IEC-HS (immune effector cell-associated HLH-like syndrome)

An American Society for Transplantation and Cellular Therapy panel (Hines et al., 2023) proposed the term to describe haemophagocytic lymphohistiocytosis (HLH)-like toxicities seen across CAR-T products and patient groups, often not tied to the severity of cytokine release syndrome. It defines IEC-HS as a pathological, biochemical hyperinflammatory syndrome that manifests with features of macrophage activation/HLH, is attributable to immune effector cell therapy, and is associated with progression or new onset of cytopenias, hyperferritinaemia, coagulopathy with hypofibrinogenaemia and/or transaminitis. It is often delayed, manifesting as CRS resolves, and the term should not be used for manifestations of severe CRS alone. Hyperferritinaemia (more than twice the upper limit of normal or baseline, and/or rising rapidly) is a prerequisite for the more specific criteria, and the panel proposes a grading schema and treatment approaches: anakinra with corticosteroids as first-line agents, ruxolitinib where more is needed, and emapalumab as a possible agent whose use in adults is extrapolative.