Publication Date

4-15-2023

Journal

Cancer

DOI

10.1002/cncr.34646

PMID

36692972

PMCID

PMC10625847

PubMedCentral® Posted Date

4-15-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Child, Humans, Methotrexate, Antimetabolites, Antineoplastic, Creatinine, Retrospective Studies, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neurotoxicity Syndromes, pediatrics, acute lymphoblastic leukemia, methotrexate, toxicity, neurotoxicity, chemotherapy

Abstract

High-dose methotrexate (HD-MTX; 5,000 mg/m2) is an important component of curative therapy in many treatment regimens for high-risk pediatric acute lymphoblastic leukemia (ALL). However, methotrexate therapy can result in dose-limiting neurotoxicity which may disproportionately affect Latino children. Thus, we evaluated risk factors for neurotoxicity in an ethnically diverse population of 351 patients (58.1% Latino) who received 1,183 HD-MTX infusions. Overall, thirty-five patients (10%) experienced neurotoxicity, 71% of whom were Latino. After adjusting for clinical risk factors, we found that serum creatinine elevations ≥50% of baseline were associated with a 3-fold increased odds (OR = 3.32, 95% CI: 0.98-11.21, p=0.05) for neurotoxicity when compared to creatinine elevation <25%. Notably, predictors of neurotoxicity differed by ethnicity. Specifically, Latino children experienced a nearly six-fold increase in neurotoxicity odds (OR = 5.80, 95% CI: 1.39-24.17, p=0.02) with serum creatinine elevation ≥50%, compared to creatinine elevation <25%. Thus, serum creatinine elevation ≥50% may be associated with an increased risk for neurotoxicity among Latino children with ALL and may identify potential candidates for therapeutic or supportive care interventions.

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