Background: HLH results in dysregulation of the immune system activation, characterized by excessive pro-inflammatory production, which are responsible for the main clinical and biological features of HLH syndrome. In sporadic/adult forms of HLH, treatment is challenging due to the negative effects of corticosteroids on potential infectious related HLH, and etoposide, which may mask hematological neoplasm (H)-associated hemophagocytic lymphohistiocytosis (H-HLH). Cytokines involved in HLH syndrome activate the JAK/STAT pathway in immune cells, particularly gamma- interferon through JAK1. Kinase inhibitors blocking JAK activity, particularly Ruxolitinib a JAK1/2 inhibitor, have shown some efficacy in murine genetic models of HLH. However, JAK2 inhibition may be responsible of cytopenia in contrast to JAK1, which may have an effect on Interferon-gamma signaling. HLH-JAK is the first open-label, phase II study evaluating the use of a selective and potent anti-JAK1 inhibitor, itacitinib, alone for non-severe adult HLH (including relapsing or refractory)