Pronounced Reductions in Plasma Citrulline Indicate Severe Intestinal Mucosal Barrier Injury During Induction Therapy
Carla Warley Kjær1, Maria Ebbesen Sørum1, Silvia De Pietri1,2
1Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Insights
Pediatric acute myeloid leukemia (AML) chemotherapy causes significant mucosal barrier injury, linked to inflammation and infections. This damage may be a target for new supportive treatments in children with AML.
Area of Science:
- Pediatric oncology
- Gastroenterology
- Infectious diseases
Background:
- Chemotherapy for pediatric acute myeloid leukemia (AML) often leads to fever, inflammation, and bloodstream infections (BSI).
- The role of mucosal barrier injury in these complications in children with AML has not been studied.
- Plasma citrulline is a biomarker for intestinal mucosal integrity.
Purpose of the Study:
- To assess mucosal barrier injury in children undergoing AML chemotherapy using plasma citrulline levels.
- To investigate the association between mucosal barrier injury and systemic inflammation, fever, and BSI during AML treatment.
Main Methods:
- A prospective study of 20 children (aged 1-16 years) with AML undergoing two induction chemotherapy courses (NOPHO-DBH AML 2012 protocol).
- Plasma citrulline levels were measured weekly from day 1 to day 29 of each induction course.
- Associations between citrulline levels, C-reactive protein (CRP), fever, and BSI were analyzed.
Main Results:
- All patients showed significant reductions in plasma citrulline during chemotherapy, with nadir around day 15.
- Elevated CRP levels and fever were common, occurring in 19/20 and all patients, respectively.
- Severe mucosal damage correlated with higher CRP and more febrile days; BSI was associated with lower citrulline levels later in induction.
Conclusions:
- Pediatric AML treatment induces substantial mucosal barrier injury.
- This injury is significantly associated with inflammatory and infectious complications during treatment.
- Targeting mucosal barrier integrity could be a potential strategy for supportive care interventions in pediatric AML.
Objectives:
Pediatric acute myeloid leukemia (AML) chemotherapy regimens are frequently burdened by fever episodes, systemic inflammation and bloodstream infections (BSI). Mucosal barrier injury may contribute to these complications, but its role in childhood AML remains uninvestigated. This study assessed mucosal barrier injury using plasma citrulline and examined associations with inflammation, fever, and BSI.
Methods:
Twenty children (1-16 years) with AML were prospectively studied during two induction courses (NOPHO-DBH AML 2012 protocol). Plasma citrulline was measured weekly from days 1-29 of each course.
Results:
All patients exhibited marked reductions in citrulline during both inductions, reaching nadir on day 15 and recovering by day 29. C-reactive protein (CRP) levels > 50 mg/L occurred in 19/20 patients, and 10/20 developed BSI. Fever occurred in all patients during induction I and in 16/19 during induction II. Severe mucosal damage (citrulline AUC) correlated with higher CRP and more febrile days, particularly in induction II (rs = -0.72, p = 0.0011; rs = -0.47, p = 0.06). Patients with BSI showed lower citrulline on days 22 and 29 following induction II (11.1 vs. 16.2 μM, p = 0.024) and (10.1 vs. 17.3 μM, p = 0.012).
Conclusions:
Pediatric AML treatment causes significant mucosal barrier injury, which is associated with inflammatory and infectious complications and may represent a target for supportive interventions.
