Pronounced Reductions in Plasma Citrulline Indicate Severe Intestinal Mucosal Barrier Injury During Induction Therapy for Pediatric Acute Myeloid Leukemia.

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.