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血液系统恶性肿瘤 CAR T 细胞治疗后的细胞因子释放综合征和神经毒性。

Cytokine release syndrome and neurotoxicity following CAR T-cell therapy for hematologic malignancies.

机构信息

Department of Pharmacy, Hospital of the University of Pennsylvania, Philadelphia, Pa.

Division of Cellular Therapy and Stem Cell Transplant, Hospital of the University of Pennsylvania, Philadelphia, Pa; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa.

出版信息

J Allergy Clin Immunol. 2020 Nov;146(5):940-948. doi: 10.1016/j.jaci.2020.07.025. Epub 2020 Aug 6.


DOI:10.1016/j.jaci.2020.07.025
PMID:32771558
Abstract

Chimeric antigen receptor T cells are a new and exciting immunotherapeutic approach to managing cancer, with impressive efficacy but potentially life-threatening inflammatory toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Patients with severe CRS may develop capillary leak syndrome and disseminated intravascular coagulation, with a cytokine signature similar to that of macrophage activation syndrome/hemophagocytic lymphohistiocytosis. Moderate-to-severe CRS is managed with the IL-6 receptor antagonist tocilizumab with or without corticosteroids, with questions remaining regarding the optimal management of nonresponders. ICANS is an inflammatory neurotoxicity typically occurring after CRS and characterized by impaired blood-brain barrier integrity. Symptoms of encephalopathy range from mild confusion and aphasia to somnolence, obtundation, and in some cases seizures and cerebral edema. ICANS is currently managed with corticosteroids; however, the optimal dose and duration remain to be determined. Little information is available to guide the management of patients with steroid-refractory ICANS. Numerous cytokine-targeted therapies have been proposed to manage these inflammatory toxicities, but few clinical data are available. Management of inflammatory toxicities of chimeric antigen receptor T cells often requires multidisciplinary management and intensive care, during which allergists and immunologists may encounter patients with these unique toxicities.

摘要

嵌合抗原受体 T 细胞是一种用于癌症治疗的新型免疫疗法,具有显著疗效,但也可能导致危及生命的炎症毒性,如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)。严重 CRS 患者可能会发生毛细血管渗漏综合征和弥散性血管内凝血,细胞因子特征与巨噬细胞活化综合征/噬血细胞性淋巴组织细胞增多症相似。中重度 CRS 采用白细胞介素-6 受体拮抗剂托珠单抗联合或不联合皮质类固醇治疗,对于无应答者的最佳治疗方法仍存在疑问。ICANS 是一种炎症性神经毒性,通常在 CRS 之后发生,其特征是血脑屏障完整性受损。脑病症状从轻度意识模糊和失语到嗜睡、昏迷,在某些情况下还会出现癫痫发作和脑水肿。ICANS 目前采用皮质类固醇治疗;然而,最佳剂量和持续时间仍有待确定。对于类固醇难治性 ICANS 患者,几乎没有信息可用于指导其管理。已经提出了许多细胞因子靶向疗法来治疗这些炎症毒性,但很少有临床数据。嵌合抗原受体 T 细胞的炎症毒性的管理通常需要多学科管理和重症监护,在此期间,过敏症专家和免疫学家可能会遇到这些具有独特毒性的患者。

相似文献

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Cytokine release syndrome and neurotoxicity following CAR T-cell therapy for hematologic malignancies.

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[4]
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[6]
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[10]
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