Features of cytomegalovirus DNAemia and virus-specific T-cell responses in allogeneic hematopoietic stem-cell transplant recipients during prophylaxis with letermovir

Background: There is scarce information on the natural kinetics of cytomegalovirus (CMV) DNAemia and dynamics of CMV-specific T-cell reconstitution in allogeneic hematopoietic transplant recipients (allo-HSCT) undergoing letermovir (LMV) prophylaxis.Methods: Twelve adult CMV-seropositive high-risk recipients (median age, 53 years; 9 males/3 females) undergoing LMV prophylaxis and 13 non-LMV allo-HSCT controls (median age, 58 years; 7 males/6 females) were included. CMV DNAemia in plasma was monitored by real-time polymerase chain reaction. Preemptive antiviral therapy (PET) was administered upon detection of >= 1500 IU/ml. CMV-specific interferon-gamma (IFN-gamma)-producing CD8(+) and CD4(+) T cells were enumerated by flow cytometry around days +30, +60, and +90 after allo-HSCT. Ex vivo experiments assessing of the potential effect of LMV on CMV-specific T-cell expansion in a single CMV-seropositive donor were also conducted.Results: Five LMV patients (41.6%) developed CMV DNAemia that cleared spontaneously. Four patients (33.3%) developed CMV DNAemia after LMV cessation, of which two required PET. Nine non-LMV patients (69.2%) developed CMV DNAemia (five required PET). The percentage of LMV and non-LMV patients exhibiting detectable CMV-specific T-cell responses was comparable (7/10 vs. 10/13; p = .71). Nevertheless, median CMV-specific CD4(+) and CD8(+) T-cell counts were lower in LMV patients by days +60 (p = .006 and .02, respectively) and +90 (p = .08 and .02). Ex vivo, CMV-specific CD8(+) T cells expanded to the same level either in the presence (19.8%) or in the absence of LMV (20.6%).ConclusionsIn our series, episodes of CMV DNAemia in LMV patients cleared spontaneously. A diminished degree of CMV-specific T-cell reconstitution in LMV patients compared to non-LMV patients was observed.Conclusions: In our series, episodes of CMV DNAemia in LMV patients cleared spontaneously. A diminished degree of CMV-specific T-cell reconstitution in LMV patients compared to non-LMV patients was observed.

Automated summary

There is limited information on the natural kinetics of CMV DNAemia and CMV-specific T-cell reconstitution in allo-HSCT recipients undergoing LMV prophylaxis. This study found that CMV DNAemia cleared spontaneously in a high proportion of LMV patients, and LMV patients had a lower degree of CMV-specific T-cell reconstitution compared to non-LMV patients.