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

TitleDiagnostic biomarkers to differentiate sepsis from cytokine release syndrome in critically ill children.
Publication TypeJournal Article
Year of Publication2020
AuthorsDiorio C, Shaw PA, Pequignot E, Orlenko A, Chen F, Aplenc R, Barrett DM, Bassiri H, Behrens E, DiNofia AM, Gonzalez V, Koterba N, Levine BL, Maude SL, Meyer NJ, Moore JH, Paessler M, Porter DL, Bush JL, Siegel DL, Davis MM, Zhang D, June CH, Grupp SA, J Melenhorst J, Lacey SF, Weiss SL, Teachey DT
JournalBlood Adv
Volume4
Issue20
Pagination5174-5183
Date Published2020 Oct 27
ISSN2473-9537
Abstract

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.

DOI10.1182/bloodadvances.2020002592
Alternate JournalBlood Adv
PubMed ID33095872