Post-transplant lymphoproliferative disorder in children: incidence, prognosis, and treatment options

Abstract

Post-transplant lymphoproliferative disorder (PTLD) after solid organ or hematopoietic stem cell transplantation in children is a serious complication that has been responsible for high mortality rates over recent years. PTLDs are part of a clinically and histologically heterogeneous group of B-lymphocyte proliferations mostly induced by Epstein-Barr virus (EBV) in a context of immunosuppression. Major risk factors for PTLDs in solid organ transplantation are the EBV serostatus mismatch and the intensity, duration, and type of immunosuppression. T-cell depletion and the HLA-mismatched donor and recipient are the main risk factors following hematopoietic stem cell transplantation. For a long time, the only safe and effective therapeutic approach to PTLD was reduction of immunosuppression, with a risk of graft rejection. Based on a better knowledge of the pathophysiology and risk factors for PTLD, preventive and pre-emptive strategies have been recently proposed to control PTLD. New treatment modalities, such as anti-B-cell antibodies, cytokine inhibitor therapy, or anti-EBV cytotoxic T lymphocytes are promising and may improve the outcome of PTLD. These therapeutic approaches need to be further evaluated, especially in the context of pre-emptive strategies adapted to predictive markers of EBV-induced PTLD.