Early T-Lymphocyte Immune Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation And Its Correlation With Acute Graft-Versus-Host Disease

Objective:To investigate the recovery of T lymphocyte subsets in peripheral blood at the early stage of allogeneic hematopoietic stem cell transplantation(allo-HSCT)and the related factors affecting the recovery of T lymphocyte subsets.To analyze the correlation between early peripheral blood T lymphocyte subsets and acute graft versus host disease(a GVHD),and to explore its impact on survival and recurrence.Methods:The clinical data of 97 patients who underwent allo-HSCT from January 1,2019 to June 1,2022 in Shanxi Bethune Hospital were analyzed retrospectively.Peripheral blood samples were taken from patients at 7 time points before and after transplantation,14,21,30,60,90,120,and the absolute count of CD3~+T,CD4~+T,CD8~+T lymphocyte subsets at each time point was calculated.The effects of recipient age,HLA consistency,whether to use ATG for pretreatment,stem cell source,infection and other factors on the count of lymphoid subgroups were analyzed.Analyze the correlation between lymphocyte count and a GVHD,select the optimal critical value of CD4~+T cells before the onset of a GVHD,and evaluate the impact of CD4~+T cell count array on survival and recurrence.Results:1.The rate of immune reconstitution after transplantation is different.CD8~+T reconstruction was fast,reaching(655.86±278.44)/μl 90 days after transplantation,exceeded the normal level;On the contrary,the recovery of CD4~+T cells was slow,and the number of CD4~+T cells was reaching(385.67±157.72)/μl at the 120th day after transplantation.It is still far below the normal level.Long-term CD4~+T/CD8~+T ratio inversion after transplantation.2.Factors affecting immune reconstitution:(1)Age:The number of T lymphocyte subsets in the group aged<29 years after transplantation is higher than that in the group aged≥29 years,but it mainly affects the CD4~+T cell count.At 30 and 60 days after transplantation,the number of CD4~+T cells in the<29 year old group was significantly higher than that in the≥29 year old group(P values were 0.023 and 0.037,respectively).(2)HLA compatibility:The immune reconstitution in the HLA full compatibility group is faster than that in the HLA half compatibility group,mainly affecting CD4~+T cells.The CD4~+T lymphocyte in the HLA full compatibility group was(108.40±93.74/ul vs 48.09±63.27/ul),(179.31±85.33/ul vs 52.68±29.46/ul),(206.48±103.10/ul vs 127.69±79.18/ul),respectively,compared with haploid transplantation group on the 14th,21st,30th and 90th day after transplantation,P<0.05.(3)With or without ATG in the conditional regimen:The T lymphocyte subsets count in the ATG free group recovered faster than that in the ATG group at the early stage of transplantation.It mainly affects the reconstruction of CD4~+T cells.On the 14th,21st,and 30th days after transplantation,the ATG free group was significantly higher than the ATG group(P values were 0.009,0.005,and 0.017,respectively).(4)Source of stem cells:The T cell count in the peripheral blood stem cell transplantation group was significantly higher than that in the peripheral blood+bone marrow stem cell transplantation group,with a particularly significant difference in the CD4~+T cell count.On the 14th,21st,30th,60th,90th,and 120th days after transplantation,the CD4~+T cell count in the peripheral blood stem cell transplantation group was significantly higher(P values were 0.023,0.011,0.003,0.001,0.037,and0.048,respectively).(5)Infection:At 28 and 90 days after transplantation,it was found that the CD3~+T,CD4~+T,and CD8~+T cell counts in the infected group were lower than those in the non infected group,but the difference was not statistically significant(P>0.05).3.Correlative analysis of T lymphocyte subsets count with a GVHD and survival prognosis(1)The median onset time of a GVHD was the 27th day after transplantation.We found that before the onset of a GVHD,there was a significant positive correlation between the onset of a GVHD and CD4~+T and CD8~+T.After the onset of a GVHD and before the end of our observation point,there was a significant negative correlation between the onset of a GVHD and CD4~+T and CD8~+T,with a statistically significant difference.(2)Before the occurrence of a GVHD,the ROC curve was used to determine the optimal threshold for CD4~+T cell count,and it was found that the CD4~+T cell count array had a higher survival rate and a lower recurrence rate.Conclusion:1.The rate of T cell immune reconstitution after allogeneic hematopoietic stem cell transplantation is different.CD4~+T cell reconstitution is slow,and CD8~+T reconstitution is rapid,resulting in long-term ratio inversion after transplantation.Young patients,pre-treatment without ATG,HLA full compatibility transplantation,peripheral blood hematopoietic stem cell transplantation,and non-infection have a relatively small impact on immune reconstitution.2.Before the occurrence of a GVHD,a GVHD was related to the high count of CD4~+T and CD8~+T;The occurrence and treatment of a GVHD will reduce the CD4~+T and CD8~+T counts.High CD4~+T cell count at early stage will result in better OS and lower recurrence rate.