Abstract
BackgroundRefractory acute graft versus host disease (aGVHD) is a major cause of death after allogenetic haematopoietic stem cell transplantation (allo-HSCT). This study evaluated the efficacy and safety of mesenchymal stem cells (MSCs) from bone marrow of a third-party donor to refractory aGVHD. MethodsTwenty-five patients with refractory aGVHD were enrolled in this prospective study. MSCs were given at a median dose of 1×106 cells/kg once weekly until aGVHD got complete response (CR) or MSCs were infused for a total of 8 doses. In order to evaluate infections, tumor relapse and cGVHD, 25 refractory aGVHD patients with MSCs treatment was matched with grade II-IV aGVHD patient without MSCs in the corresponding period ResultsAfter a total of 112 doses of MSCs were administered, with a median of 4 (range:2-12) doses per patient, the overall response (OR) rate for aGVHD was 72%,including CR in 56% and partial response (PR) in 16%. The efficacy of MSCs to aGVHD was significantly related with the severity and the number of involved organs of aGVHD, but unrelated with the onset timing of MSC. The incidence of CMV and EBV infections, including viremia and associated disease, was not different between MSCs and non-MSCs groups during aGVHD treatment and follow-up. At a median follow-up time of 126 (range: 49–1067) days post-transplantation, only two patients relapsed in MSCs group, compared with four relapsed in the control group. Tumor relapse was not different between the two groups (P=0.771). No toxic side effects and other secondary tumors were observed after MSCs treatment except for one EBV-associated post-transplant lymphoproliferative disorders (PTLD). The incidence of cGVHD in MSCs group, especially extensive cGVHD, was lower than that in non-MSCs group (25.0% Vs 68%, P=0.001; 20.0% Vs 64%, P=0.043, respectively). The ratio of CD3+CD4+/CD3+CD8+ T cells and the proportion of CD4+CD25+ regulatory T cells (Tregs) at 8 weeks after MSCs were higher than that before treatment (P=0.037 and P=0.020, respectively), and there were not different from the healthy people at 36 weeks after treatment. ConclusionsMSCs derived from bone marrow of third-party donors are effective to refractory aGVHD. It might not increase the risks of infections, tumor relapse, but reduce the incidence and severity of cGVHD. Disclosures:Liu:Science and Technology Program of Guangzhou of China (11A72121174): Research Funding; National Natural Science Foundation of China (Grant No.81000231, No.81270647): Research Funding; National Public Health Grand Research Foundation (Grant No. 201202017): Research Funding; 863 Program (No. 2011AA020105): Research Funding.
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