This review aims to show new insights into the prevention and management of cytomegalovirus (CMV) infections in pediatric hematopoietic stem cell transplant (HCT) recipients. CMV-seropositivity in pediatric recipients/donors (R/D) is lower than in adults. Post-HCT CMV infection rates appear to follow the hierarchy: R+/D- > R+/D+ > R-/D+. Pediatric risk factors are similar to those seen in adults and include recipient CMV-seropositivity, HCT from an alternative donor, older age, and graft-versus-host-disease. In case of CMV-seropositive pediatric recipients, donor CMV-seronegativity is associated with lower survival and higher non-relapse mortality. Until recently, preemptive treatment has been the standard approach for managing pediatric post-HCT CMV infection. The successful introduction of letermovir in the prophylaxis of CMV infection has changed this approach and has become the standard of care in adults. Clinical data and recent FDA/EMA approval of letermovir in children are also providing a breakthrough in pediatric CMV disease prevention. Pre-emptive treatment remains the preferred approach in case of clinically significant CMV infection in both adults and children; meanwhile, new available options such as maribavir and broader application of viral-specific T-cells represent valid strategies for the management of refractory/resistant CMV infection, offering a less-toxic therapeutic alternative to conventional, still effective, antivirals.
© 2025. The Author(s), under exclusive licence to Springer Nature Limited.