[The dual effects of letermovir in allogeneic hematopoietic stem cell transplantation]

Human cytomegalovirus (HCMV) infection is one of the most common and severe viral complications following allogeneic hematopoietic stem cell transplantation (allo-HSCT), significantly increasing the risk of graft-versus-host disease (GVHD) and non-relapse mortality. Letermovir, as the first inhibitor targeting the HCMV terminase complex, blocks the cleavage of viral DNA and its packaging into viral capsids, demonstrating remarkable efficacy in early post-transplant HCMV prophylaxis. It significantly reduces the incidence of clinically significant HCMV infection (csCMVi) and indirectly contributes to improved GVHD- and relapse-free survival. However, while the potent viral suppression of this treatment provides clinical benefits, it also limits viral antigen exposure, which leads to delays in the reconstitution of HCMV-specific T cells and NK cells and consquently the increased risk of late-onset HCMV reactivation after drug discontinuation. This may also be associated with an elevated risk of Epstein-Barr virus reactivation and post-transplant lymphoproliferative disease (PTLD). This review aims to systematically summarize the dual effects of letermovir in allo-HSCT and analyzes its pharmacological mechanisms, clinical efficacy, impact on immune reconstitution, and potential consequences. Furthermore, it explores individualized management strategies based on immune monitoring to provide a theoretical basis for optimizing clinical practice.