Efficacy Of Unrelated Donor Hematopoietic Stem Cell Transplant With Co-transfusion Of Multipotent Mesenchymal Cells In Paediatric Severe Aplastic Anemia

Objective The purpose of this study was to observe the efficacy of unrelated donor hematopoietic stem cell transplant(HSCT)with co-transfusion of multipotent mesenchymal cells(MSCs)in paediatric severe aplastic anemia(SAA).Methods we analyzed 25 children with SAA who had received unrelated donor hematopoietic stem cell with co-transfusion of mesenchymal cells from November2009 to August 2015.All patients received a conditioning regimen consisting of Flu,CTX and ATG.GVHD prophylaxis was conducted using a combination of drugs including CSA,MTXand MMF.In this study,we used umbilical cord-derived MSCs,the MSCs were intravenously infused at a mean dose of 1.25 x 106/kg(range: 0.85–2.5106/kg)over about 30 min,followed by infusion of the hematopoietic grafts.All the patients received granulocyte colony stimulating factor(G-CSF)mobilized peripheral blood stem cell(PBSC)from unrelated donor(UD).There were 13 human leukocyte antigen(HLA)matched donors and 12 donors who had disparities at one or two loci.The average total nucleated cell number was 15.63(6.09-30.4)x108 / kg,and the average CD34+ cells number was of 9.94(2.62-26.7)x106 / kg.The hematopoietic recovery and transplant-associated complications were monitored.SPSS 17.0 was used to analyze the difference of the incidence of a GVHD between the leukocyte antigen(HLA)matched patients and one or two loci mismatched patients.Results MSCs infusion was safe,and no acute or long-term adverse reactions were observed.ALL patients achieved rapid hematopoietic reconstruction after transplantation,and the average time of neutrophil and platelet recovery was 12.52 days and 15.12 days respectively,but delayed rejection occurred in one case four months after transplantation.11 cases developed gradeⅠacute graft-versus-host disease(a GVHD),2 cases developed grade Ⅲ a GVHD and one of them developed diffuse chronic graft-versus-host(c GVHD).The total incidence of a GVHD was 52%,the incidence of grade II-IV a GVHD was 8%.Cytomegalovirus viremia was observed in 20 patients.14 children occured infection.2 cases developed hemorrhagic cystitis,1case was diagnosed as posterior reversible encephalopathy syndrome,and 1 patient developed post-transplantation lymphoproliferative disorders(PTLD).With a median following-up time of 23 months,all the children are alive,one of them had develped PTLD and recieved Rituximab and chemotherapy,delayed rejection occurred in this patient four months after transplantation,then haplo-identical HSCT with his father as the donor was performed and successful engrafment was achieved.1 case is currently receiving rituxan treatment because of low platelets,but he is transfusion-independent.The incidence of a GVHD was lower in HLA 10/10 matched group(30.77% versus 75 %,P=0.047).Conclusion The unrelated donor HSCT with co-transfusion of MSCss in paediatric SAA is safe and effective.