The effect of high-dose methotrexate chemotherapy on citrulline level to gastrointestinal mucositis cases in children with acute lymphoblastic leukemia during the consolidation phase

Acute Lymphoblastic Leukemia (ALL) is the most common pediatric malignancy, with survival rates exceeding 90% due to advancements in chemotherapy, including high-dose methotrexate (HD-MTX). However, gastrointestinal (GI) mucositis remains a significant complication, impairing treatment continuity and quality of life. Citrulline, a biomarker synthesized in enterocytes, reflects intestinal integrity and offers a non-invasive alternative for monitoring mucosal damage. This study aimed to evaluate citrulline dynamics in children with ALL undergoing HD-MTX chemotherapy during the consolidation phase. This cross-sectional study included 34 pediatric ALL patients in consolidation phase. Serum citrulline levels were measured pre- and post-HD-MTX chemotherapy using high-performance liquid chromatography. Mucositis severity was assessed using the National Cancer Institute Common Terminology Criteria. Data analysis involved paired t-tests and subgroup comparisons by risk stratification (Standard Risk [SR], High Risk [HR]) and mucositis grades. Overall, no significant changes in serum citrulline levels were observed post-chemotherapy. SR patients exhibited a significant decline in citrulline levels, consistent with mucosal injury. Conversely, HR patients demonstrated an unexpected increase in citrulline, potentially due to compensatory enterocyte responses or altered metabolism. Grade 1 mucositis patients showed increased citrulline levels, indicating early recovery, while grade 2 mucositis patients showed no significant changes, reflecting sustained injury. Citrulline is a promising biomarker for monitoring chemotherapy-induced GI mucositis in pediatric ALL patients. Its non-invasive measurement and correlation with mucosal health highlight its potential for improving personalized care. Further validation in diverse populations is required to optimize its clinical application.