Childhood cancers

Predicting benign and severe febrile neutropenia in paediatric cancer using gene signatures

Australian researchers say they have figured out how to identify which child cancer patients are at greatest risk of developing serious infection during febrile neutropenia (FN), potentially paving the way to a diagnostic test.

Based on genetic sequencing, the discovery could one day mean an end to the need for every patient presenting to hospital with FN to receive prophylactic antibiotics, say the multi-centre team.

The scientists conducted whole-genome transcription profiling on the peripheral blood mononuclear cells in 473 children with cancer and FN, using data from the Australian Predicating Infectious ComplicatioNs In Children with Cancer (PICNICC) study. Some 45% had solid tumours and 55% had a haematological malignancy.

Samples were taken at the time of admission and again on day two, enabling the researchers to compare differences in gene expression associated with the different immune responses in children with and without infection.

These identified 24 distinct gene signatures specific for bacteraemia – three up-regulated and 21 down-regulated – they reported in Clinical & Translational Immunology.

“Interestingly, this signature is dampened after the institution of appropriate antibiotics and is replaced with different signatures indicating a degree of immune recovery,” the authors said.

“We postulate that transcriptomic analysis can potentially identify the cause of fever in neutropenic children with cancer and sequential analyses may provide evidence that the correct treatment has been initiated.”

Differences in gene signatures between episodes with bacteraemia and episodes with bacterial infection, viral infection and clinically defined infection were also observed, they added.

Study co-author Professor Marc Pellegrini from the Walter and Eliza Hall Institute said the findings could prove crucial in developing an early diagnostic test.

“Our landmark data shows that only patients with these specific immune signatures should be treated as FN medical emergencies,” Professor Pellegrini said.

“This project was established to find potential biomarkers that could be tested for, as soon as children with cancer and FN present in hospital. This would enable clinicians to determine a patient’s infection severity and most importantly, to customise treatment.”

“Our findings are a crucial step towards developing this important tool that could spare thousands of children around the world from unnecessary treatment.”

He added the key differences in the immune profiles of benign FN episodes and cases with severe infections were identified as cell death processes of immune cells, specific inflammatory responses and metabolic processes.

Nevertheless, only subtle differences in gene expression profiles between non-bloodstream bacterial and viral infections were identified.

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