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Immune Effector Cell associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS).
Immune Effector Cell associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS). Transplantation and cellular therapy Hines, M. R., Knight, T. E., McNerney, K. O., Leick, M. B., Jain, T., Ahmed, S., Frigault, M. J., Hill, J. A., Jain, M. D., Johnson, W. T., Lin, Y., Mahadeo, K. M., Maron, G. M., Marsh, R. A., Neelapu, S. S., Nikiforow, S., Ombrello, A. K., Shah, N. N., Talleur, A. C., Turicek, D., Vatsayan, A., Wong, S. W., Maus, M. V., Komanduri, K. V., Berliner, N., Henter, J. I., Perales, M. A., Frey, N. V., Teachey, D. T., Frank, M. J., Shah, N. N. 2023Abstract
T cell mediated hyperinflammatory responses such as cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) are now well-established toxicities of chimeric antigen receptor (CAR) T cells. As the field of CAR T cells advances, however, there is increasing recognition that hemophagocytic lymphohistiocytosis (HLH)-like toxicities following CAR T cell infusions are occurring broadly across patient populations and CAR T cell constructs. Importantly, these HLH-like toxicities are often not as directly associated with CRS and/or its severity as initially described. This emergent toxicity, however ill-defined, is associated with life-threatening complications, creating an urgent need for improved identification and optimal management.With the goal to improve patient outcomes and formulate a framework to characterize and study this HLH-like syndrome, we established an American Society for Transplantation and Cellular Therapy (ASTCT) panel comprised of experts in primary and secondary HLH, pediatric and adult HLH, infectious disease, rheumatology and hematology, oncology, and cellular therapy.Through this effort, we provide an overview of the underlying biology of classical primary and secondary HLH, its relationship with similar manifestations following CAR T cell infusions and propose the term "immune effector cell (IEC) associated HLH-like syndrome (IEC-HS)" to describe this emergent toxicity. Further, we delineate a framework for identification of IEC-HS and put forward a grading schema which can be used to assess severity and facilitate cross-trial comparisons. Additionally, given the critical need to optimize outcomes for patients experiencing IEC-HS, we provide insights into potential treatment approaches, strategies to optimize supportive care and delineate alternate etiologies which should be considered in a patient presenting with IEC-HS.By collectively defining IEC-HS as a hyperinflammatory toxicity we can now embark on further study of the pathophysiology underlying this toxicity profile and make strides towards a more comprehensive assessment and treatment approach.
View details for DOI 10.1016/j.jtct.2023.03.006
View details for PubMedID 36906275