The clinical significance and prognostic role of whole-blood Epstein-Barr virus DNA in lymphoma-associated hemophagocytic lymphohistiocytosis

Abstract

Abstract Purpose: To evaluate the role of circulating Epstein-Barr virus (EBV) DNA in lymphoma-associated hemophagocytic lymphohistiocytosis. Methods: We retrospectively analyzed 306 adult patients with lymphoma-associated hemophagocytic lymphohistiocytosis admitted to the First Affiliated Hospital of Nanjing Medical University from August 2009 to November 2022. Results: T/NK-cell malignancies (54.3%, 166/306) were the most common subtypes, followed by B-cell non-Hodgkin lymphoma (38.2%, 117/306). Elevated whole-blood EBV DNA was observed in 55.8% (164/294) of the patients and the median number was significantly higher in the T/NK malignancies (199500, 30000-1390000) than that in the B-cell non-Hodgkin lymphoma (5520, 1240-28400, P < 0.001). The optimum cutoff value for the overall survival of EBV DNA was determined as 43600 copies/mL. Compared to the patients with EBV DNA ≤ 43600 copies/mL, those with EBV DNA > 43600 copies/mL were younger and had more T/NK-cell malignancies, more bone marrow infiltration, lower levels of neutrophils and fibrinogen, and higher levels of alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase, triacylglycerol, and β2-microglobulin. A higher load of EBV DNA (> 43600 copies/mL), thrombocytopenia (< 100×109/L), neutropenia (< 1×109/L), hypofibrinogenemia (≤ 1.5 g/L), and elevated levels of creatinine (> 133 μmol/L) were independent adverse predictors of overall survival. A prognostic index based on EBV DNA and the other four factors was established to categorize the patients into four groups with significantly different outcomes. Conclusion: Our study identified high EBV load as a risk factor for lymphoma-associated HLH and established a prognostic index based on EBV DNA to predict patients’ outcomes.