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 NK cells with lymphoproliferation, organ failure due to infiltration of tissues with virus-infected cells, hemophagocytic lymphohistiocytosis (HLH) and/or lymphoma. The disease is more common in Asia than in the United States and Europe. While 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 for the disease varied widely, although most patients ultimately proceeded to HSCT. Though patients undergoing HSCT had better survival than those who did not (55% v 25%, p<0.01), 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% v 35%, p=0.1). 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.

EBV‐positive diffuse large B‐cell lymphoma, not otherwise specified: 2022 update on diagnosis, risk‐stratification, and management

“…CAEBV is a systemic T‐ or NK‐cell lymphoproliferative disorder of immunosuppressed patients and it is defined by the presence of mononucleosis‐like symptoms for more than 3 months, high levels of EBV DNA in peripheral blood, as well as histological and RNA EBV tissue involvement 49,50 . It is a rare disorder, affecting children, and young adults more commonly, and there is no sex predilection.…”

Massive pericardial effusion due to chronic active Epstein–Barr virus infection successfully treated with PD-1 blockade: A case report

“…CAEBV is a rare but life-threatening EBV-positive lymphoproliferative disease characterized by high levels of EBV in the blood and tissues and organ infiltration of EBV-infected T- and NK cells. [1,2,5] Currently, the diagnosis of CAEBV should meet the following criteria: IM-like symptoms persisting for >3 months, increased EBV-DNA in the peripheral blood, demonstration of EBV-RNA or viral proteins in affected tissues, and no evidence of immunodeficiency. [1] Most patients with CAEBV have systemic presentations such as fever, hepatosplenomegaly, lymphadenopathy, cytopenia, and skin rash.…”

“…Prognosis is associated with EBV-DNA viral loads, platelet levels, and age at onset. [5,6] At present, treatment options for patients with CAEBV are limited. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only way to cure CAEBV; however, severe complications due to EBV infection, lack of appropriate donors, and disease relapse after transplantation remain challenging.…”

A young woman with persistent sore throat, Epstein–Barr virus, lymphadenopathy, and aberrant CD4 + CD7‐ T‐cells

“…35 Despite HSCT showing improved survival in several studies, Saldana et al found that 20 of 44 patients who underwent HSCT outside of Asia died at 52 months with most due to relapsed disease. 5,37 In conclusion, CAEBV is an important diagnostic consideration in patients presenting with recurrent or persistent IM-like symptoms.…”