study, the patients with ICANS (≥1) after CAR-T cell therapy were assigned to the IT group and non-IT group. Clinical information, laboratory parameters, and serum cytokine levels were analyzed. A significant and rapid reduction in inflammatory cytokines and biomarkers was observed after 24 h of IT dex treatment. With IT dex, 83.3 % (15/18) of patients recovered from neurotoxicity. Moreover, this option significantly shortens the recovery time of ICANS without affecting the efficacy of CAR-T cell therapy. Earlier initiation of IT dex is the optimal management of ICANS resulting from CAR-T cell therapy, but larger sample studies are needed to determine its efficacy in these settings.

摘要

嵌合抗原受体 T 细胞(CAR-T)疗法在治疗复发/难治性 B 细胞急性淋巴细胞白血病(R/R B-ALL)方面非常有效。然而,免疫效应细胞相关神经毒性综合征(ICANS)的副作用仍然是一个问题。目前,ICANS 的一线治疗包括皮质类固醇和支持性护理。对于皮质类固醇难治性和严重的 ICANS,几项研究报告了鞘内(IT)皮质类固醇单独或联合化疗的极好疗效。然而,在出现 3 级或难治性 ICANS 之前,患者是否能从 IT 地塞米松(dex)中获益尚不清楚。在这项研究中,CAR-T 细胞治疗后出现 ICANS(≥1)的患者被分配到 IT 组和非-IT 组。分析了临床信息、实验室参数和血清细胞因子水平。在 IT 地塞米松治疗 24 小时后,观察到炎症细胞因子和生物标志物显著且迅速降低。使用 IT 地塞米松,83.3%(15/18)的患者从神经毒性中恢复。此外,这种选择显著缩短了 ICANS 的恢复时间,而不影响 CAR-T 细胞治疗的疗效。早期开始 IT 地塞米松是治疗 CAR-T 细胞治疗引起的 ICANS 的最佳方法,但需要更大的样本研究来确定其在这些情况下的疗效。

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