Abstract
PURPOSE: 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). METHODS: This open-label study evaluated UC-MSC infusion (administer 1 × 10(6)/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). RESULTS: 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 (P = .033 and P = .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 P < .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, P < .001). MSC infusion did not influence the cumulative incidence of relapse (P = .34) and nonrelapse mortality (P = .45). CONCLUSION: 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.