Hispanic ethnicity is associated with prolonged clearance of high dose methotrexate and severe nephrotoxicity in children and adolescents with acute lymphoblastic leukemia

Mullikin, Dolores; Ranch, Daniel; Khalfe, Yasmin; Lucari, Brandon; Zobeck, Mark; Assanasen, Chatchawin; Gramatges, Maria M.; Scheurer, Michael E.; Schafer, Eric S.

doi:10.1080/10428194.2020.1783445

Cited by 8 publications

(13 citation statements)

References 13 publications

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“…Despite the notable strengths of our analysis, our study bears some limitations. The TCR does not collect individual clinical information known to affect survival, such as cytogenetic features, end-ofinduction minimal residual disease status, and increased treatmentrelated toxicities experienced by Hispanic children 48,49 ; as such, these could not be adjusted in our analyses. The TCR ascertains vital status by passive follow-up; therefore, whether patients migrated to and from the US-Mexico border area could not be determined.…”

Section: Although Previous Reports Have Observed Inferior Survival Formentioning

confidence: 99%

Ethnic disparities in childhood leukemia survival by border residence: A Texas population‐based analysis

Castellanos

Oluyomi

Chambers

et al. 2023

Cancer

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Background The US–Mexico border is a medically underserved region where survival disparities have been observed in adults diagnosed and treated for various malignancies. Studies examining survival disparities among children living in this region and diagnosed with cancer are lacking. The objective of this study was to evaluate the impact of border residence on survival among children with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and living near the Texas–Mexico border at the time of their diagnosis. The authors hypothesized that this group experiences inferior survival compared with patients with childhood leukemia living in nonborder areas. Methods The authors conducted a retrospective survival analysis leveraging data from the Texas Cancer Registry. The study included patients aged birth to 19 years who were diagnosed with ALL or AML between 1995 and 2017. Cox proportional hazards models were used to evaluate the factors associated with the risk of death. Overall survival estimates were calculated using Kaplan–Meier methods. Results During the study period, there were 6002 children diagnosed with ALL and 1279 diagnosed with AML. Inferior 5‐year overall survival was observed among children with ALL living along the border region compared with those living in nonborder areas (77.5% vs. 85.8%). In adjusted models, children with ALL living along the border experienced a 30% increased hazard of death versus children living in nonborder areas. In contrast, for children with AML, survival estimates did not vary by border versus nonborder residence. Conclusions Living along the border was associated with inferior survival among children with ALL, but not among children with AML. Additional studies are urgently needed to identify the factors driving these disparities to effectively design multilevel interventions and influence state and national cancer control programs.

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Section: Although Previous Reports Have Observed Inferior Survival Formentioning

confidence: 99%

Ethnic disparities in childhood leukemia survival by border residence: A Texas population‐based analysis

Castellanos

Oluyomi

Chambers

et al. 2023

Cancer

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“…In addition, there is growing evidence that methotrexate differentially affects Latino patients with ALL. For example, previous studies have reported a higher frequency of both delayed methotrexate clearance and methotrexate‐related neurotoxicity among Latino children compared with non‐Latino White children 2,10 . Because methotrexate‐related toxicity may adversely affect the delivery of curative therapy and compromise treatment efficacy, ethnic differences in methotrexate toxicities may contribute to the well characterized disparities in ALL relapse and survival experienced by Latino children with ALL 8,11,12 .…”

Section: Introductionmentioning

confidence: 99%

“…When given in highdoses (i.e., 5000 mg/m 2 ), methotrexate provides added protection against central nervous system (CNS) relapse and significantly improves survival in patients who have B-lineage ALL (B-ALL) with high-risk disease. [1][2][3][4] However, high-dose methotrexate (HD-MTX) can result in dose-limiting neurotoxicity, with a reported incidence among patients with pediatric ALL ranging between 3% and 14%. 1,5,6 Although acute symptoms are typically transient, neurotoxicity can be both critical and enduring, often resulting in methotrexate treatment modifications.…”

Section: Introductionmentioning

confidence: 99%

“…For example, previous studies have reported a higher frequency of both delayed methotrexate clearance and methotrexaterelated neurotoxicity among Latino children compared with non-Latino White children. 2,10 Because methotrexate-related toxicity may adversely affect the delivery of curative therapy and compromise treatment efficacy, ethnic differences in methotrexate toxicities may contribute to the well characterized disparities in ALL relapse and survival experienced by Latino children with ALL. 8,11,12 Recognizing these important disparities, the objectives of this study were: (1) to evaluate clinical predictors of methotrexate-related neurotoxicity after HD-MTX and (2) to assess whether the prognostic potential of these factors differed between racial and ethnic groups.…”

Section: Introductionmentioning

confidence: 99%

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

Harris

Bernhardt

Zobeck

et al. 2023

Cancer

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Background: High-dose methotrexate (HD-MTX; 5000 mg/m 2 ) 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)(2011)(2012)(2013)(2014)(2015)(2016)(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 <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%. Conclusions:The current findings indicate that serum creatinine elevations ≥50% may be associated with an increased risk for neurotoxicity among Latino childrenThe last two authors contributed equally to this article as senior authors.

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“…8,9 Despite these efforts, clinically useful models for predicting toxicity are still nascent, and considerable interindividual variability remains unaccounted for in the pharmacokinetic models, suggesting further research into risk factors for toxicity is needed to improve the precision of predictions. Racial and ethnic subpopulations with differential toxicity rates from MTX, such as Hispanic patients, 10,11 are not well represented in prior analyses, introducing potential bias in model predictions.…”

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confidence: 99%

Novel and replicated clinical and genetic risk factors for toxicity from high‐dose methotrexate in pediatric acute lymphoblastic leukemia

et al. 2023

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Methotrexate (MTX) is a key component of treatment for pediatric acute lymphoblastic leukemia (ALL). Many effective ALL regimens include multiple administrations of MTX in doses that may cause life-threatening adverse effects such as gastrointestinal inflammation, hepatitis, kidney injury, and myelosuppression. These toxic side effects may increase the risk of infections, organ dysfunction, treatment delays, and poor treatment outcomes. MTX doses ≥1000 mg/m 2 are commonly given in the hospital with aggressive supportive care and therapeutic drug monitoring to decrease these risks. Many patients do not clear the drug as expected, which results in prolonged hospitalizations and increased health care costs.

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Hispanic ethnicity is associated with prolonged clearance of high dose methotrexate and severe nephrotoxicity in children and adolescents with acute lymphoblastic leukemia

Cited by 8 publications

References 13 publications

Ethnic disparities in childhood leukemia survival by border residence: A Texas population‐based analysis

Ethnic disparities in childhood leukemia survival by border residence: A Texas population‐based analysis

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

Novel and replicated clinical and genetic risk factors for toxicity from high‐dose methotrexate in pediatric acute lymphoblastic leukemia

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