Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor–modified T-cell therapy
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Key Points: Characterization of the kinetics and risk factors for severe CRS after CD19 CAR T cells will facilitate preemptive therapy and management. Severe CRS is characterized by endothelial activation.
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Therapy for cytokine release syndrome and its neurological toxicity chiefly targets IL-6, which probably originates from monocytes or activated endothelial cells.
“Treatment for CRS and associated neurotoxicity primarily targets IL-6, likely arising from monocytes or activated endothelium [1, 6, 11–17].”
From Immune reconstitution and clinical recovery following anti-CD28 antibody (TGN1412)-induced cytokine storm (2021) · cites this paper as [17]
The incidence and kinetics of CRS and neurotoxicity section reports treating patients with tocilizumab and/or dexamethasone, and the Discussion describes these as widely used approaches for severe CRS. The Discussion also reports elevated IL-6 in severe CRS, but it does not identify monocytes or activated endothelium as its source; instead, it discusses IL-6 as a possible contributor to endothelial activation. Page numbers were not available in our copy. (LLM, conf=0.83)
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- Authors
- Hay, K. A., Hanafi, L.-A., Li, D., Gust, J., Liles, W. C., Wurfel, M. M., López, J. A., Chen, J., Chung, D., Harju-Baker, S., Cherian, S., Chen, X., Riddell, S. R., Maloney, D. G., & Turtle, C. J.
- Affiliations
- University of British Columbia (CA)
- Fred Hutch Cancer Center (US)
- Juno Therapeutics (United States) (US)
- Seattle Children's Hospital (US)
- University of Washington (US)
- Bloodworks Northwest (US)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2017-11-23
- Volume
- 130
- Issue
- 21
- Pages
- 2295-2306
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC5701525
- OpenAlex
- W2756071038
- Cited by
- 1,156
- References
- 33
- Citations by year
- 2026: 113 · 2025: 110 · 2024: 124 · 2023: 140 · 2022: 136 · 2021: 167 · 2020: 180 · 2019: 108 · 2018: 68 · 2017: 6 · 2012: 2
- FWCI
- 43.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (CA15704, DK56465)
- Juno Therapeutics
- National Heart, Lung, and Blood Institute (R01HL137991)
- National Cancer Institute (P30CA 15704, CA136551, R01CA136551, CA 15704+, P30CA015704)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30-DK56465, DK 56465, P30DK056465, P30 CA15704, CA15704)
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- cytokine release syndrome, central memory T cells, angiopoietin-2, von Willebrand factor, endothelial activation, biomarkers, early intervention, lymphocyte depletion, capillary leak syndrome, disseminated intravascular coagulation
- MeSH terms
- Adult, Aged, Blood Coagulation Disorders, Female, Fever, Hematopoiesis, Hemodynamics, Humans, Kinetics, Male, Middle Aged, Receptors, Antigen, T-Cell, Risk Factors, Syndrome, T-Lymphocytes, Biomarkers, Tumor, Multivariate Analysis, Cytokines, Immunotherapy, Adoptive, Treatment Outcome, Lymphocyte Count, Neurotoxicity Syndromes, Endothelial Cells, Young Adult
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