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:Infections and CAR-T cells for the treatment of lymphoid malignancies: a narrative review.
Infections and CAR-T cells for the treatment of lymphoid malignancies: a narrative review.
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CAR-T(CAR-T)细胞的应用彻底改变了淋巴系统恶性肿瘤患者的治疗模式。然而,感染并发症是CAR-T 相关常见不良事件,可能成为治疗成功的重要障碍。感染发生率呈双相模式:CAR-T 细胞输注后前30天感染增加,30天后则出现迟发感染。
总体而言,治疗早期以细菌感染为主,长期阶段则转为病毒或机会性感染;CAR-T 治疗后侵袭性真菌感染较少见。感染相关危险因素包括宿主因素(如基础恶性肿瘤和既往治疗)以及治疗因素[CAR-T 产品、细胞因子释放综合征(CRS)、免疫效应细胞相关神经毒性综合征(ICANS)、免疫效应细胞相关血液毒性(ICAHT)和低丙种球蛋白血症]。对于接受CAR-T 治疗的患者,仔细关注感染体征和症状是优化管理的必要条件;降低感染风险的策略具有重要临床意义,因为这些患者超过一半的非复发死亡归因于感染。本综述总结淋巴系统恶性肿瘤患者接受CAR-T 细胞治疗后的感染并发症现有认识,为读者提供改善管理和预防策略的工具。
The use of chimeric antigen receptor-T (CAR-T) cells have revolutionized the therapeutic paradigm of patients with lymphoid malignancies.
However, infectious complications represent a frequent CAR-T cell-related adverse event, potentially being a major hurdle for the successful outcome of the patients. The infection incidence follows a biphasic pattern, with "early" infections rising during the first 30 days after CAR-T cells infusion, and "late" infections from day 30 onward.
Overall, bacterial infections prevail in the early phase after therapy, with a switch to viral or opportunistic infections in the long-term period, while invasive fungal infections are rare events after CAR-T therapy. Risk factors associated with infectious complications include host-related factors such as the underlying malignancy and previous treatments, and treatment-related factors [CAR-T cell product, cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), immune effector cell-associated hematotoxicity (ICAHT), hypogammaglobulinemia].
Careful attention to signs and symptoms of infections is mandatory for an optimal management of patients undergoing CAR-T therapy, and strategies to mitigate infectious risk are clinically relevant: indeed, over half of non-relapse mortality in these patients is attributed to infections. In the present review we attempt to summarize the current knowledge on infectious complications occurring in patients receiving CAR-T cell therapy for lymphoid malignancies in order to provide the readers tools for better management and prevention strategies.
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