Race and ethnicity

ALL subtype. The reason for better outcomes in White and Asian children than in Black and Hispanic children is at least partially explained by the different spectrum of ALL subtypes. For example, Black children have a higher relative incidence of T-ALL, lower rates of favorable genetic subtypes of B-ALL, and higher rates of the TFC3::PBX1 (t(1;19)) translocation. Hispanic and Latino children have a lower prevalence of the favorable ETV6::RUNX1 fusion gene.[90] Hispanic and Latino children have a higher frequency of CRLF2 rearrangements and IKZF1 deletions.[90-92] They also have a higher frequency of the IKZF1PLUS profile (IKZF1 deletion plus deletion of CDKN2A, CDKN2B, PAX5, or PAR1 [in the absence of ERG deletion]).[90]

Treatment adherence. Differences in outcome may also be related to treatment adherence, as illustrated by a study of adherence to oral mercaptopurine (6-MP) in maintenance therapy. In the first report from the study, there was an increased risk of relapse in Hispanic children compared with non-Hispanic White children, depending on the level of adherence, even when adjusting for other known variables. However, even with adherence rates of 90% or more, Hispanic children continued to demonstrate increased rates of relapse.[93] In the second report from the study, adherence rates were shown to be significantly lower in Asian American and African American patients than in non-Hispanic White patients. A greater percentage of patients in these ethnic groups had adherence rates of less than 90%, which was associated with a 3.9-fold increased risk of relapse.[94]

Ancestry-related genomic variations. Ancestry-related genomic variations may also contribute to racial and ethnic disparities in both the incidence and outcome of ALL.[95] For example, the differential presence of specific host polymorphisms in different racial and ethnic groups may contribute to outcome disparities, as illustrated by the occurrence of single nucleotide polymorphisms in the ARID5B gene that occur more frequently among Hispanic patients and are linked to both ALL susceptibility and to relapse hazard.[96] In a genome-wide association study (GWAS), the GATA3 variant, rs3824662, was associated with an increased risk of developing BCR::ABL1-like (Ph-like) ALL. Patients with this variant were at increased risk of high minimal residual disease (MRD) at end-induction and at greater risk of relapse. The rs3824662 risk allele is associated with Native American genetic ancestry. The risk allele frequency was 52% in Guatemalan patients, 40% in U.S. Hispanic patients, and 14% in patients of European descent.[97]