Association of race and ethnicity with clinical phenotype, genetics, and survival in pediatric acute myeloid leukemia

Abstract

Black and Hispanic children with acute myeloid leukemia (AML) have worse outcomes compared to White children. AML is a heterogeneous disease with numerous genetic subtypes in which these disparities have not been specifically investigated. In this study, we used the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database to examine the association of race-ethnicity with leukemia cytogenetics, clinical features, and survival outcomes within major cytogenetic subgroups of pediatric AML. Compared to White non-Hispanic patients, t(8;21) AML was more prevalent among Black (OR, 2.22; 95% CI, 1.28-3.74) and Hispanic patients (OR, 1.74; 95% CI, 1.05-2.83). The poor prognosis KMT2A rearrangement t(6;11)(q27;q23) was more prevalent among Black patients (OR, 6.12; 95% CI, 1.81-21.59). Among those with KMT2Ar AML, Black race was associated with inferior event-free survival (EFS) (HR, 2.31; 95% CI, 1.41-3.79) and overall survival (OS) (HR, 2.54; 1.43-4.51). Hispanic patients with KMT2Ar AML also had inferior EFS (HR, 2.20; 95% CI, 1.27-3.80) and OS (HR, 2.07; 95% CI, 1.09-3.93). Similarly, among patients with t(8;21) or inv(16) AML (i.e., core binding factor AML), Black patients had inferior outcomes (EFS HR, 1.93; 95% CI, 1.14-3.28 and OS HR, 3.24; 95% CI, 1.60-6.57). This disparity was not detected among patients receiving gemtuzumab ozogamicin. In conclusion, racial-ethnic disparities in survival outcomes among young people with AML are prominent and vary across cytogenetic subclasses. Future studies should explore the socioeconomic and biologic determinants of these disparities.

Racial and ethnic disparities in acuity of presentation among children with newly diagnosed acute leukemia

“…Importantly, fewer statistically significant differences in presenting laboratory results were detected between Hispanic and non-Hispanic White patients. 9 In contrast to our findings, in a previous study a difference in median WBC was not found between Black and White children. 10 The lack of difference in that study may be due to selection bias caused by using trial-collected biospecimens, which favors children with lower acuity at presentation.…”

“…Previous studies suggest monocytic AML subtypes (including those with KMT2A rearrangements) present more frequently with elevated WBC count 8 . While KMT2A ‐rearranged AML is not broadly associated with Black race, the specific KMT2A ‐rearrangement t(6;11)(q27;q23) that carries a poor prognosis is more common among Black children 9 . In contrast to our findings, in a previous study a difference in median WBC was not found between Black and White children 10 .…”

High early death rates, treatment resistance, and short survival of Black adolescents and young adults with AML

“…Interestingly, a high frequency of t (8;21) in Black patients with AML has also recently been reported in pediatric AML, with 21.3% of Black vs 10.9% of non-Hispanic White patients harboring the t(8;21) translocation. 22 We observed differences in the frequencies of AML-associated mutations, with Black AYA patients harboring more often mutations in the ASXL1 [23][24][25] and BCOR 26-28 genes, which have been reported to confer worse outcomes, and carrying less frequently prognostically favorable NPM1 mutations 26,29 and biallelic mutations in the CEBPA gene. 26,30,31 Although the lower frequency of those 2 favorable risk markers we report herein may be considered as possible contributors to the inferior treatment outcome of Black AYA patients as compared with the outcome of White AYA patients, the previous notion of poor survival specifically of NPM1mutated/FLT3-ITD low/no younger Black patients with AML may instead raise the possibility of differences in the disease biology of favorable risk AML between Black and White patients with AML.…”

Disparities in acute myeloid leukemia treatments and outcomes

“…Interestingly, this increased frequency seems to be especially pronounced in adolescent and young adult (AYA, aged 18–39 years) AML patients, in whom CBF-AML accounts for 37% of Black AML patients, compared to 22% of White patients in the same age group: in young Black patients t(8;21) accounted for 59% of CBF-AMLs, compared to 46% in White patients [36 ▪ ]. This predominance of t(8;21) was also seen in pediatric Black AML patients, in whom t(8;21) was twice as frequent compared to non-Hispanic Whites [37]. In contrast, 40% of young White AML patients present with cytogenetically normal karyotype at diagnosis, whereas only 19% of Black AYA AML patients have normal chromosomes.…”