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Updated: Aug 13, 2025
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Published on: February 9, 2016
Ethnic-specific predictors of neurotoxicity among patients with pediatric acute lymphoblastic leukemia after
Rachel D Harris1,2, Melanie Brooke Bernhardt1,2, Mark C Zobeck1,2
1Section of Hematology/Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
Background:
High-dose methotrexate (HD-MTX; 5000 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. This study evaluated risk factors for neurotoxicity after HD-MTX in an ethnically diverse population of patients with ALL.
Methods:
The authors retrospectively reviewed the medical records of patients who were diagnosed with ALL and treated with HD-MTX at Texas Children's Cancer Center (2010-2017). Methotrexate neurotoxicity was defined as a neurologic episode (e.g., seizures or stroke-like symptoms) occurring within 21 days of HD-MTX that resulted in methotrexate treatment modifications. Mixed effects multivariable logistic regression was used to estimate the odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between clinical factors and neurotoxicity.
Results:
Overall, 351 patients (58.1% Latino) who received 1183 HD-MTX infusions were evaluated. Thirty-five patients (10%) experienced neurotoxicity, 71% of whom were Latino. After adjusting for clinical risk factors, the authors observed that serum creatinine elevations ≥50% of baseline were associated with a three-fold increased odds (OR, 3.32; 95% CI, 0.98-11.21; p = .05) for neurotoxicity compared with 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 = .02) with serum creatinine elevation ≥50% compared with creatinine elevation <25%.
Conclusions:
The current findings indicate that serum creatinine elevations ≥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.
