{"title":"CLL1 CAR-T细胞治疗急性髓性白血病后的感染并发症分布。","authors":"Jianmei Xu, Huan Zhang, Yifan Zhao, Xiaomei Zhang, Shujing Guo, Xiaoxue Shi, Xia Xiao, Hairong Lyu, Yu Zhang, Xiaoyuan He, Mingfeng Zhao","doi":"10.1007/s00262-025-03998-1","DOIUrl":null,"url":null,"abstract":"<p><p>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).</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 5","pages":"149"},"PeriodicalIF":4.6000,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910464/pdf/","citationCount":"0","resultStr":"{\"title\":\"Infectious complications distribution following CLL1 CAR-T cell therapy for acute myeloid leukemiass.\",\"authors\":\"Jianmei Xu, Huan Zhang, Yifan Zhao, Xiaomei Zhang, Shujing Guo, Xiaoxue Shi, Xia Xiao, Hairong Lyu, Yu Zhang, Xiaoyuan He, Mingfeng Zhao\",\"doi\":\"10.1007/s00262-025-03998-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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).</p>\",\"PeriodicalId\":9595,\"journal\":{\"name\":\"Cancer Immunology, Immunotherapy\",\"volume\":\"74 5\",\"pages\":\"149\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2025-03-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910464/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Immunology, Immunotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00262-025-03998-1\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Immunology, Immunotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00262-025-03998-1","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
cll1靶向嵌合抗原受体T (CAR-T)细胞疗法为难治性或复发性急性髓性白血病(AML)提供了一种新的治疗方法。CLL1 CAR-T疗法对肿瘤细胞的靶向清除也会诱导中性粒细胞的细胞毒性作用,导致严重的粒细胞减少,从而显著增加CAR-T治疗期间感染性并发症的风险。然而,与该策略相关的感染并发症尚未得到全面调查。本研究的目的是评估51例接受CLL1 CAR-T细胞输注的患者在28天内感染性并发症的发生率。同时,采用单因素和多因素分析,探讨CLL1 CAR-T治疗过程中感染性并发症的危险因素。该研究观察到51例患者中32例(63%)共46例感染事件,中位感染发生在CAR-T细胞输注后9天。28 d内感染事件的累计发生率为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,淋巴细胞耗损化疗前较低的中性粒细胞计数(OR = 3.875, P = 0.041)和较严重的细胞因子释放综合征并发症(OR = 4.141, P = 0.037)是早期感染事件可能性增加的独立危险因素。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,旨在指导医生实施更有效的干预策略,以降低治疗相关死亡率,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)。
Infectious complications distribution following CLL1 CAR-T cell therapy for acute myeloid leukemiass.
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).
期刊介绍:
Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions.
The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.