A recent study published in Blood Advances showed that cytogenic lesions in children with acute myeloid leukemia (AML) differ by race-ethnicity, with higher rates of specific poor prognosis lesions among Black patients. Black and Hispanic pediatric patients with AML also face worse outcomes compared to their white counterparts, regardless of genetic disease features, according to researchers led by Shannon E. Conneely, MD, of Baylor College of Medicine in Houston, Texas.
To identify differences in cytogenetic features, disease phenotype, and survival among children with AML of various racial-ethnic backgrounds, Dr. Conneely and colleagues conducted a retrospective study using data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) AML database. The researchers analyzed prospective data from patients with de novo AML enrolled in three pediatric AML clinical trials, including age, sex, self-reported race and ethnicity, primary cytogenetic lesion, presence or absence of specific recurrent mutations, clinical features at presentation, clinical response, treatment protocol, use of gemtuzumab ozogamicin (GO), and survival time.
A total of 843 patients were included in the study, from the following racial-ethnic backgrounds:
- white non-Hispanic (n=552)
- Hispanic (n=154)
- Black non-Hispanic (n=108)
Patients’ median age at diagnosis was 10.1 years (range = 3.3-14.7), and median time under observation was 4.5 years (range = 1.4-6.0). Cytogenetic data was not provided for 4.7% of patients (n=38).
Dr. Conneely and colleagues found that Black patients were twice as likely to have high-risk genetic features compared with non-Black patients, and were more than five times as likely to have the specific KMT2Ar rearrangement t(6;11)(q27;q23) associated with lower event-free survival (EFS; hazard ratio [HR] = 2.48; 95% CI 1.4-4.4) and overall survival (OS; HR=2.89; 95% CI 1.54-5.44).
“Outcome disparities by race-ethnicity were evident even among cytogenetic subgroups typically associated with favorable prognosis,” the authors wrote. While Black patients were more likely to have t(8;21) AML associated with better outcomes, the three-year OS rate among Black patients with t(8;21) was 61% compared with 87% for White non-Hispanic patients. OS among Black patients with core binding factor (CBF) AML was 61% – equivalent to the OS rate of patients in the cohort without this favorable cytogenetic subtype.
Among Black and Hispanic patients, poor prognosis lesions were associated with worse than expected outcomes, “suggesting potentially additive negative effect of race-ethnicity on survival among these subsets,” the authors wrote. The EFS rates among Black and Hispanic patients with KMT2Ar AML were 14% and 29%, respectively, compared with 47% for White non-Hispanic patients.
No significant difference in white blood cell count at diagnosis was found in this cohort overall or within the specific cytogenetic groups.
Events contributing to poor survival outcomes also differed by race-ethnicity. While Hispanic patients with KMT2Ar AML were more likely to experience induction failure, all Black patients in the cohort were more likely to die within 50 days of treatment initiation compared with patients of other racial-ethnic backgrounds. Hazard ratios for three-year survival outcomes by race-ethnicity for patients in select cytogenetic subgroups in the TARGET cohort are shown in the TABLE.
In this study, Black patients were less likely to undergo hematopoietic cell transplantation than White non-Hispanic patients, suggesting that “a relative lack of stem cell transplant donors may contribute to poor outcomes in minority patients,” according to the authors. However, they noted, the TARGET AML data is insufficient to confirm whether a lack of donors contributes to fewer transplants or outcome disparities.
“Every aspect of clinical care … should be rigorously studied from the perspective of the racial-ethnic outcome disparities described in this and similar studies.”
—Shannon E. Conneely, MD
The researchers also found that Black patients with CBF AML in this study experienced EFS benefit from the addition of GO (HR=0.30; 95% CI 0.10-0.92) compared with White non-Hispanic or Hispanic patients. This suggests “biologic differences may exist which influence GO responsiveness within certain AML subtypes, or that other factors contributing to care of patients receiving an investigational agent may be at play,” the authors wrote.
“Potential causes of these disparities begin at the level of the patient and the biologic features of their leukemia, expand outwards to the healthcare systems in which they are treated, and reach ultimately into the society in which they live,” Dr. Conneely wrote. “We should continue to study the epidemiology of high-risk AML cytogenetics, epigenetics, and pharmacogenomics of AML therapy as potential causes of racial-ethnic disparities in childhood AML.”
However, Dr. Conneely added, “we must also systematically test the hypothesis that structural inequities disproportionately affecting racial-ethnic minorities contribute to these outcome disparities. Every aspect of clinical care – from that received before and leading up to diagnosis, during inpatient and outpatient therapy, and through to surveillance in long-term survivorships – should be rigorously studied from the perspective of the racial-ethnic outcome disparities described in this and similar studies.”
Conneely SE, McAtee CL, Gupta R, et al. Association of race and ethnicity with clinical phenotype, genetics, and survival in pediatric acute myeloid leukemia [published online ahead of print, 2021 Oct 7]. Blood Adv. doi: 10.1182/bloodadvances.2021004735.