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Research Article: Clinical and immunological analysis of letermovir for preventing cytomegalovirus infection in children after hematopoietic stem cell transplantation

Date Published: 2026-04-22

Abstract:
The present study aimed to analyze the efficacy and safety of letermovir for preventing cytomegalovirus (CMV) infection and its impact on immune reconstitution in children after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The retrospective analysis included 83 patients who underwent allo-HSCT at Shanghai Children’s Hospital between January 2022 and June 2025 and survived ?100 days post-transplantation. Forty patients received letermovir as primary CMV prophylaxis (letermovir group), and 43 patients did not receive prophylaxis (control group). The primary outcomes were the post-transplantation incidence of CMV infection and CMV disease. Secondary outcomes included the effects of letermovir on acute graft-versus-host disease (aGVHD), hematopoietic reconstitution (time to neutrophil and platelet engraftment), liver function, incidences of Epstein-Barr virus (EBV) and BK virus (BKV) infections, and cellular immune reconstitution. The cumulative incidence of CMV infection post-transplantation was significantly lower in the letermovir group than in the control group (100 days: 7.5% vs. 53.5%, p<0.001; 180 days: 12.5% vs. 53.5%, p<0.001). No CMV disease occurred in either group. CMV reactivation occurred in 3 patients (7.5%) after discontinuation of letermovir. In the letermovir group, CMV infection occurred later [mean (range): 90.7 (31–168) days vs. 42.7 (16–90) days, p=0.050], lasted for a shorter duration [11.8 (7–15) days vs. 17.5 (4–39) days, p=0.042], and had a lower mean viral load [3,175 copies/ml vs. 30,407 copies/ml, p=0.393]. No significant differences were observed between the two groups in the time to neutrophil and platelet engraftment, incidence of grade II–IV and III–IV aGVHD, incidence of liver function abnormalities, or rates of EBV/BKV infection. Multivariate analysis showed that letermovir prophylaxis was an independent protective factor against CMV infection within 100 days post-transplantation (hazard ratio: 0.127, p=0.001). At 90 days, 180 days, and 1 year post-transplantation, the T lymphocyte and B lymphocyte counts were significantly lower in the letermovir group than in the control group (p<0.05). By 1 year post-transplantation, there was no difference in NK cell counts between the two groups (p=0.094). Within the letermovir group, only CD8 + T cell counts were significantly increased 1 year post-transplantation compared to pre-transplantation (p=0.027). Letermovir is safe and effective at reducing the risk of CMV infection in children after allo-HSCT, significantly delaying the onset of infection and shortening its duration. Although letermovir may impact early lymphocyte subset reconstitution, immune function can recover to pre-transplantation levels by 1 year post-transplantation.

Introduction:
Cytomegalovirus (CMV) infection is one of the most common complications following allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in pediatric patients. Due to children’s immature immune systems, the infection rate in CMV-seropositive recipients can reach 40-60%, significantly increasing transplant-related mortality ( 1 , 2 ). Although current prophylactic agents, such as ganciclovir, valganciclovir, and foscarnet, are somewhat effective, their use is limited by the risks of…

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