肿瘤细胞治疗研究
英文原题：Pre-infusion risk factors predict severe infectious complications of CAR T-cell therapy in pediatric and adult patients with B-ALL.
高龄、既往感染史、基线血小板减少以及较高的 ALL-HT 评分是接受 CAR-T 细胞治疗的 B-ALL 患者发生严重感染的强力独立危险因素。
背景：嵌合抗原受体（CAR）T细胞可治愈B细胞急性淋巴细胞白血病（B-ALL），但其疗效可能受严重感染等危及生命的不良事件限制。B-ALL中的免疫效应细胞相关血液学毒性和继发性免疫缺陷可能尤其严重，因此必须了解输注前严重感染风险。ALL-HEMATOTOX（ALL-HT）评分是近期验证的一项预测B-ALL中CAR相关血液学毒性的工具，但ALL-HT与输注后严重感染的关系尚未得到全面评估。 方法：这项多中心回顾性分析评估在3家机构接受CD19和CD22靶向CAR-T细胞治疗的B-ALL患者，考察ALL-HT及其他输注前变量与第+60天前严重感染的关联。根据微生物学、组织病理学或临床综合征识别感染，并按CTCAE V.5.0分级；严重感染定义为3级。使用多变量Logistic回归和Cox比例风险模型确定独立感染风险因素。 结果：350例接受CAR-T细胞治疗的患者中，79例（23%）在CAR-T后第+60天内发生严重感染，包括8例4级（危及生命）感染和5例5级（致死）感染。血流感染最常见，占严重感染患者的67%。多变量分析显示，输注前与严重感染相关的因素包括年龄较大（OR 1.35，1.1–1.6；p=0.002）、既往严重感染（OR 2.1，1.2–3.7；p=0.009）及ALL-HT评分较高（OR 1.15，1.01–1.31；p=0.04）。根据ALL-HT评分为高危（HR）的患者，其感染风险高于低危患者（HR 1.4，1.1–2.7；p=0.014）。24例（7%）患者发生多次严重感染。亚组分析显示，ALL-HT感染风险主要由基线血小板减少驱动，血小板计数低于50,000/μL强烈预测感染风险（HR 2.2，1.3–3.6；p=0.002）。输注后感染风险与中性粒细胞减少持续时间较长相关（OR 1.26，1.1–1.4；p<0.001）。 结论：年龄较大、既往感染史、基线血小板减少和ALL-HT评分较高，是接受CAR-T治疗的B-ALL患者发生严重感染的强效独立风险因素。这些因素可用于制定个体化风险缓解措施，预防这一高危患者群体严重感染。 试验注册号：NCT03827343。
BACKGROUND: Despite the curative potential for chimeric antigen receptor (CAR) T-cells in B-cell acute lymphoblastic leukemia (B-ALL), efficacy can be limited by life-threatening adverse events such as severe infections. As immune effector cell-associated hematotoxicity and secondary immunodeficiency may be particularly profound in B-ALL, understanding pre-infusion risk of severe infection is imperative. The ALL-HEMATOTOX (ALL-HT) score is a recently validated tool designed to predict CAR-associated hematotoxicity in B-ALL, but the relationship between ALL-HT and severe infections post-infusion has not yet been comprehensively assessed. METHODS: In this multicenter, retrospective analysis, we evaluated ALL-HT and other pre-infusion variables for an association with severe infection through day+60 (D+60) in patients with B-ALL treated with CD19 and CD22-based CAR T-cell constructs across three institutions. Infections were identified by microbiology, histopathology, or as a clinical syndrome and graded by CTCAE (Common Terminology Criteria for Adverse Events) V.5.0. Severe infections were defined as grade 3. Multivariable logistic regression and Cox proportional hazard models were constructed to identify independent risk factors for infection. RESULTS: Across 350 patients receiving CAR T-cells, 79 (23%) developed a severe infection within day+60 post-CAR, including 8 patients with grade 4 (life-threatening) infection and 5 patients with grade 5 (fatal) infections. Bloodstream infections were the most common, comprising 67% of those with severe infections. In multivariable analysis, pre-infusion factors associated with severe infection included older age (OR 1.35 (1.1-1.6), p=0.002), prior severe infection (OR 2.1 (1.2-3.7), p=0.009), and a higher ALL-HT score (OR 1.15 (1.01-1.31), p=0.04). Patients classified as high-risk (HR) by ALL-HT had a greater risk of infection compared with low-risk patients (HR 1.4 (1.1-2.7), p=0.014).Multiple severe infections occurred in 24 patients (7%). In a subanalysis, ALL-HT risk of infection was primarily driven by baseline thrombocytopenia, with a cut-off of 50 000 platelets/ L strongly predicting risk of infection (HR 2.2 (1.3-3.6), p=0.002). Post-infusion infection risk was driven by a longer duration of neutropenia (OR 1.26 (1.1-1.4), p<0.001). CONCLUSIONS: Older age, prior infection history, baseline thrombocytopenia, and higher ALL-HT scores are strong independent risk factors for severe infection among patients with B-ALL receiving CAR T-cells. These factors may guide individualized risk mitigation to prevent severe infections in this high-risk patient population. TRIAL REGISTRATION NUMBER: NCT03827343.
MEMBER ACCOUNT
登录成功会直接打开下一页。
