Clinical and Immunological Characteristics of Patients with CMV Infection after Allogeneic Hematopoietic Stem Cell Transplantation

Objective To investigate the significance of peripheral blood lymphocyte subsets in distinguishing the cytomegalovirus (CMV) reactivation after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods We included 50 allo-HSCT patients with CMV infection and 47 without, treated at Beijing Ludaopei Hospital from May 2021 to January 2023. Clinical data and lymphocyte subsets at +1 month post-transplantation was collected. The absolute number of lymphocytes and their subsets were analyzed for their predictive significance in patients with CMV infection. Results1. 22% (11/50) of CMV-infected patients had CMV disease with a median viral load of 1600 (1400-5800) copies/ml, significantly higher than 970 (670-2300) copies/ml in patients without CMV disease (z=-2.281, P=0.029).Regardless of whether CMV disease was present, the majority of patients experienced CMV infection in the early post-transplant period.2 The overall survival (OS) at 1 year and at the end of follow-up for patients in the CMV infection group was 80% (40/50), and 87.2% (41/47) for patients in the non-CMV infection group, with no statistically significant difference(c2 = 0.231, P = 0.630). . 3 Infection rate was 30% (6/20) in the ATLG group, significantly lower than 57.1% (44/77) in the ATG group (z=4.683, P=0.030). The number of CD34+ cells transfused in the CMV group was significantly lower than in the non-infection group (Z=-2.944, P=0.003).There were no significant differences between the two groups in terms of patient gender, type of underlying disease, pre-transplant disease status (NR/CR), gender match between donor and recipient, blood type match, transplant type (matched related, unrelated, haploidentical), use of TBI, use of third-party donors, and occurrence of GVHD after transplantation (P > 0.05). 4 Compared to the non-infection group, the CMV infection group had poorer immune reconstitution, characterized by a lower percentage of CD3+ T and CD4+ T lymphocytes out of the total lymphocytes. The CMV infection group exhibited an immune state of viral activation, indicated by a higher percentage and absolute count of natural killer (NK) cells out of the lymphocytes, and higher percentages of CD3+CD38+ T cells out of CD3+ T cells, CD4+CD38+ T cells out of CD4+ T cells, and CD8+CD38+ T cells out of CD8+ T cells. Additionally, the CMV infection group had a higher percentage of CD8+ effector memory T cells (TEM) out of CD8+ lymphocytes, a lower percentage of CD4+ naive T cells out of CD4+ lymphocytes, a lower percentage of CD8+ terminal effector (EMRA) T cells out of CD8+ lymphocytes, and a lower percentage of CD8+ naive T cells out of CD8+ lymphocytes. Compared to the non-CMV infection group, T cells in the CMV infection group tended to be in an activated and exhausted state. 5 In the binary logistic regression model, the number of CD34 cells transfused to the patient, the percentage of CD3+CD38+ T cells out of CD3+ T cells, and the percentage of CD4+CD38+ T cells out of CD4+ lymphocytes after transplantation were important independent risk factors for infection. The receiver operating characteristic (ROC) curve results showed that the area under the curve (AUC) for the independent risk factors of CMV infection was 0.914 (>0.7, P < 0.001), with a decision value of 0.702, sensitivity = 0.857, and specificity = 0.844. Conclusion After allo-HSCT, the CMV group showed poorer immune reconstitution, an activated infection state, and T cell exhaustion. CD38 expression on T cells is a valuable marker for CMV infection.