Diagnostic biomarkers to differentiate sepsis from cytokine release syndrome in critically ill children
| Autor: | Simon F. Lacey, Caroline Diorio, Edward M. Behrens, David M. Barrett, David L. Porter, Fang Chen, Jenny Bush, Bruce L. Levine, Alena Orlenko, Edward Pequignot, J. Joseph Melenhorst, Jason H. Moore, Natalka Koterba, Pamela A. Shaw, Richard Aplenc, Donglan Zhang, Michele Paessler, David T. Teachey, Vanessa E. Gonzalez, Don L. Siegel, Hamid Bassiri, Stephan A. Grupp, Megan M. Davis, Nuala J. Meyer, Scott L. Weiss, Amanda M. DiNofia, Shannon L. Maude, Carl H. June |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Immunobiology and Immunotherapy Critical Illness T cell Receptors Antigen T-Cell CD19 Sepsis 03 medical and health sciences 0302 clinical medicine Antigen Refractory otorhinolaryngologic diseases medicine Humans Child Receptor biology business.industry Hematology Precursor Cell Lymphoblastic Leukemia-Lymphoma medicine.disease Chimeric antigen receptor Cytokine release syndrome 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Immunology biology.protein Cytokine Release Syndrome business |
| Zdroj: | Blood Adv |
| ISSN: | 2473-9537 2473-9529 |
| DOI: | 10.1182/bloodadvances.2020002592 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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