Epstein-Barr Virus-Induced Posttransplant Lymphoproliferative Disorders

Abstract

Epstein-Barr virus-induced posttransplant lymphoproliferative disease (EBV-PTLD) continues to be a major complication after solid organ transplantation in high-risk patients. Despite the identification of risk factors that predispose patients to develop EBV-PTLD, limitations in our knowledge of its pathogenesis, variable criteria for establishing the diagnosis, and lack of randomized studies addressing the prevention and treatment of EBV-PTLD hamper the optimal management of this transplant complication. This review summarizes the current knowledge of EBV-PTLD and, as a result of two separate international meetings on this topic, and provides recommendations for future areas of study.

De novo malignancies after liver transplantation: A major cause of late death

“…The susceptibility of transplant recipi-ents to the development of lymphomas was first described in 1968. 1 The relationship of these lesions to a viral cause was confirmed when Epstein-Barr virus (EBV) was found to be associated with the majority of PTLD (reviewed in 41 ). Most PTLDs arise within the first 1 to 2 years after transplantation.…”

“…43,44 Of note to this discussion are recent reports of an increased incidence of PTLD in patients with hepatitis C virus coinfection, not only in liver transplant recipients, but in heart transplant recipients, as well 45,46 The pathophysiological course of PTLD is not completely understood. 41 The majority of PTLDs are of B cell origin (Ͼ90%), whereas the remainder is of T cell origin, and only rarely of null cell, i.e., without identifiable T-or B-cell markers. EBV is believed to have a role in the development of the majority of PTLDs, presumably by binding to the EBV-specific receptor found on B cells and providing a growth signal to the infected B cell.…”

“…No clinical trial has delineated which therapeutic approach is best. 41 The potential for exacerbation of rejection with interferon, toxicity with chemotherapy, and logistic problems with cell-based therapy make antibody therapy attractive. With the unavailability of anti-CD21 and anti-CD24 monoclonal antibodies, 48 anti-CD20 monoclonal antibody therapy has been used instead and recently was reported to be of some benefit in post-LT PTLD.…”

Monitoring of Epstein‐Barr virus load after hematopoietic stem cell transplantation for early intervention in post‐transplant lymphoproliferative disease

“…Because of the growing number of high-risk transplantations the incidence of post-transplant lymphoproliferative disease is increasing. Several authors summarized the current knowledge of EBV-induced post-transplant lymphoproliferative disease with regard to the varying incidence, risk factors, heterogeneous clinical presentation, histological findings and treatment modalities [reviews: Purtilo et al, 1992;Savage and Waxman, 1997;Lucas et al, 1997;Paya et al, 1999;Wagner et al, 2002a;Cohen, 2003;Loren et al, 2003;Meerbach et al, 2004]. Post-transplant lymphoproliferative disease can differ clinically from a mononucleosis-like syndrome to malignant lymphoma.…”

Late hepatic allograft dysfunction

“…EBV infection is diagnosed by detecting the presence of EBV virus using PCR technology. 90 In PTLD, the presence of the EBV genome usually signifies active EBV infection. Histologic features of PTLD can be similar to rejection, but a monomorphic mononuclear B-cell lymphocytic portal infiltrate without bile duct damage is highly suggestive of the diagnosis of PTLD.…”