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急性髓系白血病 CLL1 CAR-T 细胞治疗后感染性并发症的分布

英文原题:Infectious complications distribution following CLL1 CAR-T cell therapy for acute myeloid leukemiass.

查看英文原题

Infectious complications distribution following CLL1 CAR-T cell therapy for acute myeloid leukemiass.

PubMed 2025/03/15(内容时间) Cancer Immunol Immunother Q1 · IF 5.8(JCR 2025)

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中文摘要

靶向CLL1的CAR-T(CAR-T)细胞疗法为难治性或复发性急性髓系白血病(AML)提供了一种新的治疗途径。CLL1 CAR-T 疗法靶向清除肿瘤细胞的同时也会对中性粒细胞产生细胞毒性作用,导致严重的中性粒细胞减少,从而显著增加CAR-T 治疗期间感染并发症的风险。

然而,与这一策略相关的感染并发症尚未得到全面研究。本研究旨在评估51例接受CLL1 CAR-T 细胞输注的患者队列中28天内感染并发症的发生率。

同时,采用单因素和多因素分析探讨CLL1 CAR-T 治疗期间感染并发症的危险因素。研究共观察到51例患者中32例(63%)发生46次感染事件,感染发生的中位时间为CAR-T 细胞输注后9天。28天内感染事件的累积发生率为56.9%(95%CI:50.4-61.3%),其中细菌和真菌感染是最常见的早期感染事件。多因素分析结果显示,淋巴细胞清除化疗前较低的中性粒细胞计数(OR = 3.875,P = 0.041)和更严重的细胞因子释放综合征并发症(OR = 4.141,P = 0.037)被确定为与早期感染事件可能性增加相关的独立危险因素。

本研究考察了早期感染事件的分布并确定了潜在的危险因素,旨在为临床医生提供指导,以实施更有效的干预策略,降低治疗相关死亡率并改善患者预后。

本研究已在中国临床试验注册中心注册(试验注册号:ChiCTR2000041054)。

展开英文摘要原文

The CLL1-targeted chimeric antigen receptor T (CAR-T) cell therapy offers a novel therapeutic approach for refractory or relapsed acute myeloid leukemia (AML). The targeted elimination of tumor cells by CLL1 CAR-T therapy also induces cytotoxic effects on neutrophils, leading to a severe granulocytopenia, thereby significantly increasing the risk of infectious complications during CAR-T therapy.

However, the infectious complications associated with this strategy have not been comprehensively investigated. The objective of this study was to evaluate the incidence rate of infectious complications within a 28-day period in a cohort of 51 patients who underwent CLL1 CAR-T cell infusion. Meanwhile, the univariate and multivariate analyses were employed to access the risk factors of infectious complications during CLL1 CAR-T therapy. The study observed a total of 46 infection events in 32 out of 51 patients (63%), with the median onset of infection occurring at 9 days following CAR-T cell infusion.

The cumulative incidence of infection events within 28 days was 56. 9% (95%CI: 50. 4-61. 3%), with bacterial and fungal infections being the most prevalent early infection events. The results of multivariate analysis revealed that a lower neutrophil counts prior to lymphodepletion chemotherapy (OR = 3. 875, P = 0. 041) and more severe complications of cytokine release syndrome (OR = 4. 141, P = 0. 037) were identified as independent risk factors associated with an increased likelihood of early infection events.

This study examined the distribution of early infection events and identified potential risk factors, with the goal of offering guidance to physicians on implementing more effective intervention strategies to decrease treatment-related mortality rates and improve patient prognosis.

This study has been registered in the Chinese Clinical Trial Registry (Trial registration number: ChiCTR2000041054).

论文信息

作者
Xu J、Zhang H、Zhao Y、Zhang X、Guo S、Shi X、Xiao X、Lyu H
第一作者单位
The First Central Clinical College of Tianjin Medical University, Tianjin, 300380, China.China
通讯作者单位
Department of Hematology, Tianjin First Central Hospital, No.2 Baoshanxi Rd, Xiqing District,, 300380, Tianjin, China. mingfengzhao@sina.com.China
期刊
Cancer immunology, immunotherapy : CII2025 Mar 15
原文标识
PubMed 40088283 · DOI 10.1007/s00262-025-03998-1