Incidence and risk factors of Epstein-Barr virus infection and post-transplant lymphoproliferative disorder in paediatric haploidentical allogeneic hematopoietic stem cell transplantation.

Epstein-Barr virus (EBV) reactivation after haploidentical stem cell transplant (haplo-HSCT) is a serious complication, which sometimes progresses to post-transplant lymphoproliferative disorder (PTLD). We retrospectively analyzed 448 pediatric patients ( ≤ 18 years) undergoing anti-thymocyte globulin (ATG)-based haplo-HSCT with letermovir prophylaxis at Peking University People's Hospital (Oct 2022-Oct 2025), using a 1:3 propensity score-matched design. EBV viremia and PTLD incidences were 12.4% and 4.9%. Multivariate analysis showed prior Chimeric Antigen Receptor (CAR) T-cell therapy (Hazard ratio (HR) = 2.040, 95% CI 1.061-3.920; p = 0.033) and Cytomegalovirus (CMV) viremia preceding EBV viremia (HR = 6.075, 95% CI 3.377-10.928; p < 0.001) were risk factors for EBV viremia. The PTLD risk was higher with a total body irradiation (TBI)-based conditioning regimen (HR = 1.917, 95% CI 0.980-3.750; p = 0.050). Overall survival did not differ between groups (EBV + : 92.9% vs. EBV-: 96.4%; p = 0.10), but event-free survival was inferior in EBV-infected patients (86.6% vs. 94.6%; p = 0.004). Chronic graft-versus-host disease (17.0% vs. 6.5%; p < 0.001) and transplant-related mortality (7.1% vs. 2.1%; p = 0.005) were significantly higher in the EBV viremia cohort. EBV reactivation and PTLD pose serious challenges, and risk factors include TBI conditioning, prior CAR-T therapy, and CMV viremia preceding EBV viremia. Preemptive cytotoxic T lymphocyte therapy may benefit high-risk patients.