Dorota Broniszczak-Czyszek, Poland
Attending doctor
Department of Pediatric Surgery and Organ Transplantation
Children's Memorial Health Institute
Complete withdrawal of immunosuppression and long-term graft function in pediatric liver recipients who developed PTLD or EBV infection
Dorota Broniszczak-Czyszek1, Małgorzata Markiewicz1, Marek Szymczak1, Joanna Teisseyre1, Maria Janowska1, Julita Latka-Grot 1, Marek Stefanowicz 1, Bożenna Dembowska-Bagińska 2, Anna Wakulińska2, Sylwia Szymańska3, Barbara Piątosa4, Piotr Kaliciński1.
1Pediatric Surgery and Organ Transplantation, Children's Memorial Health Institute, Warsaw, Poland; 2Oncology, Children's Memorial Health Institute, Warsaw, Poland; 3Department of Pathology , Children's Memorial Health Institute, Warsaw, Poland; 4Histocompatibility Laboratory, Children's Memorial Health Institute, Warsaw, Poland
Introduction: The study aimed to assess the long-term outcome in pediatric patients who underwent liver transplantation (LTx) and developed PTLD or EBV infection after discontinuation of immunosuppressive therapy (IS).
Material and methods: A retrospective, single-center study was conducted involving 32 pediatric patients who received LRdLT (15 pts) or DdLTx (7 pts) and who had their immunosuppression discontinued due to the development of PTLD (29 pts) or active EBV infection (3 pts). Their age ranged from 5 to 211 months (median 11 months) at the time of transplant, with 81% of patients being under 2 years old. Six patients received an ABO-incompatible graft. The incidence, timing, severity, and reversibility of acute rejection (AR) episodes, as well as graft and patient outcomes, were assessed after the complete withdrawal of IS. In patients who are no longer receiving immunosuppressive therapy, liver function was evaluated by liver labs, graft biopsies, and the presence of donor-specific antibodies (DSA).
Results: In 12 patients, IS withdrawal lasted from 1 to 41 months (median 8 months) and was restored due to AR (mild or moderate) or cessation of EBV infection. All patients with AR responded positively to steroids or low-dose calcineurin inhibitors/MMF. All these patients returned to baseline graft function. Two patients required retransplantation due to biliary complications late after LT. No patient lost graft function due to chronic rejection.
Among 20 patients remaining off immunosuppressive therapy, one patient died of lymphoma 12 months after diagnosis; the remaining 19 patients maintained normal graft function for a median of 79 months (range 33 - 86 months). Follow-up biopsies showed no significant changes compared to baseline biopsies, with low-grade fibrosis noted in some patients. Donor-specific antibodies were detected in 11 patients, while they were not present in 5 patients.
Conclusions: PTLD management, including early cessation of immunosuppressive therapy, is recommended. Episodes of rejection after immunosuppression withdrawal can be effectively treated with standard therapies without resulting in graft loss. Most pediatric patients who discontinued immunosuppressive therapy due to PTLD/EBV successfully maintain normal graft function without immunosuppression, with stable liver histology. However, monitoring of DSA levels is recommended.