Cytomegalovirus Prophylaxis versus Pre-emptive Strategy: Different CD4+ and CD8+ T Cell Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

Cytomegalovirus-specific T cells restricted for shared and donor human leukocyte antigens differentially impact on cytomegalovirus reactivation risk after allogeneic hematopoietic stem cell transplantation

“…However, late CMV reactivations occur 27,47 , and in the few patients experiencing CMV DNAemia during Letermovir the currently used assays cannot discriminate between non-infective DNA from abortively infected cells and infective virions 48 . Impaired polyclonal T-cell reconstitution and CMVspecific immunity have been recently reported in patients receiving prophylaxis with Letermovir 49,50 . In this context, enumeration of CMV-specific T cells might allow to identify the patients who need to prolong the prophylaxis beyond day 100.…”

Cytomegalovirus infection in transplant recipients: newly approved additions to our armamentarium

“…Further, letermovir was associated with lower healthcare costs in CMV-seropositive adult HCT recipients, derived in part from the shorter length of stay, lower re-hospitalization rates, mortality benefit, and increased life expectancy compared with control groups (24)(25)(26)(27)(28). However, letermovir prophylaxis may be associated with delayed T-cell reconstitution at days +60 and +90, and higher incidence of CMV reactivation after discontinuation at day +100, as seen in a phase III trial (19) and a small retrospective study comparing PET to letermovir prophylaxis (29). Furthermore, Zamora et al (30) showed that polyfunctional T-cell responses to IE-1 and pp65 at 3 months after allogeneic HCT were decreased in recipients of letermovir prophylaxis, despite adjustment for donor CMV serostatus, absolute lymphocyte count, and steroid use.…”

“…Furthermore, Zamora et al (30) showed that polyfunctional T-cell responses to IE-1 and pp65 at 3 months after allogeneic HCT were decreased in recipients of letermovir prophylaxis, despite adjustment for donor CMV serostatus, absolute lymphocyte count, and steroid use. These findings suggest that a longer duration of letermovir prophylaxis, i.e., beyond day +100 post-HCT, may be necessary in patients with delayed CMV T-cell reconstitution (19,29,30). A randomized clinical trial investigating the safety and efficacy of letermovir beyond day +100 post-allo-HCT is ongoing (NCT03930615).…”

Challenges and Opportunities in Antimicrobial Stewardship among Hematopoietic Stem Cell Transplant and Oncology Patients

“…Cesaro et al surveyed treatment approaches to CMV infection in a 2020 survey among European BMT centers, highlighting that up to 62% of centers are adopting a prophylaxis-based approach with letermovir [ 66 ]. Different strategies and the impact of letermovir prophylaxis on CMV reactivation are being studied [ 63 , 67 , 68 ].…”