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Meeting the Challenges of Post-Transplant Lymphoproliferative Disorders After Liver Transplantation in Children: A
Nathalie Marie Rock1,2, Antonin Bouroumeau3,4, Danai Papangelopoulou5,6
1Swiss Pediatric Liver Center, Department of Pediatrics, Gynecology, and Obstetrics, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
Insights
Post-transplant lymphoproliferative disorders (PTLD) in pediatric liver transplant (LT) patients are challenging. A new diagnostic and management algorithm, considering biopsy heterogeneity, has been developed.
Area of Science:
- Pediatric Oncology
- Transplantation Immunology
- Hematology
Background:
- Post-transplant lymphoproliferative disorders (PTLD) pose significant risks to pediatric solid organ transplant (SOT) recipients.
- Accurate diagnosis and effective management of PTLD in children present considerable challenges.
Purpose of the Study:
- To analyze a pediatric liver transplant (LT) cohort to address diagnostic and management challenges of PTLD.
- To develop a diagnostic and management algorithm for PTLD in pediatric LT recipients.
Main Methods:
- Retrospective review of pediatric LT recipients with suspected Epstein-Barr virus (EBV)-driven PTLD from 2009-2021.
- Classification of cases using the World Health Organization (WHO) 2022 criteria for Pediatric Tumors, defining histologically confirmed and 'indeterminate PTLD' groups.
- Utilized (18F) fluorodeoxyglucose PET/CT for biopsy guidance.
Main Results:
- 111 pediatric LT recipients were included; 13 (11.7%) had confirmed PTLD, and 3 were in the 'indeterminate' group.
- Non-destructive PTLD was the most common subtype (6/13), followed by monomorphic (4/13) and polymorphic (3/13).
- (18F)FDG PET/CT guided biopsies in 11/13 patients. Nine patients were successfully treated with mTOR inhibitors.
Conclusions:
- A diagnostic and management algorithm for pediatric PTLD in LT recipients was developed based on this cohort analysis.
- Recognizing spatial and temporal heterogeneity is crucial, supporting multiple or repeated biopsies at diverse sites.
- mTOR inhibitors demonstrated a favorable safety profile in this cohort.
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.
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