Narrative review of chronic active EBV infection—advances in clinical management

Abstract

Chronic active Epstein-Barr virus infection (CAEBV) is a prototype of EBV-associated Tand NK-cell lymphoproliferative diseases (T/NK-cell LPDs). It is a highly progressive disease with fatal organ failure, severe hypercytokinemia [“CAEBV flare”; including hemophagocytic lymphohistiocytosis (HLH)], and overt lymphomatous/leukemic changes. Children and adolescents with CAEBV mostly die within 5–10 years. The progression of adult-onset CAEBV is two-fold faster. We herein present a narrative review. Since CAEBV is a rare disease, limited information is currently available on its treatment. Therefore, we describe our experience of treating CAEBV in addition to a literature review. CAEBV shows a spectrum for its severity and neoplastic nature. Patients will not recover without radical treatment, and mostly require allogeneic hematopoietic stem cell transplantation (HSCT). We established a treatment strategy comprising three steps: cooling [immunochemotherapy with prednisolone (PSL), cyclosporine A (CsA), and etoposide (Etp)], cytoreduction (multidrug-combination block chemotherapy), and reconstruction (allogeneic HSCT). The three-step strategy is applicable to patients at any status of the CAEBV spectrum for improved survival and quality of life. The 3-year overall survival (OS) rate was 76%. Planned HSCT with stable disease or a less active disease status has been successfully performed, and the OS rate is approximately 90%. In contrast, the prognosis of patients with severe disease activity even after chemotherapy is poor (OS rate <20%). Since CAEBV is a progressive disease, the earlier initiation of therapy to complete whole treatment in advance results in better survival. We also discuss new drugs and immunotherapies for CAEBV.