Journal Article DKFZ-2026-01401

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Letermovir does not affect long-term polyclonal immune reconstitution after allogeneic hematopoietic stem cell transplantation with ATG-based GvHD prophylaxis.

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2026
Frontiers Media Lausanne

Frontiers in immunology 17, 1790563 () [10.3389/fimmu.2026.1790563]
 GO

Abstract: 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.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.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.Despite these differences, LET does not appear to influence the long-term incidence and composition of IR.

Keyword(s): allogeneic stem cell transplantation ; human cytomegalovirus ; immune reconstitution ; letermovir ; pre-emptive treatment

Classification:

Contributing Institute(s):
  1. Biostatistik (C060)
Research Program(s):
  1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2026
Database coverage:
Medline ; Creative Commons Attribution CC BY (No Version) ; DOAJ ; Article Processing Charges ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2026-06-09, last modified 2026-06-10


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