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多中心应用治疗性血浆置换治疗CAR-T疗法后对皮质类固醇/托珠单抗难治性细胞因子释放综合征的经验。

Multi-centers experience using therapeutic plasma exchange for corticosteroid/tocilizumab-refractory cytokine release syndrome following CAR-T therapy.

作者信息

Pu Yedi, Zhao Yifan, Qi Yuekun, Liu Yang, Zhang Meng, Xiao Xia, Lyu Hairong, Meng Juanxia, Zhu Haibo, Xu Kailin, Han Weidong, Zhao Mingfeng

机构信息

Department of Hematology, Tianjin First Central Hospital, Tianjin 300380, China.

The First Central Clinical College of Tianjin Medical University, Tianjin 300380, China.

出版信息

Int Immunopharmacol. 2024 Mar 30;130:111761. doi: 10.1016/j.intimp.2024.111761. Epub 2024 Feb 28.

Abstract

The chimeric antigen receptor T (CAR-T) cell therapy significantly enhances the prognosis of various hematologic malignancies; however, the systemic expansion of CAR-T cells also gives rise to severe cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). Despite the successful application of corticosteroids and tocilizumab in alleviating severe CRS in most patients, there are still individuals who experience life-threatening CRS without responding to the aforementioned therapies. In our retrospective cohort, we conducted an analysis of clinical and laboratory parameters, including inflammatory cytokines, in 17 patients from three centers who underwent therapeutic plasma exchange (TPE) for refractory CRS with or without ICANS following CAR-T products treatment. Our findings demonstrate a significant improvement in both clinical symptoms and laboratory parameters subsequent to TPE treatment. The rapid decrease in temperature and levels of inflammatory indexes indicates the remarkable scavenging efficacy of TPE against cytokine storm following CAR-T therapy. In conclusion, TPE may serve as a valuable and safe adjunct to corticosteroids and tocilizumab in the management of severe CRS resulting from CAR-T cell infusion. We eagerly await further prospective studies to validate this finding.

摘要

嵌合抗原受体T(CAR-T)细胞疗法显著改善了各种血液系统恶性肿瘤的预后;然而,CAR-T细胞的全身扩增也会引发严重的细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)。尽管皮质类固醇和托珠单抗成功应用于缓解大多数患者的严重CRS,但仍有个体出现危及生命的CRS且对上述治疗无反应。在我们的回顾性队列研究中,我们对来自三个中心的17例患者进行了临床和实验室参数分析,包括炎症细胞因子,这些患者在接受CAR-T产品治疗后因难治性CRS伴或不伴ICANS接受了治疗性血浆置换(TPE)。我们的研究结果表明,TPE治疗后临床症状和实验室参数均有显著改善。体温和炎症指标水平的快速下降表明TPE对CAR-T治疗后细胞因子风暴具有显著的清除效果。总之,在管理CAR-T细胞输注引起的严重CRS方面,TPE可能是皮质类固醇和托珠单抗的一种有价值且安全的辅助治疗方法。我们热切期待进一步的前瞻性研究来验证这一发现。

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