Distance to Treatment Center Is Associated With Survival in Children and Young Adults With Acute Lymphoblastic Leukemia

By Seth Rotz, MD

Outcomes in pediatric patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) have improved in more recent eras. Advancements in disease-directed therapy as well as supportive care have decreased the rate of relapse and treatment-related mortality.1 Yet, despite improvements in treatment for children and adolescent and young adults (AYAs; age range 15-39 years) with acute leukemia, certain socioeconomic or health services issues may affect outcomes.

Variables linked to a higher risk of mortality in children with acute leukemia

Children with acute leukemia (AML and ALL) have a higher risk of death if they are of a lower socioeconomic status.2 Treatment facility type, insurance status and race may also play a role in outcomes.3-7 However, little has been explored regarding distance from cancer treatment center and outcomes in acute leukemia.

Does distance to treatment center affect outcomes in acute leukemia?

We hypothesized that distance to treatment center affects outcomes of children and young adults with acute leukemia because a longer distance might strain families and caregivers to a greater degree and might lead to delays in seeking care both at diagnosis and for complications during treatment.8

To test our hypothesis, we queried the National Cancer Database and developed models to predict the contribution of distance to treatment center to overall survival for children and AYAs with AML and ALL. In our analysis, we included patients 39 years old or younger who were diagnosed with AML or ALL between 2004 and 2015.

Distance to the treatment center was determined by measuring the cancer center’s address to the center of the zip code of the patient’s address and was categorized as: < 10 miles, > 10-≤ 20 miles, > 20-≤ 50 and > 50 miles. Other factors that were analyzed included Carleson-Deyo comorbidity score, sex, race/ ethnicity, insurance status, community median income, year of diagnosis, age, and rural vs. urban zip code. Models of overall survival were stratified based on the type of leukemia.

Key findings

In total, 12,301 patients with AML and 22,683 patients with ALL were analyzed (Figure 1).

The final ALL model included distance to treatment center, Charlson-Deyo score, age, race, insurance status, and community income level. Compared with distances > 50 miles, all other distances were associated with improved survival (hazard ratio [HR] for ≤10 miles, 0.91; P = .04; HR for > 10 to ≤ 20 miles, 0.86; P = .004; HR for > 20 to ≤ 50 miles, 0.87; P = .005). The final model for AML included the same variables as the ALL model, except for distance to treatment center, which was not statistically significant.

Interestingly, for patients with ALL, the distance to treatment center remained significant after adjustments for other socioeconomic factors such as community income and insurance status. Furthermore, rural and urban zip codes were not statistically significantly different in this study. Taken together, these data suggest that the physical distance to the treatment center, as opposed to only the intrinsic community factors, influences overall survival for ALL patients.

Differences in ALL and AML survival rates and distance to treatment may be tied to treatment approach

The association between a distance to treatment center > 50 miles and poorer overall survival for both children and young adults with ALL—but not AML—is intriguing. Unfortunately, data from the NCDB do not discern between treatment-related and disease-related mortality, although, it is plausible that the difference in overall treatment approaches for ALL and AML may be responsible.

The typical treatment for ALL is delivered mostly on an outpatient basis and extends for multiple years. ALL treatment requires patients to take many trips to the treating center for therapy and intermittent complications (infections, dehydration, etc.). Conversely, AML treatment is typically given almost exclusively on an inpatient basis and lasts for months rather than years.

Increased attention to the treatment challenges of acute lymphoblastic leukemia is warranted

We surmise that potential challenges for patients with ALL related to traveling to appointments and leading to delays in therapy or difficulty in getting to the treatment center for emergent complications might be responsible for the differences observed in this study. We conclude that increased attention to adherence, supportive care and logistics for patients with ALL traveling long distances is warranted.

References

1. Alexander TB, Wang L, Inaba H, et al. Decreased relapsed rate and treatment-related mortality contribute to improved outcomes for pediatric acute myeloid leukemia in successive clinical trials. Cancer. Oct 1 2017;123(19):3791-3798. doi:10.1002/cncr.30791
2. Petridou ET, Sergentanis TN, Perlepe C, et al. Socioeconomic disparities in survival from childhood leukemia in the United States and globally: a meta-analysis. Ann Oncol. Mar 2015;26(3):589-97. doi:10.1093/annonc/mdu572
3. Wolfson J, Sun CL, Wyatt L, Stock W, Bhatia S. Adolescents and young adults with acute lymphoblastic leukemia and acute myeloid leukemia: impact of care at specialized cancer centers on survival outcome. Cancer Epidemiol Biomarkers Prev. Mar 2017;26(3):312-320. doi:10.1158/1055-9965.EPI-16-0722
4. Borate UM, Mineishi S, Costa LJ. Nonbiological factors affecting survival in younger patients with acute myeloid leukemia. Cancer. Nov 1 2015;121(21):3877-84. doi:10.1002/cncr.29436
5. Seif AE, Fisher BT, Li Y, et al. Patient and hospital factors associated with induction mortality in acute lymphoblastic leukemia. Pediatr Blood Cancer. May 2014;61(5):846-52. doi:10.1002/pbc.24855
6. Aplenc R, Alonzo TA, Gerbing RB, et al. Ethnicity and survival in childhood acute myeloid leukemia: a report from the Children’s Oncology Group. Blood. Jul 1 2006;108(1):74-80. doi:10.1182/blood-2005-10-4004
7. Kadan-Lottick NS, Ness KK, Bhatia S, Gurney JG. Survival variability by race and ethnicity in childhood acute lymphoblastic leukemia. JAMA. Oct 15 2003;290(15):2008-14. doi:10.1001/jama.290.15.2008
8. Rotz SJ, Wei W, Thomas SM, Hanna R. Distance to treatment center is associated with survival in children and young adults with acute lymphoblastic leukemia. Cancer. Dec 15 2020;126(24):5319-5327. doi:10.1002/cncr.33175

About the author: Dr. Rotz is Assistant Professor of Pediatrics, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University.