当前位置: X-MOL 学术J. Allergy Clin. Immunol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Cytokine release syndrome and neurotoxicity following CAR T-cell therapy for hematologic malignancies.
Journal of Allergy and Clinical Immunology ( IF 14.2 ) Pub Date : 2020-08-06 , DOI: 10.1016/j.jaci.2020.07.025
Craig W Freyer 1 , David L Porter 2
Affiliation  

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.



中文翻译:

CAR T细胞疗法治疗血液系统恶性肿瘤后的细胞因子释放综合征和神经毒性。

嵌合抗原受体T细胞是一种新型且令人兴奋的免疫疗法,用于治疗癌症,具有令人印象深刻的功效,但潜在的威胁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的神经毒性综合征(ICANS)。患有严重CRS的患者可能会出现毛细血管渗漏综合征和弥散性血管内凝血,其细胞因子特征类似于巨噬细胞激活综合征/嗜血淋巴细胞组织细胞增生症。中度至重度CRS可以通过IL-6受体拮抗剂Tocilizumab进行或不进行皮质类固醇治疗,但对于无反应者的最佳治疗仍存在疑问。ICANS是一种炎症性神经毒性,通常在CRS后发生,其特征是血脑屏障完整性受损。脑病的症状范围从轻度神志不清和失语症到嗜睡,肥胖和某些情况下的癫痫发作和脑水肿。ICANS目前使用皮质类固醇治疗;但是,最佳剂量和持续时间有待确定。几乎没有信息可指导类固醇难治性ICANS患者的治疗。已经提出了许多靶向细胞因子的疗法来控制这些炎性毒性,但是很少有临床数据可用。嵌合抗原受体T细胞的炎症毒性的管理通常需要多学科的管理和重症监护,在此期间过敏症患者和免疫学家可能会遇到具有这些独特毒性的患者。ICANS目前使用皮质类固醇治疗;但是,最佳剂量和持续时间有待确定。几乎没有信息可指导类固醇难治性ICANS患者的治疗。已经提出了许多靶向细胞因子的疗法来控制这些炎性毒性,但是很少有临床数据可用。嵌合抗原受体T细胞的炎症毒性的管理通常需要多学科的管理和重症监护,在此期间过敏症患者和免疫学家可能会遇到具有这些独特毒性的患者。ICANS目前使用皮质类固醇治疗;但是,最佳剂量和持续时间有待确定。几乎没有信息可指导类固醇难治性ICANS患者的治疗。已经提出了许多靶向细胞因子的疗法来控制这些炎性毒性,但是很少有临床数据可用。嵌合抗原受体T细胞的炎症毒性的管理通常需要多学科的管理和重症监护,在此期间过敏症患者和免疫学家可能会遇到具有这些独特毒性的患者。但几乎没有临床数据。嵌合抗原受体T细胞的炎症毒性的管理通常需要多学科的管理和重症监护,在此期间过敏症患者和免疫学家可能会遇到具有这些独特毒性的患者。但几乎没有临床数据。嵌合抗原受体T细胞的炎症毒性的管理通常需要多学科的管理和重症监护,在此期间过敏症患者和免疫学家可能会遇到具有这些独特毒性的患者。

更新日期:2020-08-06
down
wechat
bug