A distinct subtype of Epstein-Barr virus-positive T/NK-cell lymphoproliferative disorder: adult patients with chronic active Epstein-Barr virus infection-like features

Abstract

The characteristics of adult patients with chronic active Epstein-Barr virus infection are poorly recognized, hindering early diagnosis and an improved prognosis. We studied 54 patients with adult-onset chronic active Epstein-Barr virus infection diagnosed between 2005 and 2015. Adult onset was defined as an estimated age of onset of 15 years or older. To characterize the clinical features of these adults, we compared them to those of 75 pediatric cases (estimated age of onset <15 years). We compared the prognosis of adult-onset chronic active Epstein-Barr virus infection with that of patients with nasal-type (n=37) and non-nasal-type (n=45) extranodal NK/T-cell lymphoma. The median estimated age of onset of these lymphomas was 39 years (range, 16-86 years). Compared to patients with pediatric-onset disease, those in whom the chronic active Epstein-Barr virus infection developed in adulthood had a significantly decreased incidence of fever (P=0.005), but greater frequency of skin lesions (P<0.001). Moreover, hypersensitivity to mosquito bites and the occurrence of hydroa vacciniforme were less frequent in patients with adult-onset disease (P<0.001 and P=0.0238, respectively). Thrombocytopenia, high Epstein-Barr virus nuclear antigen antibody titer, and the presence of hemophagocytic syndrome were associated with a poor prognosis (P=0.0087, P=0.0236, and P=0.0149, respectively). Allogeneic hematopoietic stem cell transplantation may improve survival (P=0.0289). Compared to pediatric-onset chronic active Epstein-Barr virus infection and extranodal NK/T-cell lymphoma, adult-onset chronic active Epstein-Barr virus infection had a poorer prognosis (P<0.001 and P=0.0484, respectively). Chronic active Epstein-Barr virus infection can develop in a wide age range, with clinical differences between adult-onset and pediatric-onset disease. Adult-onset chronic active Epstein-Barr virus infection is a disease with a poor prognosis. Further research will be needed.

Figure 1.

Approximate time from estimated onset and survival. The figure shows the periods from estimated onset to diagnosis of chronic active Epstein-Barr virus infection/discontinuation of observation. In most cases more than one year elapsed from the estimated onset to the diagnosis.

Figure 2.

Indicators for predicting prognosis in terms of overall survival in adult-onset chronic active Epstein-Barr virus (EBV) infection patients. Although infected-cell type (A) and histological classification (B) were not prognostic factors for overall survival (P=0.587 and P=0.822, respectively), thrombocytopenia (B), platelet count < 100×10⁹/L), EBNA antibody titer ≥ 40 (C), the presence of hemophagocytosis syndrome (HPS) (D) at the initial diagnosis were poor prognostic indicators for overall survival (P=0.0087, P=0.0236, and P=0.0149, respectively). With regards to treatment, allogeneic HSCT improved survival (F) (P=0.0289). CAEBV: chronic active EBV infection; EBNA: Epstein–Barr virus nuclear antigen 1; EBV: Epstein-Barr virus; HPS: hemophagocytic syndrome; HSCT: hematopoietic stem cell transplantation.

Figure 3.

Comparison of overall survival. Adult-onset chronic active Epstein-Barr virus infection may be a distinct entity with a poorer prognosis compared to pediatric-onset CAEBV and extranodal NK/T-cell lymphoma, nasal type (P<0.001 and P=0.0484, respectively).

Figure 4.

Comparison of survival for overall survival. When extranodal NK/T-cell lymphoma, nasal type (ENKTL) was divided into “nasal type” and “non-nasal type” according to the anatomical sites of development, there was no statistical difference in prognosis between non-nasal type ENKTL and adult-onset chronic active Epstein-Barr virus infection (P=0.922).