Co-Transplantation of Mesenchymal Stem Cells Can Ameliorates Acute Gvhd and Viremia after Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia: A Multi-Center Retrospective Study of 119 Patients

BACKGROUD:Mesenchymal stem cells (MSCs) are known to exhibit immunomodulatory, anti-inflammatory, and pro-angiogenic properties, and therefore have the potential to improve the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe aplastic anemia (AA).

OBJECTIVE: To explore the efficacy and safety of allo-HSCT by co-transplantation with MSCs in AA patients.

METHODS: We conducted a multi-center retrospective study to comparing the incidence and severity of acute GvHD, transplant-related complication and overall survival (OS) of allo-HSCT with or without co-injection of MSCs in AA patients. A total of 119 consecutive severe AA patients (64 males/55 females) undergoing allo-HSCT at 4 hospitals from January 2012 to February 2018 were analyzed. The median age of the patients is 23 (range 1-56 years). Patients received conditioning regimens based on cyclophosphamide or busulfan, among whom 50 (42%) were MSD-HSCT, 21(17.6%) MUD-HSCT and 48 (40.4%) haplo-HSCT. All patients received cyclosporine A with short course methotrexate for prevention of GVHD. 89 patients transplanted with donor HSCs only, and 30 patients transplanted with HSCs and MSCs .MSCs infusion dose was 0.5-3.0×10⁶/kg, at -1~+1 days following HSCs infusion. None of these patients had severe infection or organ failure before HSCT.

RESULTS: The two groups were well matched demographically. All patients achieved successful engraftment within one month post transplant. There was no difference in time to leukocyte and platelet engraftment in the two groups. The incidence of aGVHD grade II-IV (7.9 % versus 6.7 %, P =1.000) was similar in the HSC versus MSC groups, but there was a trend to a lower incidence of aGVHD grade III-IV in the MSC group (3.4% versus 0%, P=1.0). Moreover, a lower incidence of viremia in the MSC group was observed (CMV: 26.7% vs 62.9%, P < 0.001; EBV: 50% vs 80.9%, P = 0.002).With a median follow-up time of 811 days (range:28-2348days),the 2-yr OS was similar in both groups (82.8% versus 71.1%, P =0.498). A combination of bone marrow and peripheral blood as the sources of stem cells co-transplanted with MSCs (n=9) demonstrated an improved survival benefit (2-yr OS=100%).

CONCLUSION: Co-transplantation with MSCs could ameliorate the challenges of aGVHD and viremia and facilitate survival in allo-HSCT for AA patients.