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Updated: Jun 20, 2026
Important Endpoints and Proliferative Markers to Assess Small Intestinal Injury and Adaptation using a Mouse Model of Chemotherapy-Induced Mucositis
Published on: May 12, 2019
Citrulline as a marker for chemotherapy induced mucosal barrier injury in pediatric patients
Michel J van Vliet1, Wim J E Tissing, Edmond H H M Rings
1Division of Pediatric Oncology/Hematology, Beatrix Children's Hospital, University of Groningen, Groningen, The Netherlands.
Insights
The National Cancer Institute criteria for mucosal barrier injury (MBI) are inadequate for children. Plasma citrulline shows promise as a measurable indicator of MBI in pediatric cancer patients.
Area of Science:
- Pediatric Oncology
- Gastroenterology
- Biomarker Discovery
Background:
- Current National Cancer Institute (NCI) criteria for mucosal barrier injury (MBI) are insufficient for pediatric cancer patients.
- There is a need for objective, easily measurable indicators of MBI in this population.
Purpose of the Study:
- To investigate various clinical and laboratory tests for MBI in children with acute myeloid leukemia.
- To identify reliable indicators of MBI severity, inflammation, enterocytic loss, and intestinal permeability.
Main Methods:
- Assessed MBI using NCI criteria and daily gut score (DGS).
- Measured inflammation via plasma and fecal interleukin-8 (IL-8) and fecal calprotectin.
- Evaluated enterocytic loss using plasma citrulline and fecal human DNA/total DNA ratio.
- Utilized sugar absorption tests for intestinal permeability.
Main Results:
- MBI occurred in 55% of chemotherapy cycles, correlating with DGS.
- Fecal human DNA/total DNA ratio and plasma citrulline correlated with NCI criteria and DGS.
- Plasma IL-8 showed a strong correlation with plasma citrulline.
Conclusions:
- MBI is reflected by inflammation (IL-8) and cell loss markers (plasma citrulline, fecal human DNA/total DNA).
- Plasma citrulline is a potential biomarker for MBI in children.
- Further research is required to validate plasma citrulline for MBI assessment in pediatric oncology.
Background:
The currently used National Cancer Institute (NCI) adverse events criteria for mucosal barrier injury (MBI) are insufficient for use in children. We searched for objective, easily measurable indicators for MBI in children with cancer.
Purpose:
In children with acute myeloid leukemia, various MBI-related clinical and laboratory tests were investigated, reflecting clinical severity (NCI symptomatic adverse events criteria (gold standard), daily gut score (DGS)), inflammation (plasma and fecal interleukin-8 (IL-8), fecal calprotectin), enterocytic loss (plasma citrulline, ratio fecal human DNA/total DNA) and intestinal permeability (sugar absorption tests).
Results:
Intestinal MBI as detected by the NCI adverse events criteria was found in 55% of chemotherapy cycles, correlating well with the continuous DGS (n = 55, rho = 0.581; P < 0.001). Intestinal cell loss as measured by the ratio fecal human DNA/total DNA and plasma citrulline correlated well with both NCI criteria (n = 61, rho = 0.357, P = 0.005 resp. n = 58, rho = -0.482; P < 0.001) and DGS (n = 54, rho = 0.352, P = 0.009 resp. n = 55, rho = -0.625; P < 0.001). Plasma IL-8 correlated strongly to plasma citrulline (n = 46, rho = -0.627; P < 0.001).
Conclusions:
MBI was reflected by parameters indicating inflammation (IL-8) and cell loss (plasma citrulline, ratio fecal human DNA/total DNA). We conclude that plasma citrulline might be a good parameter for MBI. Further studies are needed to show whether plasma citrulline can be used as a marker for MBI in future research.
