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Rational management of posttransplant lymphoproliferative disorder in pediatric recipients
K Praghakaran1, B Wise, A Chen
1Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Insights
Aggressive management of posttransplant lymphoproliferative disorder (PTLD) in pediatric liver transplant patients, including immunosuppression withdrawal and chemotherapy, resulted in 100% survival. This approach is crucial for managing this potentially lethal Epstein-Barr virus (EBV)-related complication.
Area of Science:
- Pediatric transplantation
- Immunology
- Oncology
Background:
- Posttransplant lymphoproliferative disorder (PTLD) is a severe complication in pediatric transplant recipients, often linked to Epstein-Barr virus (EBV) and intense immunosuppression.
- PTLD affects up to 10% of pediatric transplant recipients, with a high mortality rate of up to 80%.
Purpose of the Study:
- To report the diagnostic experience and evaluate the efficacy of an aggressive, sequential management strategy for PTLD in pediatric liver transplant patients under age 5.
- To assess patient and graft survival rates following this intensive treatment protocol.
Main Methods:
- A review of 75 pediatric liver transplant recipients identified five biopsy-proven PTLD cases managed with a sequential "intent-to-treat" approach.
- Initial management involved immunosuppression withdrawal, followed by chemotherapy (cyclophosphamide, vincristine, Adriamycin, intrathecal methotrexate/ara-C) for progressive disease.
Main Results:
- All five pediatric patients diagnosed with PTLD achieved complete remission and survived, with a mean follow-up of 29 months.
- Three patients experienced graft rejection requiring immunosuppression reintroduction; two are now maintained on low-dose prednisone without FK-506.
- One patient developed central nervous system lymphoma with neurological sequelae.
Conclusions:
- Early immunosuppression withdrawal combined with aggressive chemotherapy is effective in achieving 100% patient and graft survival in pediatric liver transplant recipients with PTLD.
- This aggressive strategy offers a viable treatment option for PTLD, a life-threatening condition in this vulnerable population.
Background/Purpose:
Posttransplant lymphoproliferative disorder (PTLD) is a potentially lethal complication in the pediatric transplant patient secondary to Epstein-Barr virus (EBV) infection and potent immunosuppression. PTLD may develop in up to 10% of pediatric transplant recipients with mortality rates up to 80%. The authors report their experience with the diagnosis and efficacy of aggressive sequential management of PTLD in five patients under age 5 years.
Methods:
A review of 75 pediatric liver transplant recipients on FK-506-based immunosuppression identified five biopsy-proven cases of PTLD and one probable case (8%). The probable case was a teenager, 6 months posttransplant in Spain, with mediastinal masses. No treatment or diagnosis was sought, and the patient died. The other five cases were managed with sequential therapy on an "intent-to-treat" basis with initial withdrawal of immunosuppression. If the disease progressed, patients were treated with four courses of intravenous cyclophosphamide, vincristine, Adriamycin, and intrathecal methotrexate and ara-C.
Results:
Five children were anti-EBV titer negative at the time of transplant. Three of five received EBV-positive donor organs and two children received EBV-negative livers. Monoclonal PTLD developed between 2 and 31 months posttransplant (mean, 15.7 months). With onset of PTLD (four B cell lymphoma, one B cell leukemia) all patients had tapering or withdrawal of immunosuppression and initiation of highdose acyclovir. Two of five patients had complete remission and resumed immunosuppression. Two patients progressed and required chemotherapy. One patient with initial response relapsed 4 months later with B cell leukemia and required chemotherapy. All five patients are alive 10 to 38 months postdiagnosis (mean, 29 months). Three patients had rejection requiring resumption of FK-506 therapy. Two patients are maintained on low-dose alternate-day prednisone and no FK-506. All patients have normal liver function. Central nervous system lymphoma developed in one child with significant neurological sequelae.
Conclusions:
PTLD can develop in pediatric liver transplant recipients. Early withdrawal of immunosuppression and aggressive chemotherapy enabled us to achieve 100% patient and graft survival.