Letermovir prophylaxis timing in standard-risk and very high-risk adult CMV-seropositive allogeneic hematopoietic stem cell transplant recipients: A systematic literature review.

Cytomegalovirus (CMV) infection remains a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We conducted a systematic review of 34 studies including 3489 CMV-seropositive adult allo-HSCT recipients who received prophylaxis initiated within 28 days post-transplantation. Across studies, the reported median initiation time ranged from day 0 to day 21, with most studies (69.7%) initiating within the first 7 days. Among studies evaluating standard-risk patients, those reporting earlier initiation (<7 days) tended to report lower ranges of clinically significant CMV infection (cs-CMVi) at commonly reported follow-up horizons, including day 100 (0-23.7% vs. 14-28%), day 200 (10.7-31.7% vs. 17.5-56%), and 1 year (17.8-43.5% vs. 38.7-56.0%), compared with studies reporting later initiation. Early initiation was also associated with lower reported ranges of CMV reactivation by day 100. In studies including very high-risk patients, early median initiation was associated with lower reported cs-CMVi incidence in the early post-transplant period, although this pattern was not consistently observed at later follow-up time points. Considerable heterogeneity in patient populations, prophylaxis duration, and monitoring strategies across studies precluded quantitative synthesis. In summary, this descriptive systematic review highlights practice patterns and directional trends suggesting potential benefits of earlier letermovir initiation in standard-risk allo-HSCT recipients, while underscoring the need for individualized strategies and further prospective evaluation in very high-risk populations. REGISTRATION: PROSPERO (CRD42024573330).