Clinical features and prognostic factors of adult systemic chronic active <scp>EBV</scp> disease: A retrospective analysis in Japan

Systemic chronic active Epstein-Barr virus disease (sCAEBV) is a life-threatening disorder characterized by Epstein-Barr virus (EBV) infection in T cells and/or natural killer (NK) cells leading to systemic inflammation. We retrospectively analysed 46 adult patients diagnosed with sCAEBV at two high-volume centres in Japan. Patients with active disease received immunosuppressive therapy, chemotherapy-based regimens and/or ruxolitinib. Allogeneic haematopoietic stem cell transplantation (allo-HSCT) was pursued whenever feasible. Of 46 patients, 41 (89.1%) ultimately underwent allo-HSCT. Five patients progressed from hydroa vacciniforme lymphoproliferative disorder (HV-LPD); all showed EBV-infected CD4+ cells. The 3-year overall survival (OS) was 43.1% (95% confidence interval [CI], 27.7-57.5), and all patients who did not undergo allo-HSCT died within 8 months from diagnosis. Five patients (10.9%) developed lymphoma or leukaemia. Leading causes of death included haemophagocytic lymphohistiocytosis and infections. Multivariable analysis identified high alanine aminotransferase (ALT) and ferritin as independent predictors of poor outcome. Based on these findings, we developed a risk model stratifying patients into three groups with distinct 3-year OS rates: 69.9% (95% CI, 44.6-85.3) in patients with neither factor, 24.8% (95% CI, 7.0-48.2) in those with one factor and 0% in those with both factors (p < 0.001). ALT and ferritin are practical biomarkers for risk stratification and treatment.