Cytokine Release Syndrome Following CD19 Directed Chimeric Antigen Receptor T-Cell Therapy

Uri Greenbaum, Jeremy L. Ramdial, Aimaz Afrough, Leonard C. Alsfeld, Sassine Ghanem, May Daher, Amanda Olson, Partow Kebriaei, Paolo Strati, Raphael E. Steiner, Sairah Ahmed, Mark R. Tanner, Sattva S. Neelapu, Katayoun Rezvani, Elizabeth J. Shpall

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


Chimeric antigen receptor (CAR) T-cell therapies have emerged as novel and promising treatments for hematologic malignancies. However, this new technology is associated with unique complications. Cytokine release syndrome (CRS) is a potentially severe side effect that can arise following infusion of CAR T-cells that consists of a systemic increase in proinflammatory cytokines, leading to serious toxicities. In this chapter, we discuss the rates of CRS that have been reported in clinical trials and real-world data, along with the predictive factors and biomarkers of CRS. We provide an overview of the pathogenesis of CRS, including the cytokines and cell-types that are drivers of this complication. We also discuss the diagnosis, grading, and management of CRS. Finally, we review secondary hemophagocytic lymphohistiocytosis and macrophage activation syndrome, a rare and serious adverse event following CAR T-cell therapy that is related, yet distinct from CRS. Overall, while the advent of CAR T-cell therapies as standard of care has initiated a paradigm shift in our treatment of hematologic diseases, understanding the underlying pathogenesis, diagnosis, and management of CRS will be critical for the continued and expanding use of these novel therapies.

Original languageEnglish
Title of host publicationManual of Hematopoietic Cell Transplantation and Cellular Therapies
Number of pages16
ISBN (Electronic)9780323798334
ISBN (Print)9780323798341
StatePublished - 1 Jan 2023
Externally publishedYes


  • CAR
  • CRS
  • chimeric antigen receptor
  • cytokine release syndrome
  • toxicities

ASJC Scopus subject areas

  • General Medicine


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