Distance Does Not Matter: Excellent Survival Outcomes for Leukemia Patients in Rural Appalachia
Authors: Isaac Krista , Reed Daniel R , Desai Raj Piyush , Williams Eli , Balkrishnan Rajesh , Keng Michael K , Ballen Karen K. 
Published: November 2019

Background: Rural communities may not have access to adequate health care, but the effect of geographic residence on patient outcomes and molecular characteristics of acute myeloid leukemia (AML) is poorly understood. Several studies have investigated the effect of various demographics (such as race, gender, zip code) and environmental exposures on the development and outcome of AML. Evidence is lacking to suggest a link between genetic abnormalities and residence.
Methods: A single center, retrospective chart review was conducted on patients with AML diagnosed between 9/2015 and 8/2018. Consecutive patients with a new diagnosis of AML and a clinical next generation sequencing panel (Illumina TruSight Myeloid 54 gene panel) performed during their initial leukemia workup were included. Patients were excluded if they had APML or CML in blast crisis. Data collected included demographic information (including zip code), smoking history, BMI, cytogenetic data, treatment regimen, and overall survival. Patients were grouped into urban and rural subsets based on their county of residency as described in the National Center for Health Statistics 2013 Urban-Rural Classification Scheme for Counties. Zip codes were used to extrapolate socioeconomic data including education and income level. Cytogenetic data was used to risk stratify patients per ELN criteria. Mutational profile, cytogenetics and overall survival (OS) were compared between the groups. Mutations analyzed were limited to ASXL1, DNMT3A, FLT3, IDH1, IDH2, NPM1, NRAS, TET2, and TP53, as these are often used in medical decision making. Multivariate logistic regression was conducted to evaluate differences between the groups. Time to event data were analyzed using log-rank tests, Kaplan-Meier method, and Cox proportional hazard regression model.
Results: 113 patients were included in this study. Median age of the entire cohort was 66.3 years old. 59% (n = 67) were male. 24% (n = 27) of patients were from a rural area; 76% (n = 86) were from an urban area. There was no difference in median age, race, prior MDS or MPN, number of patients who underwent chemotherapy or number of patients who underwent allogeneic stem cell transplant (ASCT) as demonstrated in Table 1. Patients from both cohorts also had similar risk cytogenetics (urban cohort: favorable: n = 5, 5.8%; intermediate: n = 35; 40.7%; adverse: n=46; 53.5%; rural cohort: favorable: n = 3, 11.1%; intermediate: n = 14; 51.9%; adverse: n = 10, 37%; p = 0.282). In the rural cohort, 15% of patients reported income below the poverty level; in the urban cohort, 10.2% reported income below the poverty level (p < 0.0001). Fewer patients in the rural cohort were high school graduates as compared to the urban cohort (82.7% versus 87.8%, p < 0.0001). Rural patients traveled an average of 145 miles for treatment; urban patients traveled 57 miles (p < 0.0001).
Mutation frequency is described in Table 2. ASXL1 mutation was more frequent in the urban cohort as compared to the rural cohort (p = 0.032). There was no difference in frequency of other mutations between the cohorts.
The 2 year survival rate was 46% (n = 52) for the cohort; 2 year survival rate for the rural cohort was 70% (n = 19) and for the urban cohort was 38% (n = 33) (p = 0.011; Figure 1). 53 patients (urban: n =39, 66.1%; rural: n = 14, 77.8%; p = 0.35) underwent induction chemotherapy. Rural patients who underwent induction chemotherapy had an improved OS as compared to urban patients who underwent induction chemotherapy (p = 0.005).
Conclusion: In this single center retrospective study, our data demonstrates: 1. Urban patients had an increased frequency of ASXL1 mutations; 2. Rural patients were more likely to live below the poverty level and not graduate high school; 3. Rural patients traveled a greater distance for treatment; 4. OS was improved in rural patients in this limited cohort. Our rural patients may have improved OS due to our close co-management with rural centers. These studies suggest that the biology of the AML is not worse in the rural cohort and intensive efforts at access, remote monitoring, and communication with local physicians may result in outcomes similar to urban patients. Further studies will be investigating improving access to leukemia and transplant care for patients with AML.

Disclosures
Balkrishnan: Merck and Company: Consultancy. Keng:Agios: Membership on an entity's Board of Directors or advisory committees.