Dataset Information

Disparities in pediatric acute myeloid leukemia (AML) clinical trial enrollment.

ABSTRACT: Equal access to clinical trial enrollment is important to ensure that findings are generalizable to the broader population. This study aimed to evaluate disparities in enrollment on pediatric oncology clinical trials. We assessed the relationship between patient characteristics and enrollment on COG trial AAML1031 in a cohort of pediatric patients with AML in the Pediatric Health Information System. The associations of enrollment with outcomes were evaluated. Non-Hispanic Black patients, infants, and patients from zip codes with a lower proportion of poverty were less likely to enroll (30% vs. 61%, p?=?.004; 34% vs. 58%, p?=?.003; 46% vs. 58%, p?=?.02). On-therapy mortality was similar among enrolled and nonenrolled patients (7.3% vs. 8.9%, p?=?.47). Differences in early mortality were more pronounced among nonenrolled patients compared to enrolled patients (3.0% vs. 0.5%, p?=?.03). Understanding the etiology of these disparities will inform strategies to ensure balanced access to clinical trials across patient populations.

SUBMITTER: Winestone LE

PROVIDER: S-EPMC6685754 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Disparities in pediatric acute myeloid leukemia (AML) clinical trial enrollment.

Winestone Lena E LE Getz Kelly D KD Rao Pooja P Li Yimei Y Hall Matt M Huang Yuan-Shung V YV Seif Alix E AE Fisher Brian T BT Aplenc Richard R

Leukemia & lymphoma 20190207 9

Equal access to clinical trial enrollment is important to ensure that findings are generalizable to the broader population. This study aimed to evaluate disparities in enrollment on pediatric oncology clinical trials. We assessed the relationship between patient characteristics and enrollment on COG trial AAML1031 in a cohort of pediatric patients with AML in the Pediatric Health Information System. The associations of enrollment with outcomes were evaluated. Non-Hispanic Black patients, infants ...[more]

PMID: 30732497

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Project description:BackgroundThere is growing evidence supporting a role for microRNAs (miRNA) as targets in aberrant mechanisms of DNA hypermethylation. Epigenetic silencing of tumor suppressor miRNAs, including miR-663, which has recently been reported to be inactivated by hypermethylation in several cancers, may play important roles in pediatric acute myeloid leukemia (AML). However, expression of miR-663 and its promoter methylation remain status unclear in childhood leukemia.MethodsPromoter methylation status of miR-663 was investigated by methylation specific PCR (MSP) and bisulfate genomic sequencing (BGS). Transcriptional expression of miR-663 was evaluated by semi-quantitative and real-time PCR, and the relationship between expression of miR-663 and promoter methylation was confirmed using 5-aza-2'-deoxycytidine (5-Aza) demethylation reagent.ResultsMiR-663 was aberrantly methylated in 45.5% (5/11) leukemia cell lines; BGS showed that the promoter was significantly methylated in three AML cell lines; methylation of miR-663 was significantly higher in Chinese pediatric AML patients [41.4% (29/70)] compared to normal bone marrow (NBM) control samples [10.0% (3/30)]. These results were confirmed by both BGS and 5-Aza demethylation analysis. In addition, miR-663 transcript expression was significantly lower in AML patients, both with and without miR-663 methylation, compared to controls; however, there were no significant differences in clinical features or French-American-British (FAB) classification between patients with and without miR-663 methylation.ConclusionsExpression of miR-663 was significantly lower in pediatric AML cells compared to NBM controls; furthermore, a high frequency of miR-663 promoter hypermethylation was observed in both AML cell lines and pediatric AML samples. Inactivation of miR-663 by promoter hypermethylation could be affected by 5-Aza demethylation. These findings suggest that hypermethylation of the miR-663 promoter may be an early event in the development of pediatric AML.

Dataset Information

Disparities in pediatric acute myeloid leukemia (AML) clinical trial enrollment.

Publications

Disparities in pediatric acute myeloid leukemia (AML) clinical trial enrollment.

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