Clinical Risk Factors for High-Dose Methotrexate-Induced Oral Mucositis Following Individualized Dosing.

Area of Science:

• Pediatric Oncology
• Pharmacology
• Clinical Medicine

Background:

• Oral mucositis is a common side effect of high-dose methotrexate (HDMTX) in children with acute lymphoblastic leukemia (ALL).
• Despite personalized dosing strategies, variations in mucositis incidence persist, necessitating further investigation into risk factors.

Purpose of the Study:

• To identify risk factors associated with oral mucositis in children treated with individualized HDMTX protocols.
• To explore predictors of recurrent mucositis in this patient population.

Main Methods:

• Retrospective analysis of data from the St. Jude Children's Research Hospital total 16 trial.
• 1:1 case-control matching based on age, sex, risk classification, immunophenotype, and methotrexate course.
• Statistical analyses including McNemar's, Bowker's symmetry, and Wilcoxon signed-rank tests were employed.

Main Results:

• Significant associations were found between mucositis and skin rashes, fever, neutropenic fever, low absolute neutrophil count, acute kidney injury (AKI), delayed methotrexate clearance, and higher 42-h methotrexate levels.
• Independent predictors of mucositis included skin rashes, fever, and neutropenia.
• Female sex and AKI were associated with recurrent mucositis.

Conclusions:

• Skin rashes, fever, AKI, delayed methotrexate clearance, and elevated 42-h methotrexate levels are critical risk factors for HDMTX-induced oral mucositis.
• Skin rashes, fever, and neutropenia independently predict mucositis, while female sex and AKI are linked to recurrence.