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与化疗相比,嵌合抗原受体T细胞疗法后进行异基因造血干细胞移植,血小板植入失败和慢性移植物抗宿主病的风险更高:一项倾向评分匹配分析。

Higher risk of platelet engraftment failure and chronic graft-versus-host disease after allogeneic haematopoietic stem cell transplantation following chimeric antigen receptor T-cell therapy compared to chemotherapy: A propensity score-matched analysis.

作者信息

Yang Luxin, Lai Xiaoyu, Liu Lizhen, Shi Jimin, Zhao Yanmin, Yu Jian, Wu Yibo, Fu Huarui, Hu Yongxian, Zhang Mingming, Huang He, Luo Yi

机构信息

Bone Marrow Transplantation Center of the First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China.

Institute of Hematology, Zhejiang University, Hangzhou, China.

出版信息

Br J Haematol. 2025 Jul;207(1):162-170. doi: 10.1111/bjh.20180. Epub 2025 Jun 4.

DOI:10.1111/bjh.20180
PMID:40464130
Abstract

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) has been reported to further sustain long-term leukaemia-free survival following chimeric antigen receptor T-cell (CAR-T) therapy. It remains unclear whether bridging CAR-T to allo-HSCT results in higher treatment-related toxicity and mortality. We conducted a retrospective study to compare outcomes between allo-HSCT after CAR-T or conventional chemotherapy. After propensity score matching, 62 patients with prior CAR-T therapy and 124 patients with chemotherapy were ultimately included. Patients in the CAR-T cohort had a longer duration time from diagnosis to transplant (p < 0.001) and more advanced disease status before HSCT (p < 0.001) than that of the chemotherapy cohort. Patients with prior CAR-T cell therapy had a lower 28-day platelet engraftment rates [Hazard Rate (HR) = 1.38, 95% Confidence Interval (CI), 1.02-1.87, p = 0.037]. Multivariate analysis revealed that CAR-T therapy increased the risk of moderate to severe chronic graft-versus-host disease (cGVHD) (HR = 2.5, 95% CI, 1.01-6.19, p = 0.048). Compared with patients in the chemotherapy cohort, those in the CAR-T cell cohort experienced a higher incidence of transplantation-associated thrombotic microangiopathy (6.5% vs. 0.8%, p = 0.03) and probable/possible invasive fungal disease (10.0% vs. 3.3%, p = 0.08). The relapse rate, non-relapse mortality, and survival were comparable between cohorts. Caution should be exercised in allo-HSCT following CAR-T therapy because of the higher risk of platelet engraftment failure and cGVHD compared to chemotherapy.

摘要

据报道,异基因造血干细胞移植(allo-HSCT)可在嵌合抗原受体T细胞(CAR-T)治疗后进一步维持长期无白血病生存。目前尚不清楚将CAR-T与allo-HSCT衔接是否会导致更高的治疗相关毒性和死亡率。我们进行了一项回顾性研究,以比较CAR-T治疗后或传统化疗后进行allo-HSCT的结果。经过倾向评分匹配,最终纳入了62例接受过CAR-T治疗的患者和124例接受化疗的患者。与化疗队列相比,CAR-T队列中的患者从诊断到移植的持续时间更长(p<0.001),HSCT前疾病状态更晚期(p<0.001)。既往接受CAR-T细胞治疗的患者28天血小板植入率较低[风险比(HR)=1.38,95%置信区间(CI),1.02-1.87,p=0.037]。多变量分析显示,CAR-T治疗增加了中重度慢性移植物抗宿主病(cGVHD)的风险(HR=2.5,95%CI,1.01-6.19,p=0.048)。与化疗队列中的患者相比,CAR-T细胞队列中的患者发生移植相关血栓性微血管病的发生率更高(6.5%对0.8%,p=0.03),以及可能/疑似侵袭性真菌病的发生率更高(10.0%对3.3%,p=0.08)。各队列之间的复发率、非复发死亡率和生存率相当。与化疗相比,CAR-T治疗后进行allo-HSCT时应谨慎,因为血小板植入失败和cGVHD的风险更高。

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