Current Diagnosis and Treatment Strategy for Chronic Active Epstein-Barr Virus Infection

Abstract

Chronic active EBV infection (CAEBV) is a representative disease amongst a spectrum of EBV-associated T/NK-cell lymphoproliferative disease (LPD), with recently proposed diagnostic guidelines as follows; (1) persistent or recurrent infectious mononucleosis-like symptoms such as fever, swelling of lymph nodes, and hepatosplenomegaly, (2) an unusual pattern of anti-EBV antibodies with elevated levels of anti-viral capsid antigen and anti-early antigen, and/or evidence of increased EBV genome number in affected tissues, including the peripheral blood, (3) chronic illness which cannot be explained by other known disease processes at diagnosis. The prognosis of patients with CAEBV is very poor in both pediatric and adult patients. In the absence of effective therapy, almost all patients will die within 5–15 years from onset because of hepatic or cardiac failure, hemophagocytic syndrome, malignant lymphoma, opportunistic infections, or intracranial/gastrointestinal bleeding. To-date, investigational therapies for CAEBV have comprised immunore­gulatory drugs and antiviral agents, all resulting in disappointing outcomes. Eleven years ago we sought to investigate a new therapeutic algorithm for CAEBV comprising sequential immunochemotherapy, combination chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in an attempt to reduce and/or eliminate EBV-infected T/NK cells.