The GvHD Hub uses cookies on this website. They help us give you the best online experience. By continuing to use our website without changing your cookie settings, you agree to our use of cookies in accordance with our updated Cookie Policy

Lower pre-transplant serum citrulline level as predictive marker for acute graft-versus-host disease

Jul 11, 2018

Armin Rashidiand colleagues from the University of Minnesota, Minneapolis, MN, USA, evaluated serum biomarkers of gut barrier as predictors of allogenic hematopoietic stem cell transplantation (allo-HSCT) outcomes. Three biomarkers (citrulline, regenerating islet-derived protein 3 alpha [Reg3a], and intestinal fatty acid binding protein [I-FABP]) were assessed pre-transplant on day -7, and then post-transplant on days 7 and 28 in consecutive patients undergoing allo-HSCT. The results of the study were publishedahead of print in Biology of Blood and Marrow Transplantationon 6 July 2018.

Patients and methods:

  • Allo-HSCT recipients: n = 95, median age = 58 years (range, 48–65)
  • Controls were healthy donors: n = 16, median age = 51 years (range, 37–56)
  • Assessed biomarkers:
    • Citrulline: total functional enterocyte mass
    • Reg3a: antibacterial activity of the gut
    • I-FABP: enterocyte turnover

Key findings:


  • Pre-HSCT biomarker levels were significantly different in patients vscontrols:
    • Citrulline: 1.88 (1.23–3.31) vs10 .8 (9.05–11.9) ng/mL, P< 0.01
    • Reg3a: 7.07 (4.81–11.30) vs4.70 (3.46–7.40) ng/mL, P= 0.006
    • I-FABP: 1.36 (0.78–1.83) vs 0.93 (0.74–1.18) ng/mL, P= 0.03
  • Intensity of the most recent preconditioning management, underlying disease, or HSCT-CI did not show correlation with pre-HSCT biomarkers
  • I-FABP and Reg3a showed a weak correlation: r = 0.23 (95% CI, 0.03–0.42)

Transplant outcomes and acute graft-versus-host disease (aGvHD)

  • Median follow-up = 12 months
  • 1-year non-relapse mortality (NRM): 13%, respectively
  • Higher Reg3a at day +7 predicted higher non-relapse mortality: 11.51 (9.43–19.99) vs4.20 (2.76–6.42) ng/mL, P< 0.001
  • 6-month aGvHD grade II-IV: 51%, respectively
  • Lower pre-HSCT citrulline correlated with higher risk of aGvHD grades II–IV: 1.64 (0.99–2.30) vs2 .70 (1.50–4.41) ng/mL, P< 0.01
  • Lower pre-HSCT citrulline level independently associated with a higher risk of aGVHD grade II-IV: HR = 1.32 (95%CI, 1.03–1.69), P= 0.02

Rashidi and colleagues concluded that these findings support that pre-HSCT serum citrulline level can serve as a predictive marker for patients with high risk for developing acute graft-versus-host disease. They further added that their results “suggest that pre-HSCT interventions to augment the gut barrier may decrease the risk of aGvHD.”

  1. Rashidi A. et al. Pre-transplant serum citrulline predicts acute graft-versus-host disease. Biology of Blood and Marrow Transplantation. 2018 July 06. DOI: 1016/j.bbmt.2018.06.036 .