Cytomegalovirus-specific T-cell reconstitution following letermovir prophylaxis after hematopoietic cell transplantation

作者：Danniel Zamora, Elizabeth R. Duke, Hu Xie, Bradley C. Edmison, Brenda Akoto, Richard Kiener, Terry Stevens‐Ayers, Ralf Wagner, Marco B. Mielcarek, Wendy M. Leisenring, Keith R. Jerome, Joshua Tisdell Schiffer, Greg Finak, Stephen C. De Rosa, Michael Boeckh · 发表于：Blood · 年份：2021 · DOI：10.1182/blood.2020009396 · 被引用次数：171 · 研究领域：Cytomegalovirus and herpesvirus research、Herpesvirus Infections and Treatments、Toxoplasma gondii Research Studies

Decreased cytomegalovirus (CMV)-specific immunity after hematopoietic cell transplantation (HCT) is associated with late CMV reactivation and increased mortality. Whether letermovir prophylaxis-associated reduction in viral exposure influences CMV-specific immune reconstitution is unknown. In a prospective cohort of allogeneic HCT recipients who received letermovir, we compared polyfunctional CMV-specific T-cell responses to those of controls who received PCR-guided preemptive therapy before the introduction of letermovir. Thirteen-color flow cytometry was used to assess T-cell responses at 3 months after HCT following stimulation with CMV immediate early-1 (IE-1) antigen and phosphoprotein 65 (pp65) antigens. Polyfunctionality was characterized by combinatorial polyfunctionality analysis of antigen-specific T-cell subsets. Use of letermovir and reduction of viral exposure were assessed for their association with CMV-specific T-cell immunity. Polyfunctional T-cell responses to IE-1 and pp65 were decreased in letermovir recipients and remained diminished after adjustment for donor CMV serostatus, absolute lymphocyte count, and steroid use. Among letermovir recipients, greater peak CMV DNAemia and increased viral shedding were associated with stronger CD8+ responses to pp65, whereas the CMV shedding rate was associated with greater CD4+ responses to IE-1. In summary, our study provided initial evidence that letermovir may delay CMV-specific cellular reconstitution, possibly rel...