Epstein-Barr virus-associated lymphoproliferative disorders in immunosuppressed patients

Abstract

: A diverse range of Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPDs) arise in the context of immunodeficiency. Post-transplant lymphoproliferative disease (PTLD) encompasses multiple disease entities which develop due to iatrogenic immunosuppression necessary for organ transplantation, and are frequently EBV-positive. A similar spectrum of lymphoproliferative pathologies, many of which are EBV-associated, occur in non-transplant immunodeficiency states, including those secondary to disease-modifying agents, human immunodeficiency virus (HIV) infection, age-associated immunosenescence, and a wide array of primary immune conditions. Common to each of these disease settings is disruption of the normal immune responses that exert control over EBV, permitting the virus to contribute to tumourigenesis. In this review, we provide an overview of the classification of EBV-positive immunodeficiency-associated LPDs, highlighting the strengths and weaknesses of systems provided by the World Health Organisation (WHO) Classification of Tumours of Haematopoietic and Lymphoid Tissues in comparison to the Society for Hematopathology (SH) and the European Association for Haematopathology (EAH). As an exemplar of EBV-associated LPD, we then undertake a detailed review of the pathophysiology and management of PTLD. This includes a discussion of prophylactic, pre-emptive and therapeutic approaches, recognising important differences in the management of PTLD arising after haematopoietic stem cell and solid organ transplantation. We summarise recent published clinical data guiding the use of conventional chemo-immunotherapy, and cover the role of cellular and novel drug therapies. Thereafter, we provide focused reviews on a selection of other noteworthy EBV-positive LPD entities, highlighting current and emerging strategies for their management: EBV-positive mucocutaneous ulcer, EBV-positive diffuse large B-cell lymphoma, plasmablastic lymphoma, primary effusion lymphoma and lymphomatoid granulomatosis.