Monitoring of citrulline and diamine oxidase levels as biomarkers for intestinal mucositis during early-phase hematopoietic cell transplantation

BACKGROUND: Gastrointestinal tract mucositis is a common side effect in the early phase of hematopoietic cell transplantation (HCT), although reliable biomarkers have not yet been established. Since blood levels of citrulline and diamine oxidase (DAO) have been reported as specific markers of intestinal mucosal injury during cytotoxic cancer chemotherapy, we aimed to evaluate the relationship between circulating citrulline/DAO levels and the severity of gastrointestinal mucosal injury in patients with hematologic diseases who had undergone various types of HCT. METHODS: Forty patients who received autologous (n=21) and allogeneic HCT (n=19; cord blood (n=16), peripheral blood (n=3)) were enrolled in the study. Serial monitoring of plasma citrulline and serum DAO levels was prospectively performed from the day prior to the start of the conditioning regimen until day 28 post-HCT. RESULTS: Citrulline and DAO levels significantly decreased after the start of conditioning. The recovery of citrulline and DAO levels tended to be delayed in cord blood transplant recipients, compared with autologous and allogeneic peripheral blood transplant groups, probably reflecting the severity of mucosal injury during the prolonged neutropenic period. The nadir levels for both markers were inversely associated with peak C-reactive protein levels. DISCUSSION: There was a slight difference in the time-dependent courses of these biomarker levels between each type of HCT. The change of DAO levels was more parallel to the clinical parameters. Serially monitored citrulline and DAO levels may be promising biomarkers for assessing intestinal mucosal injury in the early phase of various types of HCT, although prospective studies including larger number of patients are warranted to confirm our observations.