Introduction to a review series on hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of life-threatening hyperinflammation that challenges pediatric and adult hematologists. Deputy Editors Helen E. Heslop and Jorge Di Paola introduce a 2-piece review series on this rare condition that, once seen, is not forgotten. Its descriptive name reflects an era when we did not understand the pathobiology of a group of diseases unified in common presenting features reflecting uncontrolled immune activation and excessive proinflammatory cytokine production. Verkamp, Jordan, and Allen address pediatric HLH, which is now well recognized to be underpinned by genetic lesions that undermine immune-cell cytotoxicity. They describe how presentations are driven by the intersection of genetic susceptibility and environmental triggers. Hsu, Nikiforow, and Berliner review adult-onset HLH, which is more heterogeneous with a wide array of provoking stimuli and which often occurs in the absence of a known predisposing genetic immune defect. Both reviews cover recent advances arising from the use of targeted therapies directed at activated T cells and cytokine signaling pathways. The role of allogeneic stem cell transplantation is emphasized for pediatric patients, and the recently described entity “immune effector cell–associated HLH-like syndrome” after chimeric antigen receptor T-cell therapy is also explained.