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嵌合抗原受体 (CAR) T 细胞疗法的感染性并发症。

Infectious complications of chimeric antigen receptor (CAR) T-cell therapies.

机构信息

Division of Clinical Research, NIAID, Bethesda, MD; NIH Clinical Center, Bethesda, MD.

出版信息

Semin Hematol. 2023 Jan;60(1):52-58. doi: 10.1053/j.seminhematol.2023.02.003. Epub 2023 Mar 6.

Abstract

CAR T-cells have revolutionized the treatment of many hematological malignancies. Thousands of patients with lymphoma, acute lymphoblastic leukemia, and multiple myeloma have received this "living medicine" and achieved durable remissions. Their place in therapy continues to evolve, and there is ongoing development of new generation CAR constructs, CAR T-cells against solid tumors and CAR T-cells against chronic infections like human immunodeficiency virus and hepatitis B. A significant fraction of CAR T-cell recipients, unfortunately, develop infections. This is in part due to factors intrinsic to the patient, but also to the treatment, which requires lymphodepletion (LD), causes neutropenia and hypogammaglobulinemia and necessarily increases the state of immunosuppression of the patient. The goal of this review is to present the infectious complications of CAR T-cell therapy, explain their temporal course and risk factors, and provide recommendations for their prevention, diagnosis, and management.

摘要

嵌合抗原受体 T 细胞(CAR T 细胞)疗法已经彻底改变了许多血液系统恶性肿瘤的治疗方式。数以千计的淋巴瘤、急性淋巴细胞白血病和多发性骨髓瘤患者已经接受了这种“活的药物”,并获得了持久的缓解。这种疗法的地位仍在不断发展,新一代的 CAR 结构、针对实体瘤的 CAR T 细胞和针对慢性感染(如人类免疫缺陷病毒和乙型肝炎)的 CAR T 细胞正在不断发展。不幸的是,相当一部分 CAR T 细胞接受者会发生感染。这部分是由于患者自身的固有因素,但也与治疗有关,该治疗需要淋巴细胞耗竭(LD),导致中性粒细胞减少和低丙种球蛋白血症,并必然增加患者的免疫抑制状态。本文的目的是介绍 CAR T 细胞治疗的感染并发症,解释其时间过程和危险因素,并提供预防、诊断和管理的建议。

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