Solid organ transplantation (SOT) is an effective treatment modality for children and young adults with end-stage organ failure with 5-year overall survival ranging from 39 to 96% depending on the transplanted organ [1]. Patients subsequently require lifelong treatment with immunosuppressive medications to maintain graft health and limit the risk of graft rejection [2]. Commonly used immunosuppressants to inhibit organ recipient T-lymphocyte function include calcineurin inhibitors (CNI), mTOR inhibitors, thiopurines, and antimetabolites [3]. A byproduct of this induced T-cell immunosuppression is some degree of deficiency in anti-viral response and surveillance of virally transformed cells including pre-malignant and malignant states [4].

Post-transplant lymphoproliferative disorder (PTLD) includes a broad and heterogeneous group of disorders, ranging from indolent and non-malignant lymphoproliferations to malignant lymphomas. More than 70% of cancers diagnosed in pediatric SOT recipients are PTLD. Compared to the general population, the incidence of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma is 212 times and 19 times higher, respectively [5]. Most pediatric cases consist of B-lymphocytes of host origin infected with the Epstein-Barr virus (EBV) [6]. PTLD occurring after hematopoietic stem cell transplantation (HSCT) generally occurs prior to T-cell reconstitution [7] but is outside the scope of this review.

Due to the rarity of PTLD and the heterogeneous nature of the disease, multi-center prospective pediatric studies are uncommon. This review focuses on the workup and management of PTLD, discussion of novel therapy options and opportunities for research.