Co-transplantation Of Mesenchymal Stem Cells During Allogeneic Hematopoietic Stem Cell Transplantation For Severe Aplastic Anemia:A Multi-center Retrospective Study Of 92 Patients

Objective:Mesenchymal stem cells(MSC)have the potential to improve overall outcomes of severe aplastic anemia(SAA)patients who are treated with allogeneic hematopoietic stem cell transplantation(allo-HSCT).Here,the study was designed to explore the safety and efficacy of MSC co-transplantation with allo-HSCT in SAA patients.Methods:A multi-center,retrospective study was conducted at 3 separate hospitals between January 2012 and December 2018.Eligible patients were allocated into the study group and control group.Patients in the study group received allo-HSCT with MSC infusion,while patients in the control group only received allo-HSCT.The MSC infusion dose was 0.5-3.0×10~6/kg,given at day+1 following hematopoietic stem cells(HSC)infusion.Adverse events were collected for safety evaluation in the study group.The primary endpoint of the study was overall survival(OS).Outcome measurements were extracted and analyzed statistically by using SPSS version 21.0 and Graphpad Prism 6.Results:Records from a total of 92 consecutive SAA patients who underwent allo-HSCT were analyzed.Forty-seven patients were transplanted with donor HSC only(control group),while 45 patients received MSC with HSC(study group).No adverse events happened in the study group.All patients achieved successful myeloid engraftment.There was no difference in time to engraftment or Gv HD rates between the two groups.A trend towards lower incidence of fatal infection was observed in the MSC group(4.4%vs.17%,P=0.091).Moreover,a significantly lower incidence of CMV replication was observed in the MSC group(26.7%vs 64.4%,P=0.008).With a median follow-up time of 911-days(29-2847),the OS was similar in both groups(79.7%vs.74.2%;P=0.41).A combination of bone marrow and peripheral blood as the source of HSC co-transplanted with MSC(n=20)resulted in improved survival(OS=95%)compared to HSC exclusively from peripheral blood.Conclusion:Collectively,our study of SAA patients suggests that co-transplantation of MSC and HSC can reduce infection and ameliorate post allo-HSCT prognosis for SAA,and when possible,donor bone marrow should be used as at least a partial source of HSC.