Cytomegalovirus-specific T cell immunity reconstitution following allogeneic hematopoietic stem cell transplantation: a pilot stduy

Abstract

Purpose Reactivation of cytomegalovirus (CMV) leads to significant morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The reconstitution of CMV-specific T cells plays a crucial role in the antiviral response after allo-HSCT. However, the impact of CMV reactivation on the recovery of CMV-specific T cells in the early stages after allo-HSCT, particularly haploidentical HSCT, remains undisclosed. Methods We retrospectively examined CMV-specific T-cell recovery in 78 allo-HSCT recipients to assess the influence of clinically significant CMV infection (CS-CMVi) on CMV-specific T-cell restoration. Results Patients in CS-CMVi group displayed higher absolute quantities of CMV-specific IFN-γ+ T cells on day 30 (CD4+ T cells: 1.40 vs. 0.07 cells/µL, p = 0.02; CD8+ T cells: 1.64 vs. 0.15 cells/µL, p = 0.11), but lower counts on day 180 (CD4+ T cells: 1.06 vs. 5.95 cells/µL, p < 0.01; CD8+ T cells: 3.70 vs. 55.36 cells/µL, p = 0.04). Among patients receiving letermovir prophylaxis (LTV group), the recovery of CMV-specific CD8+ T cells was significantly delayed compared to those receiving preemptive therapy (PET group) from day 60. The LTV group was more likely to experience late-onset CMV reactivation if their absolute counts of polyfunctional CMV-specific CD4+ T cells or CD8+ T cells was below 2.01 (AUC = 0.78, p = 0.003) or 0.90 cells/µL (AUC = 0.89, p < 0.001). Conclusions In conclusion, our pilot study provides direct evidence that early episodes of CS-CMVi impair the recovery of CMV-specific T cells after allo-HSCT. Additionally, insufficient polyfunctional restoration would lead to late-onset CMV reactivation in LTV group.