Diagnostic biomarkers to differentiate sepsis from cytokine release syndrome in critically ill children.

Autor:	Diorio C; Division of Hematology and Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics., Shaw PA; Department of Biostatistics, Epidemiology, and Informatics., Pequignot E; Center for Cellular Immunotherapies., Orlenko A; Department of Biostatistics, Epidemiology, and Informatics., Chen F; Center for Cellular Immunotherapies.; Abramson Cancer Center, and.; Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA., Aplenc R; Division of Hematology and Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics.; Abramson Cancer Center, and., Barrett DM; Division of Hematology and Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics., Bassiri H; Division of Infectious Diseases and., Behrens E; Department of Pediatrics.; Division of Rheumatology, Children's Hospital of Philadelphia, Philadelphia, PA., DiNofia AM; Division of Hematology and Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics., Gonzalez V; Center for Cellular Immunotherapies.; Abramson Cancer Center, and.; Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA., Koterba N; Center for Cellular Immunotherapies.; Abramson Cancer Center, and.; Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA., Levine BL; Department of Biostatistics, Epidemiology, and Informatics.; Center for Cellular Immunotherapies.; Abramson Cancer Center, and.; Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA., Maude SL; Division of Hematology and Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics., Meyer NJ; Division of Pulmonary and Critical Care Medicine, and., Moore JH; Department of Biostatistics, Epidemiology, and Informatics., Paessler M; Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA., Porter DL; Abramson Cancer Center, and.; Division of Hematology-Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA., Bush JL; Division of Critical Care Medicine and., Siegel DL; Center for Cellular Immunotherapies.; Abramson Cancer Center, and.; Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA., Davis MM; Center for Cellular Immunotherapies., Zhang D; Division of Critical Care Medicine and., June CH; Center for Cellular Immunotherapies.; Abramson Cancer Center, and.; Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA., Grupp SA; Division of Hematology and Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics.; Abramson Cancer Center, and., Melenhorst JJ; Center for Cellular Immunotherapies.; Abramson Cancer Center, and.; Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA., Lacey SF; Center for Cellular Immunotherapies.; Abramson Cancer Center, and.; Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA., Weiss SL; Division of Critical Care Medicine and.; Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.; Center for Mitochondrial and Epigenomic Medicine at the Children's Hospital of Philadelphia, Philadelphia, PA; and.; Pediatric Sepsis Program at the Children's Hospital of Philadelphia, Philadelphia, PA., Teachey DT; Division of Hematology and Oncology, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics.; Abramson Cancer Center, and.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2020 Oct 27; Vol. 4 (20), pp. 5174-5183.
DOI:	10.1182/bloodadvances.2020002592
Abstrakt:	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. (© 2020 by The American Society of Hematology.)
Databáze:	MEDLINE
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