TY - JOUR
T1 - Fever in Children with Cancer
T2 - Pathophysiological Insights Using Blood Transcriptomics
AU - Smedegaard, Lotte Møller
AU - Dungu, Kia Hee Schultz
AU - Guo, Yuliu
AU - Hjalgrim, Lisa Lyngsie
AU - Probst, Victoria
AU - Mariani, Luca
AU - Grosen, Dorthe
AU - Kristensen, Ines
AU - Tuckuviene, Ruta
AU - Schmiegelow, Kjeld
AU - Bagger, Frederik Otzen
AU - Vissing, Nadja Hawwa
AU - Nygaard, Ulrikka
N1 - Publisher Copyright:
© 2025 by the authors.
PY - 2025/8
Y1 - 2025/8
N2 - Fever is a frequent complication in children receiving chemotherapy, primarily caused by bloodstream infections and non-infectious inflammation. Yet, the pathophysiological mechanisms remain unclear, and diagnostics are insufficient, which often results in continued antibiotic treatment despite negative blood cultures. In a nationwide study, we collected whole blood in PAXgene tubes from 168 febrile episodes in children with hematological malignancies, including 37 episodes with bacteremia, and performed single-cell RNA sequencing. We compared transcriptomic profiles between febrile children with and without bacteremia. In children with bacteremia, differentially expressed genes were related to immunoregulation and cardiac and vascular function. Children without bacteremia had distinct gene expression patterns, suggesting a viral or other inflammatory cause of fever. Several differentially expressed genes overlapped with previously published transcriptomics-based diagnostic signatures developed in immunocompetent children. In conclusion, blood transcriptomics provided novel insights into the pathophysiological mechanisms of febrile children with hematological malignancies. We found differentially expressed genes suggesting viral infections or non-bacterial inflammation as causes of fever in children with negative blood cultures, supporting early antibiotic discontinuation in children with cancer.
AB - Fever is a frequent complication in children receiving chemotherapy, primarily caused by bloodstream infections and non-infectious inflammation. Yet, the pathophysiological mechanisms remain unclear, and diagnostics are insufficient, which often results in continued antibiotic treatment despite negative blood cultures. In a nationwide study, we collected whole blood in PAXgene tubes from 168 febrile episodes in children with hematological malignancies, including 37 episodes with bacteremia, and performed single-cell RNA sequencing. We compared transcriptomic profiles between febrile children with and without bacteremia. In children with bacteremia, differentially expressed genes were related to immunoregulation and cardiac and vascular function. Children without bacteremia had distinct gene expression patterns, suggesting a viral or other inflammatory cause of fever. Several differentially expressed genes overlapped with previously published transcriptomics-based diagnostic signatures developed in immunocompetent children. In conclusion, blood transcriptomics provided novel insights into the pathophysiological mechanisms of febrile children with hematological malignancies. We found differentially expressed genes suggesting viral infections or non-bacterial inflammation as causes of fever in children with negative blood cultures, supporting early antibiotic discontinuation in children with cancer.
KW - bloodstream infection
KW - differential gene expression
KW - febrile neutropenia
KW - pediatric oncology
KW - transcriptomics
UR - https://www.scopus.com/pages/publications/105013303099
U2 - 10.3390/ijms26157126
DO - 10.3390/ijms26157126
M3 - Journal article
C2 - 40806258
AN - SCOPUS:105013303099
SN - 1661-6596
VL - 26
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 15
M1 - 7126
ER -