Nationwide survey of systemic chronic active EBV infection in Japan in accordance with the new WHO classification

Abstract

Systemic chronic active Epstein-Barr virus infection (sCAEBV) was defined as a T- or NK-cell neoplasm in the 2017 World Health Organization (WHO) classification. To clarify the clinical features of sCAEBV under this classification and review the effects of chemotherapy, we performed a nationwide survey in Japan from 2016 through 2018 of patients with sCAEBV newly diagnosed from January 2003 through March 2016. One hundred cases were evaluated. The patients were aged 1 to 78 years (median, 21) and included 53 males and 47 females. Spontaneous regression was not observed in patients with active disease. In the childhood-onset group (age, <9 years), 78% of the patients were male. In contrast, 85% of the patients in the elderly-onset group (age, >45 years) were female. The prognosis of the childhood-onset group was better than those of the adolescent/adult- and elderly-onset groups. The main chemotherapies used were a combination of cyclosporine A, steroids, and etoposide (cooling therapy) in 52 cases and cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) in 45 cases. The rate of complete response (CR), defined as complete resolution of disease activity, was 17% for cooling therapy and 13% for CHOP. Virological CR was not observed. The 3-year overall survival rates in patients treated with chemotherapy only (n = 20), chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT; n = 47), and allo-HSCT only (n = 12) were 0%, 65%, and 82%, respectively. Distinct characteristics were observed between childhood- and elderly-onset sCAEBV, and they appeared to be different disorders. Chemotherapy is currently insufficient to resolve disease activity and eradicate infected cells. The development of an effective treatment is urgently needed.

Chronic Active Epstein–Barr Virus Infection: The Elucidation of the Pathophysiology and the Development of Therapeutic Methods

“…Based on our nationwide survey, the main symptoms and signs of sCAEBV in diagnosis were: fever (85%), hepatosplenomegaly (70%), lymphadenopathy (53%), cardiac dysfunction (9%), aneurysm (9%), gastrointestinal symptoms (8%), neurological symptoms (8%), vasculitis (7%), uveitis (4%), and HLH (26%). The main laboratory findings were neutropenia (16%), anemia (14%), thrombocytopenia (30%), high ALT (31%), and high sIL-2R (27%) [ 4 ]. Because sCAEBV shows various clinical features, patients may first visit any department in hospitals.…”

“…The WHO 2017 classification specifies that HV-LPD and sMBA are the conditions of which the lesions are limited to the skin [ 3 ]. Although the WHO 2017 classification mentions the proliferation of only EBV-infected NK-cells in the lesioned area of sMBA, there are also cases of infected T-cells [ 4 , 9 ].…”

“…Therefore, biopsy is usually challenging. According to the Japanese nationwide survey, only 15% of all the cases succeeded in diagnosing CAEBV by histology [ 4 ]. All other cases diagnosed CAEBV by detecting EBV-DNA or EBNA in separated T- or NK-cells from PB.…”

“…The nationwide survey of sCAEBV in Japan by the author and colleagues is the first large-scale study of sCAEBV conducted after the publication of the WHO 2017 classification [ 4 ]. The summary of the survey is as follows.…”

“…Based on the diagnostic criteria coinciding with that of the WHO 2017 classification, the author and colleague researchers conducted a nationwide fact-finding survey in Japan to investigate the clinical features and treatment strategies of CAEBV. The results of this survey were reported and published in 2020 [ 4 ]. The aims of this review are to summarize the results of the survey and to raise issues on the WHO 2017 classification, citing from the survey report.…”