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Published on: May 10, 2017
Post-transplant lymphoproliferative disease in children
M H Collins1, K T Montone, A M Leahey
1Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. colv5q@chmcc.org
Insights
Epstein-Barr virus (EBV)-driven post-transplant lymphoproliferative disease (PTLD) in children is a serious complication. Early PTLD (<6 months) is fatal, while later onset (>6 months) offers better survival chances.
Area of Science:
- Pediatric Oncology
- Transplantation Immunology
- Virology
Background:
- Epstein-Barr virus (EBV)-driven post-transplant lymphoproliferative disease (PTLD) significantly impacts pediatric transplant recipients.
- PTLD incidence and outcomes differ between children and adults, with higher frequency in younger patients.
Purpose of the Study:
- To analyze the incidence, outcomes, and diagnostic markers of EBV-driven PTLD in pediatric organ transplant recipients.
- To investigate the correlation between the timing of PTLD onset, EBV serology, and patient survival.
Main Methods:
- Retrospective analysis of 22 pediatric organ transplant recipients diagnosed with PTLD between 1989 and 1998.
- Evaluation of PTLD onset timing (early vs. late post-transplant), EBV serologic status at diagnosis, and survival rates.
- In situ hybridization for EBER1 mRNA to detect EBV in tissue samples.
Main Results:
- PTLD developed in 5% of pediatric transplant recipients, with a mortality rate of 50% (11 of 22).
- Patients developing PTLD <6 months post-transplant had a 100% mortality rate, versus 31% for those diagnosed >6 months post-transplant (p=0.0002).
- Serologic evidence of EBV infection at diagnosis was associated with better survival (91% vs. 25%, p=0.04), and EBER1 mRNA detection was highly sensitive for B-cell PTLD.
Conclusions:
- The timing of PTLD onset post-transplant is a critical prognostic factor in pediatric patients.
- EBV seroconversion can indicate risk but also reflect sufficient immune function for survival.
- In situ hybridization for EBER1 mRNA is a valuable diagnostic tool for EBV-related PTLD.
Abstract:
Epstein-Barr virus (EBV)-driven post-transplant lymphoproliferative disease (PTLD) is an important cause of morbidity and mortality following transplantation, and it occurs more frequently in children than in adults. Of 22 (5%) children at our institution who developed tissue-proven PTLD 1-60 months (mean 16.5 months) following organ transplant, 11 died: nine of these 22 patients developed PTLD between 1989 and 1993, and seven (78%) died; the remaining 13 developed PTLD between 1994 and 1998, and four (31%) died (p = 0.08). All nine patients who developed PTLD < 6 months after transplant died, but 11 of 13 patients who manifested disease > or = 6 months after transplant survived (p = 0.0002). Ten of 11 (91%) survivors, but only two of eight (25%) children who died, had serologic evidence of EBV infection at the time of PTLD diagnosis (p = 0.04). EBV seroconversion identified patients at risk for developing PTLD, but also characterized patients with sufficient immune function to survive EBV-related lymphoid proliferation. In situ hybridization for EBER1 mRNA was diagnostically helpful because it detected EBV in tissue sections of all 20 patients with B-cell PTLD, including those with negative serology.
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