Blood transcriptomics identifies immune signatures indicative of infectious complications in childhood cancer patients with febrile neutropenia

Gabrielle M Haeusler, Alexandra L Garnham, Connie Sn Li-Wai-Suen, Julia E Clark, Franz E Babl, Zoe Allaway, Monica A Slavin, Francoise Mechinaud, Gordon K Smyth, Bob Phillips, Karin A Thursky, Marc Pellegrini, Marcel Doerflinger

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Febrile neutropenia (FN) is a major cause of treatment disruption and unplanned hospitalization in childhood cancer patients. This study investigated the transcriptome of peripheral blood mononuclear cells (PBMCs) in children with cancer and FN to identify potential predictors of serious infection.

Methods: Whole-genome transcriptional profiling was conducted on PBMCs collected during episodes of FN in children with cancer at presentation to the hospital (Day 1; n  = 73) and within 8-24 h (Day 2; n  = 28) after admission. Differentially expressed genes as well as gene pathways that correlated with clinical outcomes were defined for different infectious outcomes.

Results: Global differences in gene expression associated with specific immune responses in children with FN and documented infection, compared to episodes without documented infection, were identified at admission. These differences resolved over the subsequent 8-24 h. Distinct gene signatures specific for bacteraemia were identified both at admission and on Day 2. Differences in gene signatures between episodes with bacteraemia and episodes with bacterial infection, viral infection and clinically defined infection were also observed. Only subtle differences in gene expression profiles between non-bloodstream bacterial and viral infections were identified.

Conclusion: Blood transcriptome immune profiling analysis during FN episodes may inform monitoring and aid in defining adequate treatment for different infectious aetiologies in children with cancer.

Original languageEnglish
Article numbere1383
Number of pages14
JournalClinical & translational immunology
Volume11
Issue number5
DOIs
Publication statusPublished - 17 May 2022

Bibliographical note

© 2022 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.

Cite this