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Disparities in Neurotoxicity Risk and Outcomes among Pediatric Acute Lymphoblastic Leukemia Patients.

Publication ,  Journal Article
Taylor, OA; Brown, AL; Brackett, J; Dreyer, ZE; Moore, IK; Mitby, P; Hooke, MC; Hockenberry, MJ; Lupo, PJ; Scheurer, ME
Published in: Clinical cancer research : an official journal of the American Association for Cancer Research
October 2018

Purpose: Methotrexate chemotherapy can be associated with neurologic complications during therapy and long-term neurologic deficits. This study evaluated demographic and clinical factors associated with incidence of methotrexate neurotoxicity and described the impact of neurotoxicity on acute lymphoblastic leukemia (ALL) therapy in pediatric patients.Experimental Design: Patients were enrolled between 2012 and 2017 from three pediatric cancer treatment centers in the United States. Medical records for suspected cases of methotrexate neurotoxicity, defined as an acute neurologic event following methotrexate therapy, were reviewed. Cox proportional hazards models were used to estimate the association between race/ethnicity and methotrexate neurotoxicity. Multivariable linear regression models compared treatment outcomes between patients with and without methotrexate neurotoxicity.Results: Of the 280 newly diagnosed patients enrolled, 39 patients (13.9%) experienced methotrexate neurotoxicity. Compared with non-Hispanic whites, Hispanic patients experienced the greatest risk of methotrexate neurotoxicity (adjusted HR, 2.43; 95% CI, 1.06-5.58) after accounting for sex, age at diagnosis, BMI Z-score at diagnosis, and ALL risk stratification. Patients who experienced a neurotoxic event received an average of 2.25 fewer doses of intrathecal methotrexate. Six of the 39 cases of neurotoxicity (15.4%) experienced relapse during the study period, compared with 13 of the 241 (2.1%) patients without neurotoxicity (P = 0.0038).Conclusions: Hispanic ethnicity was associated with increased risk of methotrexate neurotoxicity, which was associated with treatment modifications and relapse. Understanding the mechanism and predictors of methotrexate neurotoxicity is important to improving treatment outcomes in pediatric ALL. Clin Cancer Res; 24(20); 5012-7. ©2018 AACR.

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Published In

Clinical cancer research : an official journal of the American Association for Cancer Research

DOI

EISSN

1557-3265

ISSN

1078-0432

Publication Date

October 2018

Volume

24

Issue

20

Start / End Page

5012 / 5017

Related Subject Headings

  • United States
  • Risk Factors
  • Risk Assessment
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Patient Outcome Assessment
  • Oncology & Carcinogenesis
  • Nervous System Diseases
  • Methotrexate
  • Male
  • Incidence
 

Citation

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Taylor, O. A., Brown, A. L., Brackett, J., Dreyer, Z. E., Moore, I. K., Mitby, P., … Scheurer, M. E. (2018). Disparities in Neurotoxicity Risk and Outcomes among Pediatric Acute Lymphoblastic Leukemia Patients. Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, 24(20), 5012–5017. https://doi.org/10.1158/1078-0432.ccr-18-0939
Taylor, Olga A., Austin L. Brown, Julienne Brackett, ZoAnn E. Dreyer, Ida Ki Moore, Pauline Mitby, Mary C. Hooke, Marilyn J. Hockenberry, Philip J. Lupo, and Michael E. Scheurer. “Disparities in Neurotoxicity Risk and Outcomes among Pediatric Acute Lymphoblastic Leukemia Patients.Clinical Cancer Research : An Official Journal of the American Association for Cancer Research 24, no. 20 (October 2018): 5012–17. https://doi.org/10.1158/1078-0432.ccr-18-0939.
Taylor OA, Brown AL, Brackett J, Dreyer ZE, Moore IK, Mitby P, et al. Disparities in Neurotoxicity Risk and Outcomes among Pediatric Acute Lymphoblastic Leukemia Patients. Clinical cancer research : an official journal of the American Association for Cancer Research. 2018 Oct;24(20):5012–7.
Taylor, Olga A., et al. “Disparities in Neurotoxicity Risk and Outcomes among Pediatric Acute Lymphoblastic Leukemia Patients.Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, vol. 24, no. 20, Oct. 2018, pp. 5012–17. Epmc, doi:10.1158/1078-0432.ccr-18-0939.
Taylor OA, Brown AL, Brackett J, Dreyer ZE, Moore IK, Mitby P, Hooke MC, Hockenberry MJ, Lupo PJ, Scheurer ME. Disparities in Neurotoxicity Risk and Outcomes among Pediatric Acute Lymphoblastic Leukemia Patients. Clinical cancer research : an official journal of the American Association for Cancer Research. 2018 Oct;24(20):5012–5017.

Published In

Clinical cancer research : an official journal of the American Association for Cancer Research

DOI

EISSN

1557-3265

ISSN

1078-0432

Publication Date

October 2018

Volume

24

Issue

20

Start / End Page

5012 / 5017

Related Subject Headings

  • United States
  • Risk Factors
  • Risk Assessment
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Patient Outcome Assessment
  • Oncology & Carcinogenesis
  • Nervous System Diseases
  • Methotrexate
  • Male
  • Incidence