Changes in serum citrulline during hematopoietic cell transplantation (HCT) in children

Abstract

Children undergoing HCT may experience gastrointestinal side effects that limit oral intake and enteral absorption. Serum citrulline (CIT), a non‐essential amino acid produced by small bowel enterocytes, is a marker of intestinal mass. We sought to determine if serum CIT was associated with clinical markers of gastrointestinal health in children undergoing HCT. We conducted a multi‐center, prospective cohort study of 26 children to define time related changes in serum CIT over the course of HCT. Enteral intake, emesis, days on parenteral nutrition, stool volume, IL‐6 levels, and oral mucositis severity were measured. Weekly serum CIT concentrations were obtained from 10 days prior until 30 days after HCT. Mean baseline CIT concentration was 25.1 μmol/L (95% CI 7.5–83.5), decreasing to a nadir on day +8 that was lower with severe oral mucositis (6.2 μmol/L, 95% CI 3.1– 12.2) than without (11.5 μmol/L, 95% CI 5.5–23.9), before returning to baseline by day 30 (p=0.005). CIT was inversely associated with IL‐6 (1% lower CIT per 10% increase in IL‐6, p=0.016) but was not correlated with TNF‐alpha, leptin, or ghrelin. In children undergoing HCT, serum CIT is valid marker for oral mucositis severity and may indicate more extensive mucosal injury to the gastrointestinal tract. Supported by the Massachusetts Vitamin Litigation Grant and NIH grants M01‐RR02172, UL1 RR025758–01, M01‐RR00865, M01‐RR00188, and K24 HD 058795.