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

Abstract

Abstract 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‐γ)‐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%). 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. image

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