Immunotherapeutic options for Epstein-Barr virus-associated lymphoproliferative disease following transplantation

Epstein-Barr virus-associated lymphoproliferative diseases (EBV-LPD) after hematopoietic stem cell transplantation or solid-organ transplantation remain a serious and potentially life-threatening complication. In the last decade, outcomes for EBV-LPD have significantly improved. Key to this success was the development of early detection methods, such as serial measurements of EBV-DNA load in the peripheral blood of transplant recipients. Immunotherapeutic interventions for EBV-LPD include reduction of immunosuppression, CD20 monoclonal antibodies (rituximab) as monotherapy or in conjunction with chemotherapy, and adoptive immunotherapy with EBV-specific T cells. Pre-emptive immunotherapeutic interventions can prevent the development of EBV-LPD. As monotherapy, immunotherapy is effective in inducing remissions of EBV-LPD with low-risk features. For high-risk disease, combining immunotherapy with conventional therapies has led to superior outcomes. Current challenges consist of risk stratifying patients so that patients receive the most efficacious therapy without suffering from unwanted side effects.