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血液系统恶性肿瘤嵌合抗原受体(CAR)-T 细胞治疗后的感染

英文原题:Infections after chimeric antigen receptor (CAR)-T-cell therapy for hematologic malignancies.

查看英文原题

Infections after chimeric antigen receptor (CAR)-T-cell therapy for hematologic malignancies.

PubMed 2023/10/03(内容时间) Transpl Infect Dis Q2 · IF 2.5(JCR 2025)

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研究概要

风险分层工具已可用,可能有助于区分输注后发热的感染性与非感染性原因,并预测严重感染。

中文摘要

嵌合抗原受体(CAR)T细胞疗法改变了急性淋巴细胞白血病、非霍奇金淋巴瘤和多发性骨髓瘤的治疗,但也会带来独特毒性,包括细胞因子释放综合征、免疫效应细胞相关神经毒性综合征及长期“靶向肿瘤、同时影响正常组织”效应。

上述因素会进一步增加本已严重免疫受损患者的感染风险。事实上,感染并发症是CAR-T 治疗后非复发死亡的主要决定因素。感染风险因素随时间的分布,导致CAR-T 输注后早期和晚期出现不同感染模式。此外,由于CD19和B细胞成熟抗原(BCMA)靶点分别表达于B细胞谱系不同分化阶段的细胞上,CD19和BCMA CAR-T 会引起不同的免疫缺陷,可能需要不同的预防策略。输注后首月感染发生率最高,之后逐渐降低,但输注一年后感染仍相对常见。

CD19 CAR-T 后早期以细菌感染为主;BCMA CAR-T 后细菌和病毒感染分布较为均衡;真菌感染在两类治疗后均少见。巨细胞病毒(CMV)及其他疱疹病毒感染的报告日益增多,但是否需要对所有患者或特定亚组常规监测仍待明确。各中心临床实践差异很大,CMV监测、抗菌和抗真菌预防措施及疗程、免疫球蛋白替代治疗的应用和疫苗接种时机等方面仍存在不确定性。

现有风险分层工具可能有助于区分输注后发热的感染性和非感染性原因,并预测重度感染,但仍需前瞻性验证,并系统研究其临床应用方式。

展开英文摘要原文

Chimeric antigen receptor (CAR)-T-cell therapies have revolutionized the management of acute lymphoblastic leukemia, non-Hodgkin lymphoma, and multiple myeloma but come at the price of unique toxicities, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and long-term "on-target off-tumor" effects.

All of these factors increase infection risk in an already highly immunocompromised patient population. Indeed, infectious complications represent the key determinant of non-relapse mortality after CAR-T cells. The temporal distribution of these risk factors shapes different infection patterns early versus late post-CAR-T-cell infusion. Furthermore, due to the expression of their targets on B lineage cells at different stages of differentiation, CD19, and B-cell maturation antigen (BCMA) CAR-T cells induce distinct immune deficits that could require different prevention strategies. Infection incidence is the highest during the first month post-infusion and subsequently decreases thereafter. However, infections remain relatively common even a year after infusion.

Bacterial infections predominate early after CD19, while a more equal distribution between bacterial and viral causes is seen after BCMA CAR-T-cell therapy, and fungal infections are universally rare. Cytomegalovirus (CMV) and other herpesviruses are increasingly breported, but whether routine monitoring is warranted for all, or a subgroup of patients, remains to be determined. Clinical practices vary substantially between centers, and many areas of uncertainty remain, including CMV monitoring, antibacterial and antifungal prophylaxis and duration, use of immunoglobulin replacement therapy, and timing of vaccination.

Risk stratification tools are available and may help distinguish between infectious and non-infectious causes of fever post-infusion and predict severe infections. These tools need prospective validation, and their integration in clinical practice needs to be systematically studied.

论文信息

作者
Kampouri E、Little JS、Rejeski K、Manuel O、Hammond SP、Hill JA
单位
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.United States
文献类型
综述
期刊
Transplant infectious disease : an official journal of the Transplantation Society2023 Nov
原文标识
PubMed 37787373 · DOI 10.1111/tid.14157