Poorer Relapse-Free Survival in Hispanic Children Diagnosed with Acute Myeloid Leukemia Compared with Non-Hispanics: A Texas Single Institution Experience

Introduction: Acute myeloid leukemia (AML) comprises about 18% of childhood leukemias, with an incidence of 7.7 cases per million in the United States. The evidence for variation in disease distribution by race and ethnicity is limited, although there is a slight increased risk for the promyelocytic subtype in Hispanics (Puumala et al, Pediatr Blood Cancer, 2014). In earlier treatment eras (pre-2002), the Children's Cancer Group reported Hispanics with AML to have inferior overall survival (OS) when compared with non-Hispanics (Lange et al, Blood, 2008; Aplenc et al, Blood, 2006), but their event-free survival did not differ significantly. According to recent SEER data, both Hispanic children and adults with AML demonstrated similar OS disparities (Hossain et al, Cancer Epidemiol, 2015; Patel et al, Am J of Clin Oncol, 2015), despite the fact that age at presentation and cytogenetic features were more favorable in Hispanics compared with non-Hispanics. In order to better understand the impact of Hispanic ethnicity upon AML outcomes, we examined relapse-free survival (RFS) and OS in children diagnosed with AML at Texas Children's Hospital (TCH), which has a large Hispanic population, and compared host, disease, and treatment factors that may have affected outcomes.

Methods: We retrospectively reviewed medical records from children (age 0-21 years) with newly diagnosed AML treated at TCH between 1998 and 2015. Subjects with acute promyelocytic leukemia or therapy-related AML were excluded. Self-reported race and ethnicity were used to categorize the study population into Hispanics (of any race) and non-Hispanics. Differences in proportions of host, disease, and treatment characteristics between the two groups were compared using Pearson's X² test. The Kaplan-Meier method was applied to estimate RFS and OS. We then used the Wilcoxon-Breslow-Gehan test to determine if survival functions (RFS and OS) were statistically different by ethnicity, adjusting for treatment era (pre- vs, post 2002). RFS was defined as time from the date of diagnosis until date of relapse. Patients without an event were censored at the date of last known contact. Research was performed under a local Institutional Review Board-approved protocol and in accord with the Declaration of Helsinki.

Results: Of the 99 AML cases with available clinical information, 37 (37%) self-identified as Hispanic. Host, disease, and treatment factors in Hispanic and non-Hispanic subjects with AML did not differ according to prognostic factors such as age at diagnosis or favorable cytogenetic features (Table 1). Additionally, Hispanics and non-Hispanics did not differ significantly in cause of death (disease-related or other). The groups did not differ significantly in OS, but Hispanics had significantly poorer RFS (p=0.03) (Figure 1).

Conclusions: Despite no significant differences in frequency of known AML risk factors, the TCH Hispanic population was both significantly more likely to relapse and had an earlier time to relapse than did non-Hispanics. This effect was even more surprising given that this population was twice as likely to have AML characterized by favorable cytogenetic features, although this enrichment did not reach significance. Of note, the RFS difference we observed is unlikely to be related to treatment compliance or socioeconomic factors, as all AML patients were hospitalized throughout treatment. Further study is needed to confirm this finding in a larger pediatric AML cohort, and to identify host factors related to Hispanic ancestry that may be responsible for the differences observed in RFS.

Table 1: Patient characteristics

*Number of subjects in each category is shown in parentheses unless otherwise specified.

SD=Standard deviation, CBF = core binding factor, MRD = minimal residual disease, BMT = bone marrow transplant

Figure 1: Comparison of AML relapse-free survival in Hispanics vs. non-Hispanics, adjusted for treatment era