Assessment of pre- and post-transplant concentrations of citrulline, zonulin, and calprotectin in children undergoing allogeneic hematopoietic cell transplantation

Abstract

Background

Allogeneic hematopoietic cell transplantation (allo-HCT) is a life-saving treatment for pediatric patients but is often associated with severe gastrointestinal complications. Identifying reliable biomarkers of gut integrity and inflammation is crucial for early detection and management of these issues. This study evaluates pre- and post-transplant levels of citrulline, zonulin, and calprotectin in pediatric allo-HCT patients.

Methods

A prospective cohort study was conducted on 100 pediatric patients at the Children’s Hospital from 2023 to 2025. Citrulline, zonulin, and calprotectin levels were measured at baseline (pre-transplant), 3 months, and 6 months post-transplant.

Results

Calprotectin and zonulin levels peaked at 3 months post-transplant (calprotectin: 123 ± 40 µg/g, p < 0.001; zonulin: 90.69 ± 20.32 ng/mL, p = 0.001) and declined by 6 months (calprotectin: 90.05 ± 30.27 µg/g; zonulin: 70.74 ± 15.38 ng/mL). Citrulline levels decreased from 25.49 ± 8.22 µM at baseline to 20.39 ± 5.52 µM at 6 months (p = 0.004). Elevated calprotectin and zonulin levels were strongly associated with severe GVHD (Grade III-IV: calprotectin 153.25 ± 51.81 µg/g, p = 0.001; zonulin 110.05 ± 25.33 ng/mL, p = 0.002) and higher grades of diarrhea and mucositis. Patients with obesity (BMI > 30) had significantly higher biomarker levels. Multiple hospital readmissions were also associated with elevated biomarker levels (p < 0.05).

Conclusion

Citrulline, zonulin, and calprotectin are promising biomarkers for assessing GI toxicity and inflammation in pediatric allo-HCT recipients. Their levels correlate with the severity of post-transplant complications, nutritional status, and clinical outcomes.