Successful Treatment Using Ebstein Barr Virus-Specific Cytotoxic T-Lymphocytes for Post-Transplant Lymphoproliferative Disorder in Pediatric Small Bowel Transplantation
Fang Kuan Chiou1, Sue Beath1, Darius Mirza1, Khalid Sharif1, Girish Gupte1.
1Liver Unit, Birmingham Children's Hospital, Birmingham, United Kingdom
Introduction: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication following solid organ transplantation and highest incidence is reported in small bowel transplantation (SBTx). Reduction of immunosuppression (RIS), rituximab, and cytotoxic chemotherapy particularly for monomorphic PTLD are therapeutic options but are associated with systemic toxicity, risk of rejection and infection. Adoptive immunotherapy with Ebstein Barr virus-specific cytotoxic T-lymphocytes (EBV-CTL) is an effective treatment but data in pediatric SBTx is scarce.
Aim of the study is to review the outcome and long-term prognosis in pediatric patients who received EBV-CTL therapy for PTLD following SBTx in a tertiary pediatric transplant center.
Method: Retrospective data were collected from medical records of pediatric patients who received EBV-CTL for PTLD following SBTx with or without combined liver transplantation (LTx), identified from a prospectively maintained patient database. PTLD was confirmed on histology based on World Health Organisation (WHO) criteria. The EBV-CTL were third-party sourced, human leucocyte antigen (HLA)-matched and obtained from an accredited national blood transfusion service.
Results: Two patients were identified who underwent combined SBTx and LTx, and received EBV-CTL for PTLD between 1999 and 2001. Their primary disorders were Hirschsprung Disease (patient A) and congenital short bowel syndrome (patient B), both complicated by liver disease. Age at transplantation was 9 and 11 months respectively. Both were EBV seronegative pre-transplant, donor EBV serologies were unknown. Both had history of graft rejection prior to PTLD. Patient A was diagnosed 8 months after transplant with monomorphic PTLD from gastrointestinal (GI) and lymph node biopsies. Patient B was diagnosed 20 months after transplant with monomorphic PTLD in the GI tract. Both had persistent PTLD despite RIS. Both patients subsequently achieved complete histologic and radiologic remission of PTLD following treatment with third-party HLA-matched EBV-CTL with no adverse event. None developed graft-versus-host disease or opportunistic infections. No patient had recurrence of PTLD over 15 years of follow-up.
Conclusion: We report the successful use of third-party HLA-matched EBV-CTL in achieving long-term remission of PTLD in 2 pediatric SBTx patients. EBV-CTL is a safe and effective adjunctive therapy in the treatment of monomorphic PTLD in pediatric SBTx.
 Mynarek M, Schober T, Behrends U, Maecker-Kolhoff B. Posttransplant lymphoproliferative disease after pediatric solid organ transplantation. Clin Dev Immunol. 2013:814973.
 Bollard CM, Rooney CM, Heslop HE. T-cell therapy in the treatment of post-transplant lymphoproliferative disease. Nat Rev Clin Oncol. 2012;9:510-519