Association of genetic variants and survival in patients with acute myeloid leukemia in rural Appalachia.

Abstract

e19022 Background: Many previous population health studies examining adults with acute myeloid leukemia (AML) are derived from national databases within large urban centers. To address the concern of under-representation of rural Appalachian population in cancer genomic databases, we performed exploratory whole exome sequencing in patients with newly diagnosed AML. As the only stem cell transplantation center in the state, WVU is uniquely situated to capture most of these patients from the state and surrounding area. Due to its unique industry and environmental exposures, we hypothesized that WV may have both different rates of mutations and differing outcomes than the nation as a whole. Methods: We performed whole exome sequencing on 26 patients with newly diagnosed AML from paired bone marrow and buccal samples that were obtained from 2015 to 2017. Whole exome sequencing libraries were prepared using Agilent SureSelect Human Whole Exome technology. The libraries were sequenced on an Illumina HiSeq1500 sequencer using paired end runs. Correlations between genetic variants and clinical outcome variables were examined via retrospective chart review. Variables measured included association between biomarker data and progression-free survival (PFS) and overall survival (OS). Results: Median patient age was 68 years and women represented 10 of the patients (37%). Twenty-one patients had de novo AML (84%), 3 patients had preceding MDS (12%), and 1 patient had therapy-related AML (4%). As per ELN criteria, 8 patients were favorable (32%), 12 were intermediate (48%), and 5 were adverse risk (20%). Eight patients proceeded to transplant with the following donors: 4 MUD (50%), DUCB (37.5%), and 1 haploidentical (12.5%). The median PFS and OS were 16.5 months and 26.6 months, respectively. Tobacco use was the largest known exposure with 7 patients. We noted a similar mutational trend compared to national TCGA data, except for an increased tumor mutation burden and higher frequency of the following mutations as seen in Table. Neither MUC3A or MUC5AC were identified in the TCGA database. Of our five patients with BCOR mutations, two had a co-existing FLT3-ITD mutation, one of which also had a NPM1 mutation. Two patients had secondary AML, while the other 3 had de novo disease. The median OS was 63 days. While not statistically significant, BCOR mutation was trending toward a poor prognostic indicator.Conclusions: Despite our small patient cohort, the findings provide further assessment of predisposing detrimental mutations in AML in the Appalachian region and associated survival outcomes.[Table: see text]