背景:嵌合抗原受体(CAR)-T细胞疗法彻底改变了急性淋巴细胞白血病的治疗,非霍奇金淋巴瘤,和多发性骨髓瘤,但以独特的毒性为代价,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,和长期的“靶向肿瘤外”效应。
方法:所有这些因素都会增加已经高度免疫受损的患者人群的感染风险。的确,感染性并发症是CAR-T细胞术后非复发死亡率的关键决定因素.这些风险因素的时间分布形成了CAR-T细胞输注后早期与晚期的不同感染模式。此外,由于其靶标在不同分化阶段的B谱系细胞上的表达,CD19和B细胞成熟抗原(BCMA)CAR-T细胞诱导不同的免疫缺陷,可能需要不同的预防策略。感染发生率在输注后的第一个月期间最高,随后下降。然而,即使在输液一年后,感染仍然相对常见。
结果:CD19后早期细菌感染占主导地位,而在BCMACAR-T细胞治疗后,细菌和病毒病因之间的分布更加平等。真菌感染普遍罕见。巨细胞病毒(CMV)和其他疱疹病毒的报道越来越多,但是是否有必要对所有人进行例行监测,或患者的一个亚组,还有待确定。不同中心的临床实践差异很大,许多不确定性仍然存在,包括CMV监测,抗菌和抗真菌预防和持续时间,使用免疫球蛋白替代疗法,接种疫苗的时间。
结论:风险分层工具可用,可能有助于区分输液后发热的感染性和非感染性原因,并预测严重感染。这些工具需要前瞻性验证,它们在临床实践中的整合需要系统的研究。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.