ASPO Abstracts
Differences in Treatment Outcomes in Children who Experienced Methotrexate-related Neurotoxicity while Receiving Acute Lymphoblastic Leukemia Therapy
Category: Survivorship & Health Outcomes/Comparative Effectiveness Research, Cancer Health Disparities
Conference Year: 2018
Abstract Body:
Purpose: Our objective was to evaluate the impact of methotrexate (MTX)-related neurotoxicity (NT) on therapy in a multi-institutional prospective cohort of pediatric patients (2-17 years old) with acute lymphoblastic leukemia (ALL). Methods: Suspected NT cases were defined as patients with a neurologic event following intrathecal (IT) and/or intravenous (IV) MTX that led to a change in subsequent MTX therapy. Multivariable linear regression models were generated to compare treatment differences between patients with and without MTX NT. The frequency of all-cause and central nervous system (CNS) relapse was compared between patients with and without MTX NT using the log-rank test and Cox regression models. Results: Of the 280 patients enrolled, 39 (13.9%) experienced MTX NT (median follow-up = 22.6 months; range: 1.3 - 55.6 months). Importantly, 74% of patients experiencing NT were Hispanic (compared to 44% among those without NT, p <0.001). Independent of treatment risk arm, sex, and age at diagnosis, patients who experienced MTX NT received an average of 2.25 (95% CI: 1.73-2.77) fewer doses of IT MTX. Six of the 39 cases of MTX NT (15.4%) experienced relapse during the study period, compared to 13 of the 241 (2.1%) patients without MTX NT (log-rank p = 0.0038). CNS relapse was significantly more frequent among patients with MTX NT (10.3%) than patients without NT (2.1%; log-rank p = 0.0014). In univariate Cox regression models, MTX NT was significantly associated with CNS relapse (unadjusted HR: 3.80, 95% CI: 1.44-10.02), a trend which remained after individually accounting for treatment risk arm (HR: 2.92, 95% CI: 1.07-7.95), MRD status at day 29 (HR: 3.49, 95% CI: 1.32-9.24), race and ethnicity (HR: 3.15, 95% CI: 1.13-8.79), age at diagnosis (HR: 2.56, 95% CI: 0.91-7.21), and gender (HR: 3.82, 95% CI: 1.44-10.10). Conclusion: We identified an increased risk of CNS relapse among ALL patients following MTX NT, which was not fully explained by other clinical or demographic risk factors. Further, incidence of NT was higher among Hispanic patients in our clinics. Future studies will examine pharmacogenetics related to MTX metabolism, especially among Hispanic patients, who experience worse treatment outcomes despite having more favorable disease characteristics
Keywords: Neurotoxicity, Leukemia, Methotrexate, Treatment Outcomes