Relationship Of Graft Immune Cell Components On Graft-versus-host Disease And Immune Reconstruction In Unrelated Donor Peripheral Blood Stem Cell Transplantation

Purpose1.To explore the relationship between immune cell components and GVHD in unrelated donor grafts.2.To explore the relationship between the components of immune cells in grafts and the reconstruction of immune cells after transplantation.3.To explore the relationship between the occurrence of GVHD and immune cell reconstruction after transplantation.MethodThe clinical data of 73 patients with hematological diseases who underwent unrelated donor PBSCT in our hospital from July 2013 to June 2018 were analyzed retrospectively.The number of mononuclear cells(MNC),CD34+cells,CD3+T lymphocytes,CD4+cells,CD8+cells,NK cells,NKT cells and Treg cells in the grafts were detected by flow cytometry.The percentage of CD3+,CD4+,CD8+,Treg and NK cells in peripheral blood lymphocytes was detected at 1 month,3 months,6 months and 12 months after transplantation.According to the median,the values of cell components in the graft were divided into higher number group and lower number group.According to Seattle GVHD classification,patients with GVHD were divided into aGVHD group,?-? degree aGVHD group,III-IV degree aGVHD group,cGVHD group,localized cGVHD group and extensive cGVHD group.SPSS 24.0 software was used for statistical analysis,survival analysis was performed with Kaplan-Meier method and Log-rank test,Cox regression analysis was used for multivariate analysis,and the relationship between graft cell composition and immune reconstruction was analyzed by correlation analysis.Result1.Hematopoietic reconstitution was achieved in all patients,and the median implantation time of neutrophils and platelets was 12 days(9-20 days)and 13 days(9-43 days),respectively.The number of CD34+cells,CD4+cells and CD8+cells was negatively correlated with granulocyte reconstitution time(r=-0.23,-0.281 and-0.256,P=0.05,0.016 and 0.029,respectively),while there was no correlation between cell components and platelet reconstitution time.2.As of September 30,2019,27 patients(37%)died and 46 patients(63%)survived.The OS rate 3 years after transplantation was 63.4%±5.8%.6 patients(8.2%)relapsed,and the rate of DFS 3 years after transplantation was 89.6%±4.1%.Statistical analysis showed that the higher number of CD34+cells in the graft could increase the rate of OS after transplantation(75.7%±7.1%VS 43.9%±9.7%,P=0.041).The number of other graft cell components had no effect on the rate of OS and DFS after transplantation(P>0.05).3.Univariate analysis showed that patients with older age,blood group incompatibility,HLA mismatch,higher number of CD3+T cells and lower number of Treg cells had a higher incidence of ?-? degree aGVHD after transplantation(all P<0.05).The incidence of aGVHD after transplantation was lower in the group with higher number of CD34+cells in the graft(51.4%±8.2%VS 77.8%±6.9%,P=0.023).The incidence of ?-? degree aGVHD in adult female donor group was higher than that in adult female donor group(P<0.05).The incidence of ?-? degree aGVHD and cGVHD was lower in patients with higher number of Treg cells after transplantation.Multivariate analysis showed that older patients(OR=0.364,95%CI=0.13 3?0.996,P=0.049),donor-recipient HLA mismatch(OR=3.162,95%CI=1.220?8.196,P=0.018),higher number of CD3+T cells(OR=0.191,95%CI=0.067?0.541,P=0.002)and lower number of Treg cells(OR-3.151,95%CI=1.222?8.122,P=0.018)were independent risk factors for ?-?degree aG VHD after transplantation.4.In the first 100 days after transplantation,the occurrence of ?-? degree aGVHD was negatively correlated with the reconstruction of NK cells,CD4+cells and CD8+cells.Conclusion1.In unrelated donor PBSCT,the incidence of aGVHD after transplantation of high number of CD34+cells in grafts is low,and the rate of OS can be increased.2.The higher number of CD3+ cells,the lower number of Treg cells in the graft,the older patient,and the HLA mismatch between donors and recipients is an independent risk factor for the occurrence of ?-? degree aGVHD.3.A high number of Treg cells in the graft is beneficial to reduce the incidence of acute and chronic GVHD after transplantation.4.The reconstruction of CD4+cells,CD8+cells and NK cells after transplantation is related to the occurrence of ?-? degree aGVHD reconstruction.