Correlation Between T Lymphocyte Immune Reconstitution And Virus Infection After Hematopoietic Stem Cell Transplantation

Objective:To analyse the pattern of T-lymphocyte reconstitution in haematopoietic stem cell transplant patients within six months after surgery and its influencing factors,as well as to explore the correlation between T-lymphocyte reconstitution on viral infection and the impact on clinical prognosis.Methods:Retrospective analysis of the clinical data of 111 hematology patients who received hematopoietic stem cell transplantation at the Department of Hematology,Third Hospital of Shanxi Medical University from October 2016 to October 2022,including 24 cases of autologous haematopoietic stem cell transplantation(auto-HSCT),18 cases of multiple myeloma(MM),2 cases of non-Hodgkin’s lymphoma(NHL)and 4 cases of acute myeloid leukaemia(AML);allogeneic haematopoietic stem cell transplantation(allo-HSCT)was performed in 87 cases,including 31 cases of acute myeloid leukaemia(AML),17 cases of acute lymphoblastic leukaemia(ALL),35 cases of aplastic anaemia(AA)and 4 cases of myelodysplastic syndrome(MDS).The absolute counts and ratios(CD4~+T/CD8~+T)of peripheral blood T-cell subsets(CD3~+T,CD4~+T,CD8~+T)were measured by flow cytometry at+14d,+30d,+60d,+90d,+120d,+150d,and+180d after transplantation.Real time quantitative PCR method was used to detect the DNA copy number of viruses(CMV,EBV),once per week within 100 days after transplantation,once per month within 100 days and 180 days,and once every two months after 180days.If there are symptoms of the urinary system,the BKV virus load should be tested.If there are symptoms of lip herpes and chickenpox,the HSV and VZV DNA copy numbers should be tested.If positive,the virus should be tested once a week until negative.EBV,CMV,BKV and HSV test samples are venous blood,BKV test samples also include urine in case of urinary system symptoms,HSV test samples can include cerebrospinal fluid in case of suspected HSV meningitis or encephalitis,and VZV test samples are blister fluid.Select the absolute count of lymphocyte subpopulations from peripheral blood of 30 healthy donors as a control.Results:1.T-lymphocyte reconstitution after transplantationCD3~+T lymphocytes were significantly lower than normal at+14d after transplantation,recovered gradually at+90d,and approached the control level at+180d;CD4~+T lymphocytes were significantly lower than normal at+14d after transplantation,recovered slowly,and were still far below the control level at+180d;CD8~+T lymphocytes decreased less than CD3~+T and CD4~+T lymphocytes at+14d after transplantation,and the number of CD8~+T lymphocytes recovered significantly at+90d after transplantation and exceeded the level of the control group;the CD4~+T/CD8~+T ratio was inverted all the time after transplantation.The T cell subpopulation counts recovered faster in transplanted patients in the age>35 years old,HLA all-compatible transplantation,and auto-HSCT groups;the T lymphocyte subpopulation count in patients with acute graft-versus-host disease(a GVHD)was lower than that in patients without acute graft-versus-host disease(a GVHD)the T cell subpopulation counts were lower in the group with hemorrhagic cystitis(HC)than in the group without hemorrhagic cystitis(HC);and T cell subpopulation reconstitution was delayed in the group with viral infections(CMV,EBV,BKV positive).2.T-lymphocyte reconstitution and viral infection after transplantationUnivariate analysis showed that T-cell reconstitution was negatively and weakly correlated with CMV,EBV,and BKV at different time points after transplantation;multifactorial analysis showed a negative correlation between+120d CD4~+T-cells and CMV infection after transplantation,and+120d CD4~+T cells<193.5/μL were strongly associated with CMV infection.3.T-lymphocyte reconstitution and clinical prognosis after transplantationUnivariate analysis showed that CMV disease significantly affected survival after transplantation;multifactorial COX regression analysis showed that patients with absolute CD3~+T-cell counts>850.5/u L and absolute CD4~+T-cell counts>142.5/u L after transplantation+180d had better survival.Conclusion:The recovery of lymphocyte subpopulation counts in patients after haematopoietic stem cell transplantation has its own pattern,with delayed recovery of lymphocyte subpopulations in patients with allogeneic haematopoietic stem cell transplantation,HLA haploidentical haematopoietic stem cell transplantation,the occurrence of a GVHD,the emergence of HC,and similarly,CMV,EBV and BKV infections may delay early lymphocyte recovery.Post-transplantation CD3~+T and CD4~+T cell reconstitution levels,especially CD4~+T cell reconstitution levels,are strongly correlated with viral infection.Peripheral blood lymphocyte counts at+120d post-transplantation help identify people at high risk of developing CMV infection early.Patients with absolute CD3~+T-cell counts>850.5/u L and absolute CD4~+T-cell counts>142.5/u L at+180d post-transplantation achieved better survival.