In this issue of Blood, Liu et al describe the favorable response of adults with relapsed/refractory Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) to treatment with nivolumab, a programmed cell death-1 (PD-1) inhibitor.1 EBV-HLH presents a challenging clinical conundrum because only a minority of patients will achieve long-standing clinical remission with front-line therapy.(2) To further complicate matters, neither clinical nor pathologic-based criteria have been well established to differentiate which patients are likely to fail upfront HLH therapy with etoposide and dexamethasone.(3,4) Patients with relapsed/refractory disease have a dismal chance of survival because of high rates of disease-related mortality.(2,3)
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