Increased EBV infection and relapse following haploidentical hematopoietic cell transplantation in the era of letermovir for cytomegalovirus prophylaxis: a propensity score matching analysis

Background Letermovir (LTV) is an effective strategy for cytomegalovirus (CMV) reactivation prophylaxis and is increasingly used for allogeneic hematopoietic stem cell transplantation. However, it carries the risk of delayed immune reconstitution. This retrospective study assessed the impact of primary LTV prophylaxis on viral infections, disease relapse, and immune reconstitution in haploidentical hematopoietic stem cell transplantation (haplo-HSCT) recipients. Methods Among 462 patients from Nanfang Hospital, propensity score matching created two cohorts: 106 with LTV prophylaxis and 212 without LTV prophylaxis. EBV/CMV infection, relapse, and survival were analyzed by competing risk models and Cox regression. Immune reconstitution and function were assessed by flow cytometry. Results LTV prophylaxis had protective effects against CMV viremia, with a 1-year incidence of 32.1% in the LTV group compared with 46.2% in the non-LTV group (P = 0.009). However, the 1-year cumulative incidence of EBV viremia was significantly higher in the LTV group than in the non-LTV group (38.7% vs.13.7%, P<0.001). On multivariate analysis, LTV prophylaxis was a protective factor for CMV viremia (HR = 0.54, P = 0.014) but a risk factor for EBV viremia (HR = 2.69, P<0.001). Additionally, the 1-year cumulative incidence of relapse post-HSCT was notably higher in the LTV group than in the non-LTV group (13.2% vs. 6.1%, P = 0.032). In multivariate analysis, LTV prophylaxis was an independent risk factor for relapse (HR = 2.56, P = 0.024). Lymphocyte subset counts and functions post-transplantation were significantly lower in the LTV group than in the non-LTV group. Conclusion LTV prophylaxis might play a dual role in haplo-HSCT recipients, reducing CMV infection but increasing EBV infection and relapse.