CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Managing Infection Complications in the Setting of Chimeric Antigen Receptor T cell (CAR-T) Therapy.
Managing Infection Complications in the Setting of Chimeric Antigen Receptor T cell (CAR-T) Therapy.
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CAR-T 细胞(CAR-T 细胞)疗法改变了非霍奇金淋巴瘤(NHL)和多发性骨髓瘤的管理模式。感染并发症已成为值得关注的问题,可能在治疗期间发生并导致发病和死亡。本综述将感染并发症分为三类:输注前期(从淋巴清除治疗前至第 0 天)、早期(输注日至输注后第 30 天)和晚期(输注后第 30 天起)。输注前期感染与既往化疗及桥接治疗密切相关;早期感染更可能与淋巴清除化疗及预期短暂的 3–4 级中性粒细胞减少有关。晚期感染尤其令人担忧,因为其与不良风险特征相关,包括持续性中性粒细胞减少、淋巴细胞减少、低丙种球蛋白血症和 B 细胞缺失所致的体液免疫及适应性免疫失调。此阶段可能发生细菌感染、呼吸道及其他病毒感染、原虫感染和真菌感染。
我们建议加强支持治疗,包括及时识别并使用生长因子支持治疗中性粒细胞减少,在适当情况下对特定病毒开展监测检测,酌情补充治疗低丙种球蛋白血症,并对风险较高者(如使用大剂量类固醇或存在持续性血细胞减少者)延长抗菌药物预防。
最后,建议根据美国疾病控制与预防中心(CDC)和移植指南,在 CAR-T 治疗后对患者重新进行免疫接种。
Chimeric antigen receptor T-cell (CAR T-cell) therapy has changed the paradigm of management of non-Hodgkin's lymphoma (NHL) and Multiple Myeloma. Infection complications have emerged as a concern that can arise in the setting of therapy and lead to morbidity and mortality. In this review, we classified infection complications into three categories, pre-infusion phase from the time pre- lymphodepletion (LD) up to day zero, early phase from day of infusion to day 30 post-infusion, and late phase after day 30 onwards.
Infections arising in the pre-infusion phase are closely related to previous chemotherapy and bridging therapy. Infections arising in the early phase are more likely related to LD chemo and the expected brief period of grade 3-4 neutropenia.
Infections arising in the late phase are particularly worrisome because they are associated with adverse risk features including prolonged neutropenia, dysregulation of humoral and adaptive immunity with lymphopenia, hypogammaglobinemia, and B cell aplasia. Bacterial, respiratory and other viral infections, protozoal and fungal infections can occur during this time .
We recommend enhanced supportive care including prompt recognition and treatment of neutropenia with growth factor support, surveillance testing for specific viruses in the appropriate instance, management of hypogammaglobulinemia with repletion as appropriate and extended antimicrobial prophylaxis in those at higher risk (e. g. high dose steroid use and prolonged cytopenia).
Finally, we recommend re-immunizing patients post CAR-T based on CDC and transplant guidelines.
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