Monitoring myeloablative therapy‐induced small bowel toxicity by serum citrulline concentration

Abstract

BACKGROUNDIntestinal mucositis is an important cause of cancer treatment‐related morbidity and mortality, carrying a serious economic burden. Currently, objective parameters are lacking that would enable the monitoring of gut damage in routine clinical practice, thus hindering the development of clinical studies designed to investigate potential new strategies aimed at reducing or preventing this side effect. The authors investigated the characteristics of serum citrulline concentration compared with sugar permeability tests with respect to its use as a marker for cancer treatment‐induced small bowel injury.METHODSIn this prospective study, 10 patients with hematologic malignancies who were receiving myeloablative therapy had gut toxicity assessed with sugar permeability tests. Serum citrulline concentrations also were determined using archival serum samples. The association between both parameters and their respective characteristics were analyzed and compared with data from the literature.RESULTSSensitivity and specificity were better for the citrulline assay compared with sugar permeability tests. Maximum gut damage assessed with the citrulline assay was observed 1–2 weeks earlier compared with the sugar permeability test. Similarly, citrulline indicated recovery of gut damage at 3 weeks after transplantation, whereas most sugar permeability tests remained abnormal.CONCLUSIONSThe simplicity of the method, the low costs, and the lack of drawbacks to the method make the citrulline assay the first choice for measuring and monitoring treatment‐related gut damage and provides an objective parameter for cancer treatment‐related gut toxicity. Cancer 2005. © 2004 American Cancer Society.

Intestinal mucosal dysfunction and infection during remission-induction therapy for acute myeloid leukaemia

“…1,29 The integrity of the oropharyngeal mucosa does not necessarily predict the state of distal tissues. 29 Our observations on a relatively small sample confirming previous reports 7,[15][16][17]21 are consistent with this hypothesis. In addition, our observations further re-enforce the independence of the chemotherapy-induced intestinal cytotoxicity and myelotoxicity.…”

“…12,13 The evaluation of drug-related treatment effects have focused primarily on visual estimates of the severity of oropharyngeal mucosa damage and upon nausea, vomiting, abdominal pain and diarrhoea as quantitative surrogates of gastrointestinal damage caudal to the oropharynx using a variety of operator-dependent quantitative and semiquantitative scoring systems. 1 More recently, functional measures of the integrity of the intestinal epithelial barrier using orally administered saccharide or radio-labelled probes have been applied to the study of gastrointestinal mucositis among haematopoietic stem cell transplant recipients 5,7,[14][15][16][17] and in acute myeloid leukaemia. [18][19][20][21] Intestinal permeability may be reflected by an elevated ratio of the concentration of lactulose to mannitol or rhamnose in fractional urinary excretion studies, 21,22 carrier-mediated transcellular absorption by the serum level of a five-carbon sugar, D-xylose, 18 and enterocyte mass by serum citrulline levels.…”

“…[18][19][20][21] Intestinal permeability may be reflected by an elevated ratio of the concentration of lactulose to mannitol or rhamnose in fractional urinary excretion studies, 21,22 carrier-mediated transcellular absorption by the serum level of a five-carbon sugar, D-xylose, 18 and enterocyte mass by serum citrulline levels. 17,22 There is limited experience using these functional assays as outcome measures for strategies to ameliorate cytotoxic therapyinduced intestinal damage. Accordingly, in the course of a randomized, double-blinded, placebo-controlled trial examining the protective effects of lisofylline, we attempted to temporally correlate standard assessments of clinical mucosal toxicity based upon the National Cancer Institute Common Toxicity Criteria 23 with idarubicin plus cytarabine-induced changes in absorption and permeability and infection in adult patients with newly diagnosed acute myeloid leukaemia undergoing remission-induction.…”

“…26 Although we were able to detect a significant lisofylline-related effect upon permeability, the effect upon xylose absorption was less dramatic. The use of additional probes such as sucrose, 33,34 radio-labelled ethylenaminediamine tetraacetic acid, 15,16 rhamnose, 21 O-methylglucose, 22 citrulline 17,22 or sucralose [34][35][36] might have enhanced the sensitivity for detecting differential treatment effects. Used concurrently, these probes offer the potential to study the differential site-specific damaging effects of cytotoxic therapy on the gastrointestinal mucosa.…”

Nutritional support in patients with GVHD of the digestive tract: state of the art

“…35 The authors also compared the plasma citrulline assay with sugar permeability tests in ten patients receiving myeloablative therapy, and showed plasma citrulline earlier detects maximum intestinal damage as well as recovery of the intestinal damage than sugar permeability tests. 36 Yet, no studies on plasma citrulline in patients with GVHD have been published. In summary, these small studies show that pancreatic atrophy may occur after allo-SCT, especially in patients with GVHD-DT (grade C), and so does exocrine pancreatic insuffiency in patients with GVHD(-DT) (grade C).…”