Ethnic‐specific predictors of neurotoxicity among patients with pediatric acute lymphoblastic leukemia after high‐dose methotrexate

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 Lat...

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Published in:Cancer 2023-04, Vol.129 (8), p.1287-1294
Main Authors: Harris, Rachel D., Bernhardt, Melanie Brooke, Zobeck, Mark C., Taylor, Olga A., Gramatges, Maria Monica, Schafer, Eric S., Lupo, Philip J., Rabin, Karen R., Scheurer, Michael E., Brown, Austin L.
Format: Article
Language:English
Subjects:
Acute lymphoblastic leukemia
Antimetabolites, Antineoplastic - therapeutic use
chemotherapy
Child
Children
Confidence intervals
Creatinine
Health services
Humans
Immunomodulators
Leukemia
Lymphatic leukemia
Medical records
Methotrexate
Minority & ethnic groups
Neurotoxicity
Neurotoxicity Syndromes - epidemiology
Neurotoxicity Syndromes - etiology
Oncology
Patients
Pediatrics
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma - epidemiology
Retrospective Studies
Risk factors
Seizures
Statistical analysis
toxicity
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Summary: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
ISSN:0008-543X
1097-0142
DOI:10.1002/cncr.34646