ArticleFrontiers in immunology2026
Letermovir does not affect long-term polyclonal immune reconstitution after allogeneic hematopoietic stem cell transplantation with ATG-based GvHD prophylaxis.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Letermovir (LET) is an effective prophylaxis for human cytomegalovirus (HCMV) reactivations in HCMV-seropositive patients after allogeneic stem cell transplantation (allo-SCT). HCMV promotes polyfunctional T-cell responses, leading to HCMV-specific immune reconstitution (IR), thus contributing to polyclonal IR. Methods: We retrospectively analyzed HCMV-seropositive patients undergoing allo-SCT with ATG-based GvHD prophylaxis to assess the impact of LET on timing and quality of polyclonal IR. Two cohorts were identified: a pre-emptive treatment (PET) historical cohort transplanted without LET prophylaxis and a LET cohort receiving LET until at least day +100. All patients underwent weekly HCMV-DNA monitoring during the first 100 days post-allo-SCT. Immune monitoring was performed by flow cytometry, quantifying CD3+CD4+, CD3+CD8+ T-cells, CD19+ B-cells, and CD56+CD16+ NK-cells monthly during the first year after transplantation. Results: A total of 276 HCMV-seropositive patients were analyzed, 99 (36%) in the LET cohort and 177 (64%) in the PET cohort. LET significantly reduced the incidence of clinically significant HCMV infections during the first 100 days [28.3% in the LET cohort vs. 68.4% in the PET cohort (p<0.001)]. The cumulative incidence of IR 18 months after allo-SCT was comparable in the two groups [24% in the LET cohort vs. 27% in the PET cohort (p=0.393)]. These data were supported by multivariable analysis (HR 1.2, 95% CI 0.74-1.95, p = 0.463). Distinct immune dynamics were observed in the LET cohort, including lower early CD8+ T-cell counts and earlier NK-cell expansion peak. Discussion: Despite these differences, LET does not appear to influence the long-term incidence and composition of IR.
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