Citrulline and albumin as biomarkers for gastrointestinal mucositis in recipients of hematopoietic SCT

Abstract

The NCI Common Terminology Criteria for Adverse Events v3.0 is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term.

Early post-transplant contrast-enhanced abdominopelvic CT scan predicts the risk of subsequent acute GvHD

“…14-16 Low levels of serum albumin have been shown in previous studies to correlate with regimen-related toxicity and predict higher transplant-related mortality. 3, 17 The correlation between low albumin and mesenteric edema in our study may be explained by one or both of the following mechanisms: ( i ) direct effect of low albumin causing fluid extravasation, ( ii ) intestinal barrier damage causing both mesenteric inflammation/edema and protein enteropathy resulting in albumin loss. Also, albumin is a “negative acute-phase protein”, thus low albumin levels may reflect the acute inflammation (i.e.…”

“…The preference for doing the CT during the period between Days +7 and +14 post-SCT was according to previous data suggesting maximal gut damage about two weeks after initiation of conditioning. 2, 3 The specific day chosen for the CT was based on logistical factors. CT scoring was based on six characteristics: vasa recta engorgement (yes: 1, no: 0), gallbladder fossa edema (yes: 1, no: 0), mesenteric edema (yes: 1, no: 0), gallbladder/biliary enhancement (none: 0, mild: 1, moderate: 2, severe: 3), bowel wall thickening/enhancement (none: 0, mild: 1, moderate: 2, severe: 3), and number of involved bowel loops (none: 0, one loop: 1, two loops: 2, three or more loops: 3).…”

Gastrointestinal Safety Pharmacology in Drug Discovery and Development

“…The circulating level of citrulline gives an accurate reflection of small bowel enterocyte mass and is, therefore, an accurate biomarker of functional small bowel enterocytes (Lutgens and Lambin 2007). Citrulline has been studied in the context of gastrointestinal toxicity following cancer treatment and has been found to correlate with oral mucositis and altered gut integrity following hematopoietic stem cell transplantation, maximum gut damage following total body irradiation, and gastrointestinal mucosal barrier injury in pediatric patients following chemotherapy (Blijlevens et al 2004;van der Velden 2013;Lutgens et al 2005;van Vliet et al 2009). Given that this is a marker of small bowel enterocyte mass not inflammation, it may well have a role in monitoring chronic radiation-related injury to the gastrointestinal tract, which is a fibrotic, noninflammatory process.…”

The Use of Circulating Biomarkers in Early Clinical Trials in Patients With Cancer

“…In response to mucosal injury following radiotherapy, mechanism-based agents and chemotherapy circulating levels of citrulline fall rapidly [96][97][98][99]. Citrulline levels are accurate monitors of small bowel function and outperform other potential biomarkers of small bowel toxicity such as fecal lactoferrin or sugar permeability tests in the assessment of chemotherapy-induced small bowel toxicity [99,100].…”