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Intestinal mucositis flags bloodstream infections in feverish children with leukaemia

Author:  Lynda Williams

medwireNews: Monitoring biomarkers of intestinal mucositis in children undergoing treatment for acute leukaemia who develop fever may identify those at risk for bloodstream infections (BSIs), Danish researchers have found.

The team reports in Leukemia that the likelihood of BSI among 85 children with new-onset fever was significantly predicted by changes in levels of the enterocyte loss biomarker citrulline, the intestinal antimicrobial peptide regenerating islet-deprived-protein (REG)3α and three different chemokines.

“Controlled, clinical trials are needed to investigate whether these markers can be used clinically to guide antimicrobial therapy”, say Sarah Weischendorff (Rigshospitalet, Copenhagen) and co-authors.

The study included children with a temperature of 38.5  ̊C or higher on one measurement or who had a temperature of at least 38.0  ̊C for more than 1 hour while receiving treatment for acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML). The patients experienced a median of two febrile episodes each, 69% had at least two episodes and 63 children were diagnosed with neutropenia.

Overall, bacterial or fungal BSIs were confirmed by positive blood culture in 14% of the 242 febrile episodes reported and BSIs were more common among children with neutropenia (20% of 122 febrile episodes) than in those without (9% of 120 febrile episodes). Thus, children with neutropenia were a significant 2.35 times more likely to develop BSIs than those with an adequate number of neutrophils.

By contrast, Weischendorff et al found no association between the likelihood of BSIs and patient sex or age, although there was a trend towards more BSIs among children with AML or biphenotypical acute leukaemia than those with ALL (50 vs 23%).

Moreover, patients with BSIs had significantly lower levels of citrulline than those without BSIs, as well as significantly higher levels of the mucosal immune regulatory chemokine CCL20, especially among children with febrile neutropenia. BSIs were also associated with a significant increase in levels of REG3α and the two neutrophil chemoattracts CXCL1 and CXCL8.

After considering sex, age, neutropenia and diagnosis, changes in all these biomarkers were associated with a significant increase in the likelihood of BSIs, with odds ratios ranging from 1.5 to 1.8.

Using receiver operating characteristic curve analysis, the researchers found that sensitivity for detection of BSIs among patients with febrile neutropenia was significantly improved when considering levels of citrulline (91%), CCL20 (91%), CXCL8(91%), REG3α (96%) or CXCL1 (96%) alongside the current diagnostic biomarkers of procalcitonin and C-reactive protein, versus use of these standard measures alone (71 and 57%, respectively).

The researchers acknowledge the low specificities for use of the mucositis biomarkers, ranging from 27% to 31%, but remark that “[e]ven with this limitation, the ability to exclude severe infections in 25% of all febrile neutropenic episodes has the potential to enhance safety when considering early antibiotic cessation.”

Weischendorff and co-workers conclude: “Our results further indicate that a dysregulated intestinal barrier is a significant risk factor for invasive infections and that monitoring intestinal mucositis by quantitative markers may serve as a potential diagnostic approach to detect BSI-related fever episodes.

“These findings also emphasize the importance of protecting the gastrointestinal barrier during chemotherapy to reduce infectious morbidity, which merits increased clinical and scientific priority.”

News stories are provided by medwireNews, which is an independent medical news service provided by Springer Healthcare Ltd. © 2023 Springer Healthcare Ltd, part of the Springer Nature Group  

This independent news story was supported by an educational grant from L’Institut Servier, Suresnes, France.

Leukemia 2023; doi:10.1038/s41375-023-02077-7

Image Credits: © Suzi Media /

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Lynda Williams

medwireNews Deputy Bureau Chief