Research Of The Correlation Between Donor TCR Diversity And Immune Reconstitution Of Recipients After Allogeneic Hematopoietic Stem Cell Transplantation

Objective:By detecting the TCR repertoire diversity of the donors of the recipients after allogeneic hematopoietic stem cell transplantation,we quantified the TCR repertoire of the specific donors and evaluated the immune status of the transplanted donors while further understanding the influence of the immune status of the donors on the immune reconstitution of the recipients after allo-HSCT.The correlation between donor TCR repertoire diversity and the clinical outcomes including relapse,infections,GVHD,OS,and PFS that related to immune reconstitution in recipients after allo-HSCT were analyzed at the same time.Methods:Peripheral blood samples from the recipients(n=102)of hematological malignancies who received allogeneic hematopoietic stem cells in the Department of Hematology of Sichuan Provincial People’s Hospital from July 2015 to October 2021 and transplanted after +100 day and the corresponding healthy donors’ samples were included.Clinical data of the recipients included gender,age at allo-HSCT,disease risk stratification,HLA type,minimal residual disease(MRD),CD34+ cell infusion volume and TNC infusion volume.The TCR diversity richness of donor TCRβ V-J gene combination and donor individual clone(oligoclone)were determined by the next generation deep TCRβ CDR3 high-throughput sequencing.According to the clinical prognostic indicators related to immune reconstitution of recipients after transplantation which included relapse,acute graft-versus-host disease(a GVHD),chronic graft-versus-host disease(c GVHD),infections(bacteria infection,fungal infection,cytomegalovirus(CMV)infection),overall survival(OS)and progression-free-survival(PFS),the correlation between donor TCR diversity and clinical outcomes that related to immune reconstitution of recipients was statistically analyzed by SPSS 23.0.Results:The donor TCRβ V-J gene combination(TCR diversity richness):1.a GVHD:(1)In the difference analysis: there was a statistically significant difference between the high and low groups in recipient with acute GVHD in terms of TCR richness in donors;(2)In the univariate and multivariate analyses:The donor TCR diversity richness was negatively associated with the incidence of a GVHD in recipients.2.c GVHD:(1)In the difference analysis:there was a statistically significant difference between the high and low groups in recipient chronic GVHD in terms of TCR richness in donors;(2)In the univariate and multivariate analyses:The donor TCR diversity richness was negatively associated with the incidence of c GVHD in recipients.3.In the survival analysis:compared to donors with D50>0.119,donors with D50<0.119 had a lower OS rate(P < 0.05).The individual clone from donors(oligoclone):1.Relapse:(1)In the difference analysis:there was a statistical difference between the two groups of with or without donor-derived oligoclonal for relapse of recipients after allo-HSCT;(2)In the univariate and multivariate analyses:the presence of the donor oligoclone was positively associated with the incidence of relapse in recipients.2.CMV infection:(1)In the difference analysis:there was a statistical difference between the two groups of with or without donor-derived oligoclonal for CMV infection of recipients after allo-HSCT;(2)In the univariate and multivariate analyses:the presence of the donor oligoclone was positively associated with the incidence of CMV infection in recipients.3.In the survival analysis:compared to without donor-derived oligoclonal,with donor-derived oligoclonal had a lower OS rate(P<0.02)and PFS rate(P<0.05).Multi-group comprehensive analysis of donor TCR diversity:1.Relapse:(1)In the difference analysis: there was a statistical difference between the two groups of low D50+with oligoclone and high D50+without oligoclone for relapse of recipients after allo-HSCT;Also there was a statistical difference between the two groups of high D50+without oligoclone and high D50+with oligoclone for relapse of recipients after allo-HSCT;(2)In the univariate analyses:the group of high D50+without oligoclone was negatively associated with the incidence of relapse in recipients.2.Infections:(1)In the difference analysis: there was a statistical difference between the two groups of low D50+without oligoclone and low D50+with oligoclone for infection of recipients after allo-HSCT;(2)In the univariate analyses:the group of low D50+with oligoclone was positively associated with the incidence of infection in recipients.3.a GVHD:(1)In the difference analysis: there was a statistical difference between the two groups of low D50+with oligoclone and high D50+with oligoclone for a GVHD of recipients after allo-HSCT;(2)In the univariate analyses:the group of high D50+with oligoclone was negatively associated with the incidence of a GVHD in recipients.Conclusion:(1)The donor TCRβ V-J gene combination(TCR diversity richness)shows the influence value on the incidence of a GVHD and c GVHD in recipients after allo-HSCT;(2)The presence of the individual clone from donors(oligoclone)has an impact on the relapse rate,the incidence of CMV infection,and PFS in recipients after allo-HSCT;(3)Both donor D50 and oligoclone shows the influence value on the OS in recipients;(4)The immune status of the donor has shown an impact on the immune reconstitution of the recipients after allo-HSCT,and the selection of the transplant donor can be optimized by evaluating the immune status of the donor in the future.