Introduction: Besides cytokine release syndromes (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), immune effector cell-associated HLH-like syndrome (IEC-HS) is increasingly recognized across CAR-T recipients. This emergent and fatal syndrome is difficult to separate from other disorders during the early phase, and urgently requires more integrated diagnostic and therapeutic frameworks.
Areas covered: Existing literature has pointed out the potential role of unbridled proliferation of cytotoxic T lymphocytes, lymphopenia of natural killing cells, and hypercytokinemia in triggering the IEC-HS. The onset time of IEC-HS usually overlaps with CRS or be delayed from CRS. Clinical features include hyperferritinemia, hepatic and renal dysfunctions, cytopenias, coagulopathy, and hemophagocytosis. Multiple diagnostic criteria are based predominantly on ferritin elevation and prerequisite CRS. Corticosteroids are the cornerstone for IEC-HS treatment, while cytokine-targeted agents and pathway inhibitors offer great promise in alleviating IEC-HS syndromes.
Expert opinions: Several controversial predisposing factors of IEC-HS like disease burden should be further investigated. Futures research is anticipated to identify the real-time biomarkers, as well as develop a more sophisticated grading and management network.
Keywords: Chimeric antigen receptor T cell therapy; cytokine release syndrome; hemophagocytic lymphohistiocytosis; immune effector cell-associated hlh-like syndrome; immune effector cell-associated neurotoxicity syndrome.