This study investigates the impact of letermovir prophylaxis on viral infections (including CMV, EBV, BKV, HHV-6/7, RSV, ADV, HSV, etc.) following allogeneic hematopoietic stem cell transplantation in pediatric patients with EBV-associated T/NK-cell lymphoproliferative diseases and refractory/relapsed EBV-related hemophagocytic lymphohistiocytosis. Additionally, we examine its effects on other transplantation complications, including engraftment failure, graft-versus-host disease (GvHD), disease relapse, thrombotic microangiopathy (TMA), overall survival (OS), post-transplant lymphoproliferative disorder (PTLD) incidence, and immune reconstitution.
Diagnosed with EBV-positive T/NK lymphoproliferative disease (EBV-T/NK LPD) according to ICC 2022 criteria, or diagnosed with refractory/relapsed EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) according to the 2004-HLH diagnostic criteria;
Undergoing first allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the study center;
Age < 18 years;
CMV seropositive (IgG+) prior to transplantation;
History of CMV end-organ disease within 6 months prior to enrollment;
Severe hepatic dysfunction (defined as Child-Pugh Class C);
End-stage renal impairment with creatinine clearance < 10 mL/min (calculated by Cockcroft-Gault equation);
Prior allogeneic hematopoietic stem cell transplantation;
Parallel
Letermovir
DrugArm 1 (Letermovir Prophylaxis): Pediatric patients receive oral letermovir once daily from day 0 to day 100 post-transplant. Prophylaxis may be extended to day 200 if high-risk factors persist (steroid use, poor immune reconstitution). Dosing: 480mg (≥30kg), 240mg (15-30kg), 120mg (7.5-15kg), 80mg (6-7.5kg); halved if co-administered with cyclosporine. Arm 2 (Control): Historical control cohort (2018-2023) receiving no routine CMV prophylaxis; preemptive therapy with ganciclovir/foscarnet initiated only when plasma PCR exceeds threshold.
Incidence of Clinically Significant CMV Infection (cs-CMVi) and EBV Infection (cs-EBVi)
To evaluate the incidence of clinically significant CMV and EBV infections in pediatric patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with or without letermovir prophylaxis.
Incidence of Other Viral Infections and Transplant-Related Complications
To assess the incidence of other viral infections (e.g., BKV, HHV-6/7, RSV, ADV, HSV), graft-versus-host disease (GvHD), post-transplant lymphoproliferative disorder (PTLD), thrombotic microangiopathy (TMA), graft failure, relapse, overall survival (OS), and immune reconstitution (T/B/NK cell counts and function).
Safety and Tolerability of Letermovir in Pediatric allo-HSCT Recipients
To monitor adverse events (AEs) and serious adverse events (SAEs) related to letermovir prophylaxis, including gastrointestinal symptoms, liver function abnormalities, cardiac events, and other treatment-emergent AEs.
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