[The road to treating chronic active Epstein-Barr viral infection]

Chronic active Epstein-Barr virus (CAEBV) infection is a progressive disease characterized by persistent inflammatory symptoms accompanied by clonally proliferating EBV-positive T or NK cells. The optimal medical treatment for CAEBV to eradicate EBV-infected T or NK cells has not yet been established, with allogeneic hematopoietic stem cell transplantation as the only strategy currently available. Patients with CAEBV have been reported mainly from limited area of Japan and East Asia. However, CAEBV is drawing a global attention, and the number of reports is increasing worldwide after its definition was added to the EBV-positive T- or NK-cell neoplasms in the 2017 World Health Organization classification. We had previously discovered that STAT3 was constitutively activated in EBV-infected tumor cells in CAEBV inducing the immortalization and production of inflammatory cytokines. Based on these findings, an investigator-initiated clinical research of a JAK1/2 inhibitor ruxolitinib for CAEBV infection was initiated in January 2019. Japanese researchers have been expected to elucidate pathological mechanisms and to establish an effective treatment.