Letermovir prophylaxis for cytomegalovirus and immune reconstitution after allogeneic hematopoietic stem cell transplantation: A single-center real-world study

Abstract

Abstract Introduction: Letermovir prophylaxis is essential for preventing cytomegalovirus (CMV) reactivation in adult hematopoietic stem cell transplant (HSCT) recipients. However, real-world data are still lacking. The aim of this study was to evaluate the efficacy of letermovir for CMV prophylaxis after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its influence on immune reconstitution. Methods: A retrospective review was conducted for 687 patients who underwent allo-HSCT at the Institute of Hematology and Blood Disease Hospital from January 2022 to November 2023. The relationship between letermovir administration and the occurrence of clinically significant cytomegalovirus infection (csCMVi) was observed, and immune reconstitution between days 91 and 180 after allo-HSCT was explored. Results: Among the 687 patients, 284 patients were administered letermovir for the prevention of CMV infection. Compared with the 403 patients who did not use letermovir, the incidence of csCMVi in the patients who used letermovir was significantly lower (25.4% vs. 58.6%, P=0.000), while the infection of EB virus (17.7% vs. 7.2%, P=0.000) and the incidence of EB virus-related post-transplant lymphoproliferative disorders (EBV-PTLD) (6.3% vs. 2.2%, P=0.006) were significantly higher. The peripheral blood lymphocyte reconstitution after 91-180 days of transplantation was significantly inhibited (median lymphocyte percentage in nucleated cells, 20.83% vs. 28.95%, P=0.000), and IgG and IgM were significantly decreased (median IgG, 7.77 g/L vs. 9.46 g/L, P=0.000; median IgM, 0.48 g/L vs. 0.61 g/L, P=0.009). In the letermovir group, the peripheral blood B lymphocyte reconstitution of patients with csCMVi was significantly lower than that of patients without infection (median B cell percentage in lymphocytes, 0.55% vs. 1.94%, P=0.017), and they were more likely to have EB virus infection (31.9% vs. 12.8%, P=0.000). Conclusion: Letermovir reduces the incidence of csCMVi after allo-HSCT, but it increases the risk of EBV/PTLD, which may be related to the influence of lymphocyte reconstitution.