Meeting the Challenges of Post-Transplant Lymphoproliferative Disorders After Liver Transplantation in Children: A Proposed Diagnostic and Management Algorithm.

BACKGROUND

Post-transplant lymphoproliferative disorders (PTLD) may significantly impair outcomes in children after solid organ transplantation (SOT). Diagnosis and treatment may be challenging. We analyze a representative pediatric liver transplant (LT) cohort in light of these challenges.

METHODS

Pediatric LT recipients monitored by the Swiss Pediatric Liver Center from 2009 to 2021 with a suspicion of Epstein-Barr virus (EBV) driven PTLD were included. All cases were retrospectively reviewed using the World Health Organization (WHO) 2022 classification criteria for Pediatric Tumors. Two groups were defined: (1) histologically confirmed PTLD, and (2) 'indeterminate PTLD' if criteria were not entirely met.

RESULTS

During the inclusion period, 111 patients underwent LT. Histology review confirmed PTLD in 13 patients (11.7%) while 3 patients were included in the 'indeterminate' group. The most common subtype was non-destructive PTLD (6/13), followed by monomorphic (4/13) and polymorphic PTLD (3/13). Hypermetabolism on whole body (18F) fluorodeoxyglucose PET/CT helped define adequate biopsy location in 11/13 patients. Three patients with monomorphic PTLD also showed low-grade PTLD subtypes in other biopsy sites. Nine patients received mTOR inhibitors after diagnosis, either as monotherapy or in combination with calcineurin inhibitors, without major side effects.

CONCLUSIONS

The detailed analysis of our series of pediatric LT patients with PTLD allowed for the development of a diagnostic and management algorithm, now applied at our institution. Spatial and temporal heterogeneity argues in favor of multiple and, if necessary, repeated biopsies at different sites.