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