Abstract
Letermovir is an antiviral agent that significantly decreases the frequency of cytomegalovirus (CMV) infections following allogeneic hematopoietic stem cell transplantation (allo-HCT); however, its impact on Epstein-Barr virus (EBV) infection remains unclear. This multicenter, retrospective study involved 565 patients aged ≥ 18 years, who underwent allo-HCT between January 2021 and December 2023, with 284 receiving letermovir prophylaxis (letermovir group) and 281 not (control group). Cumulative incidences of clinically significant CMV infection (cs-CMVi), EBV DNAemia, EBV-disease and post-transplant lymphoproliferative disorder (PTLD) were compared between the groups. The 1-year cumulative incidence of EBV DNAemia did not differ significantly between the letermovir and control groups (58.1% vs. 52.7%, P = 0.3). However, letermovir prophylaxis was associated with a significantly higher incidence of PTLD within the first year post-HCT (7.39% vs. 1.80%, P = 0.00059). Multivariate analysis identified letermovir prophylaxis as an independent risk factor for PTLD (HR [95% CI]: 4.619 [1.458-10.278], P = 0.007). Letermovir altered the early reconstitution trajectory after allo-HCT, particularly in CD8(+) T cells. Our findings emphasized that although letermovir prophylaxis did not increase the risk of EBV DNAemia in allo-HCT recipients, it was associated with a higher incidence of PTLD. Further studies focusing on immune reconstitutiom dynamics are warranted to elucidate the underlying pathophysiology of EBV-PTLD under letermovir pressure.