Diagnostic biomarkers to differentiate sepsis from cytokine release syndrome in critically ill children
Open accessAbstract
Chimeric antigen receptor (CAR) T-cells directed against CD19 have drastically altered outcomes for children with relapsed and refractory acute lymphoblastic leukemia (r/r ALL). Pediatric patients with r/r ALL treated with CAR-T are at increased risk of both cytokine release syndrome (CRS) and sepsis. We sought to investigate the biologic differences between CRS and sepsis and to develop predictive models which could accurately differentiate CRS from sepsis at the time of critical illness. We identified 23 different cytokines that were significantly different between patients with sepsis and CRS. Using elastic net prediction modeling and tree classification, we identified cytokines that were able to classify subjects as having CRS or sepsis accurately. A markedly elevated interferon γ (IFNγ) or a mildly elevated IFNγ in combination with a low IL1β were associated with CRS. A normal to mildly elevated IFNγ in combination with an elevated IL1β was associated with sepsis. This combination of IFNγ and IL1β was able to categorize subjects as having CRS or sepsis with 97% accuracy. As CAR-T therapies become more common, these data provide important novel information to better manage potential associated toxicities.
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Levels of serum cytokines - most prominently interferon-γ - are often more elevated in patients with cytokine storm due to CAR T-cell therapy than in patients with sepsis-induced cytokine storm.
“Levels of serum cytokines — most prominently, interferon-γ — are often more elevated in patients with cytokine storm due to CAR T-cell therapy than in patients with sepsis-induced cytokine storm”
From Cytokine storm (2020) · cites this paper as [12]
Patients with sepsis-induced cytokine storm often have higher levels of circulating interleukin-1β, procalcitonin, and markers of endothelial damage than patients with CAR T-cell therapy-induced cytokine storm.
“who often have higher levels of circulating interleukin-1β, procalcitonin, and markers of endothelial damage”
From Cytokine storm (2020) · cites this paper as [12]
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References 36 · Cited by 61
- Authors
- Diorio, C., Shaw, P. A., Pequignot, E., Orlenko, A., Chen, F., Aplenc, R., Barrett, D. M., Bassiri, H., Behrens, E., DiNofia, A. M., Gonzalez, V., Koterba, N., Levine, B. L., Maude, S. L., Meyer, N. J., Moore, J. H., Paessler, M., Porter, D. L., Bush, J. L., Siegel, D. L., Davis, M. M., Zhang, D., June, C. H., Grupp, S. A., Melenhorst, J. J., Lacey, S. F., Weiss, S. L., & Teachey, D. T.
- Affiliations
- Children's Hospital of Philadelphia (US)
- Department of Biostatistics, Epidemiology, and Informatics,
- Center for Cellular Immunotherapies,
- Abramson Cancer Center (US)
- Division of Infectious Diseases and
- Division of Pulmonary and Critical Care Medicine, and
- University of Pennsylvania (US)
- Division of Critical Care Medicine and
- Corresponding author
- Diorio, Caroline
- Shaw, Pamela A.
- Melenhorst, J. Joseph
- Lacey, Simon F.
- Weiss, Scott L.
- Teachey, David T.
- ORCID
- Diorio, Caroline
- Shaw, Pamela A.
- Orlenko, Alena
- Chen, Fang
- Aplenc, Richard
- Barrett, David M.
- Bassiri, Hamid
- Behrens, Edward
- DiNofia, Amanda M.
- Gonzalez, Vanessa
- Koterba, Natalka
- Levine, Bruce L.
- Maude, Shannon L.
- Meyer, Nuala J.
- Moore, Jason H.
- Porter, David L.
- Siegel, Don L.
- Davis, Megan M.
- Zhang, Donglan
- June, Carl H.
- Grupp, Stephan A.
- Melenhorst, J. Joseph
- Lacey, Simon F.
- Weiss, Scott L.
- Teachey, David T.
- Venue
- Blood Advances
- Publisher
- American Society of Hematology
- Published
- 2020-10-23
- Volume
- 4
- Issue
- 20
- Pages
- 5174-5183
- ISSN
- 2473-9529 (ISSN-L)
- 2473-9537
- PMC
- PMC7594400
- OpenAlex
- W3094121937
- Cited by
- 61
- References
- 36
- Citations by year
- 2026: 5 · 2025: 16 · 2024: 10 · 2023: 9 · 2022: 9 · 2021: 11 · 2020: 1
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Blood Advances (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA193776, P01CA214278)
- National Institute of General Medical Sciences (K23GM110496)
- National Institute of Allergy and Infectious Diseases (R01AI116794)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD047349)
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Keywords
- cytokine release syndrome, sepsis, CAR T-cell therapy, interferon-gamma, IL-1β, cytokine biomarkers, differential diagnosis, critically ill children, CAR-T toxicity
- MeSH terms
- Cytokine Release Syndrome, Child, Humans, Receptors, Antigen, T-Cell, Critical Illness, Sepsis, Precursor Cell Lymphoblastic Leukemia-Lymphoma
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