Subtype-specific progression of post-transplant lymphoproliferative disease (PTLD) in children: Implications for age-based surveillance and early intervention strategies.

Post-transplant lymphoproliferative disorder (PTLD) represents a major cause of mortality in pediatric liver transplant recipients. However, data on clinicopathological risk factors across its subtypes remain limited. An analysis of 33 pediatric liver transplant recipients revealed significant differences in the time to onset among PTLD subtypes: monomorphic PTLD developed significantly later than non-destructive/polymorphic PTLD, with higher tacrolimus blood concentration at diagnosis in the latter, consistent with the immunosuppressive tapering protocols. Among monomorphic PTLD cases, patients with Burkitt lymphoma (BL-PTLD) had a younger transplant age and higher early tacrolimus blood concentration than those with diffuse large B-cell lymphoma (DLBCL-PTLD), indicating that younger transplant age and more intense immunosuppression may promote Burkitt lymphomagenesis. Notably, among monomorphic PTLD, patients transplanted at <1 year showed a significantly prolonged interval from transplantation to diagnosis than those transplanted at 1-18 years. Universal EBV-encoded RNA (EBER) positivity confirmed Epstein-Barr virus (EBV) as a key pathogenic factor, while the blood EBV DNA load at diagnosis showed no significant differences across subtypes, suggesting it does not influence PTLD subclassification. These findings suggest that the time interval from transplantation to PTLD, immunosuppression intensity, and age at liver transplantation play a more determinant role in PTLD subtype progression.