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嵌合抗原受体 T 细胞治疗后感染并发症、免疫重建和感染预防。

Infectious complications, immune reconstitution, and infection prophylaxis after CD19 chimeric antigen receptor T-cell therapy.

机构信息

Division of Hematology and Research Unit in Translational Hematology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

出版信息

Bone Marrow Transplant. 2022 Oct;57(10):1477-1488. doi: 10.1038/s41409-022-01756-w. Epub 2022 Jul 15.

Abstract

CD19-targeted chimeric antigen receptor (CAR) T-cell becomes a breakthrough therapy providing excellent remission rates and durable disease control for patients with relapsed/refractory (R/R) hematologic malignancies. However, CAR T-cells have several potential side effects including cytokine release syndrome, neurotoxicities, cytopenia, and hypogammaglobulinemia. Infection has been increasingly recognized as a complication of CAR T-cell therapy. Several factors predispose CAR T-cell recipients to infection. Fortunately, although studies show a high incidence of infection post-CAR T-cells, most infections are manageable. In contrast to patients who undergo hematopoietic stem cell transplant, less is known about post-CAR T-cell immune reconstitution. Therefore, evidence regarding antimicrobial prophylaxis and vaccination strategies in these patients is more limited. As CAR T-cell therapy becomes the standard treatment for R/R B lymphoid malignancies, we should expect a larger impact of infections in these patients and the need for increased clinical attention. Studies exploring infection and immune reconstitution after CAR T-cell therapy are clinically relevant and will provide us with a better understanding of the dynamics of immune function after CAR T-cell therapy including insights into appropriate strategies for prophylaxis and treatment of infections in these patients. In this review, we describe infections in recipients of CAR T-cells, and discuss risk factors and potential mitigation strategies.

摘要

嵌合抗原受体(CAR)T 细胞针对 CD19 成为突破性治疗方法,为复发/难治性(R/R)血液系统恶性肿瘤患者提供了极好的缓解率和持久的疾病控制。然而,CAR T 细胞有几个潜在的副作用,包括细胞因子释放综合征、神经毒性、血细胞减少和低丙种球蛋白血症。感染已越来越被认为是 CAR T 细胞治疗的一种并发症。有几个因素使 CAR T 细胞受者容易感染。幸运的是,尽管研究表明 CAR T 细胞后感染的发生率很高,但大多数感染是可以控制的。与接受造血干细胞移植的患者相比,人们对 CAR T 细胞后免疫重建的了解较少。因此,关于这些患者的抗菌预防和疫苗接种策略的证据更有限。随着 CAR T 细胞疗法成为 R/R B 淋巴细胞恶性肿瘤的标准治疗方法,我们应该预计这些患者的感染会产生更大的影响,需要增加临床关注。探索 CAR T 细胞治疗后感染和免疫重建的研究具有临床相关性,将使我们更好地了解 CAR T 细胞治疗后免疫功能的动态,包括了解针对这些患者感染的适当预防和治疗策略。在这篇综述中,我们描述了 CAR T 细胞受者的感染,并讨论了风险因素和潜在的缓解策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c77/9285870/3f5290003747/41409_2022_1756_Fig1_HTML.jpg

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