Prophylactic infusion of donor derived CMV specific T cells for the prevention of CMV reactivation following allogeneic HSCT.

Cytomegalovirus (CMV) reactivation remains a common and serious complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), often leading to significant morbidity and mortality in immunocompromised recipients. Adoptive transfer of CMV-specific cytotoxic T lymphocytes (CMV-CTLs) has emerged as a promising immunotherapeutic approach to restore antiviral immunity and prevent CMV-related complications. This interim analysis of a randomized phase I-II clinical trial evaluates the safety and preliminary efficacy of prophylactic infusion of donor-derived CMV-CTLs administered early after allo-HSCT. Twenty adult allo-HSCT recipients were randomized 1:1 to receive either standard care (control group) or a single intravenous infusion of 10 million donor-derived CMV-CTLs per m2 of body surface area (intervention group) between days + 14 to + 21 post-transplant. The primary endpoint was safety, defined by infusion-related adverse events and incidence of acute graft-versus-host disease (aGvHD). Secondary endpoints included incidence and kinetics of CMV reactivation, measured by serial quantitative RT-PCR during the first 90 days post-transplant. Baseline characteristics were balanced between the two groups. No grade 3-5 adverse events were observed following CMV-CTL infusion. aGvHD grade II occurred in 30% of the intervention group versus 40% in controls. The incidence of CMV reactivation at 90 days was lower in the intervention group (52.00%) compared to controls (77.78%), although not statistically significant (P = 0.580). However, CMV viral loads were significantly lower over time in the intervention group (P = 0.028), suggesting a favorable antiviral effect of CMV-CTLs. Prophylactic infusion of donor-derived CMV-CTLs early after allo-HSCT appears safe and may reduce CMV reactivation and viral burden. These findings support the potential of CMV-CTLs as a novel immunotherapeutic strategy for CMV management in high-risk transplant recipients. Further validation in larger, multicenter trials is warranted.