A Comparison of Somatic Mutations and ELN Classification in De Novo Acute Myeloid Leukemia between Appalachian and Non-Appalachian Kentucky

Introduction

The Appalachian region's cancer mortality rate is 10% higher than the national rate. Central Appalachia, which is predominantly in Kentucky, exceeds the national average by 35%. Appalachian Kentucky has higher mortality rates for prostate, lung, cervical, and head and neck cancers compared to non-Appalachian Kentucky. This can be attributed to health care disparities, environmental factors, and unique genomic characteristics of the tumors seen in the Appalachian population. Based on this, we hypothesized that patients with acute myeloid leukemia (AML) in Appalachian Kentucky would have worse outcomes and higher mutational burden compared to patients in non-Appalachian Kentucky. To test this hypothesis, we compared overall survival (OS) and frequency of molecular mutations between patients from Appalachian (ApK) and Non-Appalachian Kentucky (Non-ApK).

Methods

A single-center retrospective analysis was done utilizing the Kentucky Cancer Registry (KCR) to identify patients with De Novo AML from January 2015 to January 2021. Patients with available cytogenetic and somatic mutations profile from next-generation sequencing (NGS) were included. Demographic, clinical, laboratory, and pathologic data were obtained from clinical records. Statistical analysis was done using the Mann-Whitney U test for continuous variables and proportions were compared using Chi-square test. The Kaplan-Meier curves were used for overall survival.

Results

A total of 225 patients with de novo AML were identified. The median age at diagnosis was 61 (range, 21-86). The population was fairly distributed among males (52%) and females (48%). Approximately 56% (n=127) of patients were from ApK and 46% (n=98) were from non-ApK. Of the patients from ApK, approximately 22% (n=29) had favorable risk AML per the ELN 2022 classification, while 24% (n=30) had intermediate and 54% (n=68) had poor risk AML. This was not statistically different from the Non-ApK patients where 22% (n=22) had favorable, 21% (n=21) had intermediate, and 56% (n=55) of patients had poor risk AML (Table 1). The median number of clinically significant mutations were also similar between the two groups (p value = 0.47). The most commonly occurring somatic mutations were NPM1, DNMT3A and FLT3-ITD, which occurred at similar frequencies between the ApK and non-ApK cohorts. There was no difference in the median overall survival between the two cohorts (17 versus 22 months, p =0.47; 90% CI). Median OS and 1-year OS for the entire cohort were 21 months and 47.1%, respectively.

Conclusions

This study demonstrated that the outcomes of de novo AML is similar for patients from Appalachian versus Non-Appalachian Kentucky when treated at an Academic Medical Center. There were no statistically significant differences between ELN 2022 risk classification and mutational abnormalities tested between these two groups. This suggests that the biology in de novo AML is similar in both ApK and non-ApK patients.