The diversity of cytomegalovirus among blood donors and transplant recipients could affect the effectiveness of specific anti-CMV immunoglobulins

Introduction: Human cytomegalovirus (CMV) remains a major cause of morbidity and mortality in pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT), where its high genetic variability and the limitations of current antiviral therapies pose significant clinical challenges. Despite standard antiviral prophylaxis, CMV infection affects up to 80% of allo-HSCT recipients, necessitating the evaluation of alternative strategies to overcome the limitations of conventional treatments. This single-center ambispective study investigates the application of CMV-specific immunoglobulin (Ig) prophylaxis, focusing on its impact on viral clearance, transplant outcomes, immunological readouts, and efficacy across diverse ethnic cohorts (European vs. non-European). Methods: A post hoc analysis was performed on 71 hematopoietic stem cell recipients who received CMV-specific Ig (Study Group) and historical controls (Control Group). A pharmacokinetic analysis was performed on the Study Group. Results: The Control Group exhibited higher rates of first-blood CMV DNA detection post-transplant (p = 0.0024), second-blood CMV DNA detection post-transplant (p = 0.00042), CMV DNA viral load (p = 0.0016), reduced hospital stays (p = 0.007) and improved immune reconstitution (p < 0.0001). No significant differences in hospital stay emerged between European and non-European patients. However, Europeans had better results in first-blood CMV DNA detection (p = 0.006), second reactivation (p = 0.00032), immune reconstitution at day +90 (p = 0.0443), clearance rates, and reduced need for second-line therapy (p < 0.001). The terminal half-life of CMV-specific Ig was approximately 15 days. Discussion: These findings demonstrate that CMV-specific Ig serves as an effective molecular immunotherapy, significantly improving immunological readouts and clinical outcomes in pediatric allo-HSCT. Furthermore, the observed ethnic disparities underscore the importance of personalized molecular strategies to address CMV genome variability and global health challenges.