Letermovir Prophylaxis Does Not Hinder Immune Reconstitution While Reshaping Viral Infection Landscape in Children

Background: Letermovir prophylaxis in adults reduces CMV-related morbidity and mortality and may delay T-cell recovery. Pediatric data are limited. Objectives: We aimed to compare absolute counts of CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺, CD19⁺, CD3-CD16⁺CD56⁺ cells on days +60 and +100 after allo-HCT in children managed with pre-emptive therapy (PET) versus those receiving letermovir prophylaxis (LET). Secondary aims were to compare viral outcomes (CMV, EBV, ADV, HHV-6, parvovirus B19, HSV, VZV), within the first 180 days post-HCT in the 2 cohorts. Study design: Retrospective, multicenter study, using propensity score matching to compare letermovir prophylaxis (LET, n = 81) with pre-emptive therapy (PET, n = 81) in children receiving allo-HCT. CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺, CD19⁺, CD3-CD16+CD56⁺ counts on days +60, +100 were measured by flow cytometry. Virological outcomes (CMV, EBV, ADV, HHV-6, parvovirus B19, HSV, VZV) were reported up to day +180. Results: Immune recovery was comparable in both cohorts at each landmark. LET significantly decreased the total number of viral events (45/115 versus 70/115, P = .024), day-90 cumulative incidence of CMV infection (11.1% versus 42%; P < .001), without increasing that of EBV (11.1% versus 18.5%; P = .2). ADV prevailed in LET patients (8 versus 0, P = .006). Viral diseases occurred later under LET (median 58 versus 30 days; P = .018), including 2 EBV-related post-transplant lymphoproliferative disorders (EBV-PTLD), without CMV-disease. Multiple infections were halved (5 versus 17 patients, P = .01). Conclusions: These data show that letermovir does not influence lymphoid reconstitution while markedly reducing CMV burden and reshaping the pediatric post-transplant virological landscape (more ADV and a potential signal for EBV-PTLD).