Recent Advances in Adult Post-Transplant Lymphoproliferative Disorder

Simple Summary Post-transplant lymphoproliferative disorder (PTLD) is a potentially life-threatening complication of mainly solid organ and, less frequently, allogeneic hematopoietic stem-cell transplantation, with a reported incidence of 2 to 20%. PTLD has a complex pathogenesis and not all aspects are well understood to date; however, a proportion of cases are strongly related to Epstein-Barr virus. Therapy mainly depends on the histologic subtype; however, the heterogeneity of the disease and lack of clinical trials create gaps in evidence-based management of these patients. In this review, we discuss the pathogenesis, classification, and risk factors of PTLD. We further analyze common treatment strategies and describe the latest advances in disease management and prevention, including novel therapies. PTLD is a rare but severe complication of hematopoietic or solid organ transplant recipients, with variable incidence and timing of occurrence depending on different patient-, therapy-, and transplant-related factors. The pathogenesis of PTLD is complex, with most cases of early PLTD having a strong association with Epstein-Barr virus (EBV) infection and the iatrogenic, immunosuppression-related decrease in T-cell immune surveillance. Without appropriate T-cell response, EBV-infected B cells persist and proliferate, resulting in malignant transformation. Classification is based on the histologic subtype and ranges from nondestructive hyperplasias to monoclonal aggressive lymphomas, with the most common subtype being diffuse large B-cell lymphoma-like PTLD. Management focuses on prevention of PTLD development, as well as therapy for active disease. Treatment is largely based on the histologic subtype. However, given lack of clinical trials providing evidence-based data on PLTD therapy-related outcomes, there are no specific management guidelines. In this review, we discuss the pathogenesis, histologic classification, and risk factors of PTLD. We further focus on common preventive and frontline treatment modalities, as well as describe the application of novel therapies for PLTD and elaborate on potential challenges in therapy.