Successful Treatment of Adult Epstein–Barr Virus‐Associated Hemophagocytic Lymphohistiocytosis With Etoposide Guided by Plasma Epstein–Barr Virus DNA Monitoring: A Case Report

Hemophagocytic lymphohistiocytosis (HLH) is a life‐threatening hyperinflammatory syndrome. Epstein–Barr virus (EBV)‐associated HLH is a major subtype of secondary HLH, requiring prompt diagnosis and treatment. However, treatment is particularly challenging in patients with severe coagulopathy and hepatic dysfunction. A previously healthy 23‐year‐old woman presented with a 2‐week history of high‐grade fever and cervical lymphadenopathy. Cytopenia, elevated lactate dehydrogenase levels, marked transaminase elevations, hyperferritinemia, and disseminated intravascular coagulation were observed. EBV‐associated HLH was diagnosed based on bone marrow hemophagocytosis, an elevated whole blood EBV‐DNA level (6.63 log IU/mL), and serological findings consistent with primary EBV infection. Initial treatment with methylprednisolone and cyclosporine A was followed by weekly oral etoposide, with careful monitoring in the setting of severe hepatic dysfunction. Clinical symptoms and laboratory abnormalities improved within 3 weeks of starting etoposide. Plasma EBV‐DNA became undetectable during treatment, and oral etoposide was discontinued after the third weekly course on Day 18, with a total cumulative dose of 750 mg, corresponding to approximately 450 mg/m 2 . The patient showed no evidence of relapse at the 6‐month follow‐up, with sustained negativity of plasma EBV‐DNA. This case suggests that timely etoposide‐based therapy may be feasible in severe EBV‐HLH when response and toxicity are carefully monitored. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission.