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.

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.

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%.

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.