Yao Han, Huang Ruihao, Fu Haixia, Lin Ren, Zhang Yanqi, Feng Yimei, Wang Yu, Chen Ting, Wang Xiaoqi, Zhu Lidan, Liu Jia, Liu Yuqing, Zhao Lu, Wang Lu, Kong Peiyan, Wen Qin, Zhang Cheng, Gao Li, Gao Lei, Liu Qifa, Zhang Xiaohui, Huang Xiaojun, Zhang Xi
Medical Center of Hematology, Institute of Science Innovation for Blood Ecology and Intelligent Cells, Xinqiao Hospital of Army Medical University, Chongqing, China.
Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing, China.
J Clin Oncol. 2025 Jun 10;43(17):1997-2006. doi: 10.1200/JCO-24-02119. Epub 2025 Apr 15.
The aim of this open-label, multicenter, randomized controlled trial was to determine the efficacy and safety of sequential umbilical cord-derived mesenchymal stem cell (UC-MSC) infusion for graft-versus-host disease (GVHD) prevention within 3 months of haploidentical hematopoietic stem cell transplantation (haplo-HSCT).
This open-label study evaluated UC-MSC infusion (administer 1 × 10/kg 4 hours before the commencement of day 0, once weekly for the first month after transplantation, once every 2 weeks for the second month, and once during the third month, totaling eight doses). The primary end point was the 2-year cumulative incidence of severe chronic GVHD (cGVHD).
In the primary analysis, 192 qualified participants between age 18 and 60 years with haplo-HSCT in three transplant centers in China were enrolled and randomly assigned to the MSC and control groups. In the primary analysis, the estimated 2-year cumulative incidence of severe cGVHD and all grades of cGVHD was lower in the MSC group than in the control group ( = .033 and = .022). The cumulative incidence of grade 1 to 4, 2 to 4, and 3 to 4 acute GVHD (aGVHD) in patients in the MSC group significantly decreased (all < .001). The 3-year GVHD-free and relapse-free survival (GRFS) rate in the MSC group was 62.4%, which was significantly higher than that in the control group (32.0%, hazard ratio [HR], 0.34, < .001). MSC infusion did not influence the cumulative incidence of relapse ( .34) and nonrelapse mortality ( .45).
Our findings suggest that sequential infusion of MSCs within 3 months after haplo-HSCT significantly reduced both the incidence and severity of cGVHD and aGVHD, manifesting as a better GRFS rate for patients.
本开放标签、多中心、随机对照试验的目的是确定单倍体造血干细胞移植（haplo-HSCT）后3个月内序贯输注脐带间充质干细胞（UC-MSC）预防移植物抗宿主病（GVHD）的疗效和安全性。
本开放标签研究评估了UC-MSC输注（在第0天开始前4小时给予1×10/kg，移植后第一个月每周一次，第二个月每2周一次，第三个月一次，共八剂）。主要终点是严重慢性GVHD（cGVHD）的2年累积发病率。
在初步分析中，中国三个移植中心192名年龄在18至60岁之间接受haplo-HSCT的合格参与者被纳入并随机分配到MSC组和对照组。在初步分析中，MSC组严重cGVHD和所有级别的cGVHD的估计2年累积发病率低于对照组（=0.033和=0.022）。MSC组患者1至4级、2至4级和3至4级急性GVHD（aGVHD）的累积发病率显著降低（均<0.001）。MSC组的3年无GVHD和无复发生存率（GRFS）为62.4%，显著高于对照组（32.0%，风险比[HR]，0.34，<0.001）。MSC输注不影响复发的累积发病率（=0.34）和非复发死亡率（=0.45）。
我们的研究结果表明，haplo-HSCT后3个月内序贯输注MSC可显著降低cGVHD和aGVHD的发病率和严重程度，表现为患者有更好的GRFS率。
