Fever in Children with Cancer: Pathophysiological Insights Using Blood Transcriptomics

Area of Science:

• Pediatric Oncology
• Infectious Diseases
• Molecular Biology

Background:

• Fever is common in children undergoing chemotherapy, often due to infections or inflammation.
• Current diagnostic methods are insufficient, leading to prolonged antibiotic use even with negative blood cultures.
• Understanding the causes of fever is crucial for appropriate treatment in pediatric cancer patients.

Purpose of the Study:

• To investigate the pathophysiological mechanisms of fever in children with hematological malignancies using blood transcriptomics.
• To differentiate between infectious (bacteremia) and non-infectious causes of fever.
• To identify potential biomarkers for guiding antibiotic therapy.

Main Methods:

• A nationwide study involving 168 febrile episodes in children with hematological malignancies.
• Whole blood samples collected in PAXgene tubes for single-cell RNA sequencing.
• Comparison of transcriptomic profiles between febrile children with and without bacteremia.

Main Results:

• Children with bacteremia showed differentially expressed genes related to immunoregulation, cardiac, and vascular function.
• Children without bacteremia exhibited distinct gene expression patterns, suggesting viral or other inflammatory causes.
• Overlapping differentially expressed genes were identified with previously established transcriptomics-based signatures.

Conclusions:

• Blood transcriptomics offers novel insights into fever mechanisms in pediatric cancer patients.
• Distinct gene expression patterns can indicate viral infections or non-bacterial inflammation in children with negative blood cultures.
• These findings support the early discontinuation of antibiotics in febrile children with cancer when infection is not confirmed.