Socioeconomic Disadvantage Is Associated with Decreased Long-Term Survival in Adolescent and Young Adult Patients with Acute Lymphoblastic Leukemia

Background:

The treatment of acute lymphoblastic leukemia (ALL) in the adolescent and young adult (AYA) population has dramatically improved over the past decade with the use of pediatric-inspired regimens increasing long-term survival rates to over 60%. Despite these advances, AYA patients with ALL have seen persistent disparities in survival by race and ethnic background. The primary objective of this study is to examine socioeconomic disadvantage as a driver of the racial and ethnic disparities that exist among AYAs with ALL using a nationally representative cancer registry.

Methods:

The cohort was identified using the SEER*Stat software, which utilizes Surveillance, Epidemiology, and End Results (SEER) data from the National Cancer Institute (NCI). All SEER patients diagnosed at age 15 to 39 years with ALL from January 1, 2005 to December 31, 2019 were included in the analysis. Patients were excluded from analysis if they had an unknown cause of death, were diagnosed with ALL only postmortem, had no survival time listed, or did not have a recorded age. We utilized the area deprivation index (ADI) as a measure of socioeconomic disadvantage, and patients were excluded if they were in a county that did not have a corresponding ADI score (0.3%). ADI scores were calculated by county using the ‘Sociome’ package in R software. Both the 2009 and 2019 county ADI scores were used based on patient diagnosis year. ADI quartiles were then assigned by decade (2000-2009 and 2010-2019). The quartiles were calculated by first identifying the median ADI score for each decade, and then assessing the median of the lower and upper half to determine the lower and upper quartile value. Analyses were also completed by state Medicaid expansion status. Both cause-specific and observed survival (OS) were calculated by five-year periods from 2005 to 2019. The net survival time was assessed at 12 to 60 months in 12-month increments for 2005-2014 with only an upper limit of 48 months survival able to be calculated for patients diagnosed between 2015-2019. The Kaplan-Meier Method was used for all survival calculations.

Results:

A total of 4,382 patients were found to meet criteria for inclusion. Specific characteristics of the analyzed population are listed in Table 1. OS for the entire group was 60.6% at 60 months (95% CI 58.9%-62.3%), with a cause-specific survival at 60 months of 64.3% (95% CI 62.7%-65.9%). For AYA ALL patients diagnosed from 2005 to 2009, cause-specific survival for the ADI quartiles diverged over time and at 48 months was significantly higher in patients residing in a county with an ADI value of 1 (least disadvantaged) than in those residing in a county with an ADI value of 4 (most disadvantaged) [66.6%, 95% CI 62.5-70.4% versus 51.2%, 95% CI 40.2-61.2% p<0.05], although this difference was not significant at 60 months. This difference was also seen in OS at 48 months and persisted at 60 months [62.0%, 95% CI 57.9-65.8% versus 45.7%, 95% CI 35.3-55.5% (48 mo.) and 59.7%, 95% CI 55.6-63.5% versus 45.7%, 95% CI 35.3-55.5% (60 mo.) p<0.05]. There was no significant difference in cause-specific or OS by ADI quartile for patients diagnosed from 2010-2014. However, this difference in survival reoccurred in the most recent data available (Figure 1). For AYA ALL patients diagnosed from 2015 to 2019, cause-specific survival at 36 and 48 months was significantly higher in patients residing in a county with an ADI value of 1 than in those residing in a county with an ADI value of 4 [79.7%, 95% CI 75.6-83.2% versus 65.8%, 95% CI 55.8-74.0% (36 mo.) and 78.6%, 95% CI 74.2-82.3% versus 62.4%, 95% CI 51.8-71.3% (48 mo.) all p<0.05]. This difference was also seen in OS for all survival intervals from 12 to 48 months [90.2%, 95% CI 87.6-92.3% versus 81.3%, 95% CI 74.4-86.5% (12 mo.); 82.9%, 95% CI 79.4-85.8% versus 72.9%, 95% CI 64.9-79.3% (24 mo.); 77.1%, 95% CI 72.9-80.7% versus 62.1%, 95% CI 52.4-70.3% (36 mo.); and 76.0%, 95% CI 71.6-79.8% versus 58.8%, 95% CI 48.6-67.7% (48 mo.) all p<0.05]. There were no statistically significant differences noted in cause-specific and observed survival between states that expanded Medicaid versus those that did not.

Conclusions:

Socioeconomic disadvantage was associated with significantly worse long-term survival in AYA patients with ALL. This gap reappears over time despite both treatment innovations and public policy changes. Urgent interventional approaches are needed to target this highly vulnerable population.