Latino Children With Cancer May Be at an Increased Risk for Neurotoxicity

Latino children with acute lymphoblastic leukemia who are treated with methotrexate tend to experience neurotoxicity at a higher rate than their non-Latino cohorts, but findings from recent research may help predict which children are more likely to experience the side effect.

Higher levels of serum creatine were associated with increased risk for neurotoxicity. Creatine is a chemical compound leftover from energy-producing processes in the muscles — a high level may indicate poor kidney function.

High-dose methotrexate is an important part of curative therapy in various treatment regimens for high-risk pediatric acute lymphoblastic leukemia; however, the therapy can cause neurotoxicity, which is often disproportionately observed in Latino children.

“Although acute symptoms are typically transient, neurotoxicity can be both critical and enduring, often resulting in methotrexate treatment modifications,” the study authors wrote. “These modifications may include either dose omissions or complete eliminations of methotrexate, which potentially diminish treatment efficacy.”

However, clinical predictors of neurotoxicity caused by this therapy are limited.

“Clinical predictors of methotrexate neurotoxicity are poorly defined, which is a major barrier to the development and delivery of neurotoxicity prevention and supportive care interventions,” they wrote.

So, researchers sought to evaluate risk factors for neurotoxicity after methotrexate treatment in an ethnically diverse population of patients with acute lymphoblastic leukemia.

The study, which was published in the journal Cancer, included 351 patients — 58.1% were Latino — who received methotrexate therapy. A total of 35 patients (10%) experienced neurotoxicity, 71% of them were Latino.

After adjusting for clinical risk factors, serum creatine elevations at 50% or higher were associated with a threefold increased risk for neurotoxicity compared to those under 25%. For Latino children, this risk was increased to almost six-fold, although this was not statistically significant.

Most of the patients presented with stroke-like symptoms, seizures, altered mental status or aphasia, vision changes or muscle weakness and/or numbness.

These results are consistent with those that are previously reported indicating that Latino children are at a higher risk of toxicity because of methotrexate.

“The current findings indicate that serum creatine elevations >50% may be associated with an increased risk of neurotoxicity among Latino children with acute lymphoblastic leukemia and may identify potential candidates for therapeutic or supportive care interventions,” the study authors wrote.

Of note, this study was retrospective meaning researchers evaluated studies that were previously done and only at one institution, one of the limitations of the study. And because the data was pooled from medical records specifics of neurotoxicity severity were limited.

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