High risk of relapsed disease in patients with NK/T-cell chronic active Epstein-Barr virus disease outside of Asia

Abstract

Chronic active Epstein-Barr virus (EBV) disease (CAEBV) is characterized by high levels of EBV predominantly in T and/or natural killer cells with lymphoproliferation, organ failure due to infiltration of tissues with virus-infected cells, hemophagocytic lymphohistiocytosis, and/or lymphoma. The disease is more common in Asia than in the United States and Europe. Although allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only curative therapy for CAEBV, its efficacy and the best treatment modality to reduce disease severity prior to HSCT is unknown. Here, we retrospectively assessed an international cohort of 57 patients outside of Asia. Treatment of the disease varied widely, although most patients ultimately proceeded to HSCT. Though patients undergoing HSCT had better survival than those who did not (55% vs 25%, P < .01), there was still a high rate of death in both groups. Mortality was largely not affected by age, ethnicity, cell-type involvement, or disease complications, but development of lymphoma showed a trend with increased mortality (56% vs 35%, P = .1). The overwhelming majority (75%) of patients who died after HSCT succumbed to relapsed disease. CAEBV remains challenging to treat when advanced disease is present. Outcomes would likely improve with better disease control strategies, earlier referral for HSCT, and close follow-up after HSCT including aggressive management of rising EBV DNA levels in the blood.

Graphical abstract

Figure 1.

Disease manifestations in patients with CAEBV. The number of patients is shown in the bars, and the percentage is on the y-axis.

Figure 2.

Treatments received in patients with CAEBV before HSCT. Treatment approaches varied; the most common approaches included chemotherapy and combination bortezomib/ganciclovir.

Figure 3.

Kaplan-Meier plot of survival in patients undergoing HSCT (blue line) or no HSCT (red line). Median survival time was 52 months in the HSCT group and 12.5 months in the no-HSCT group. The number of patients still evaluable at different times after HSCT is shown below the graph.