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Page 225 Xu et al. J Transl Genet Genom 2021;5:218-39 https://dx.doi.org/10.20517/jtgg.2021.20

[88]
Hispanic/Latino males [71.8% (95%CI: 70.3%-73.3%)] diagnosed back in 1995-2003 ; Black females
diagnosed in 2004-2012 [76.9% (95%CI: 75.2%-78.4%)] had a worse survival rate compared to NHW females
[88]
diagnosed in 1995-2003 [83.9% (95%CI: 83.2%-84.2%)] .

Older adults
Older adult ALL patients have the worst survival across all age groups [77-82] . While approximately 22.5% of
patients are diagnosed after the age of 55 years, 54.6% of ALL-related deaths occur in patients in this age
stratum . This is likely related to the elevated prevalence of multiple high-risk subtypes of ALL in older
[111]
adults. First, both Ph+ ALL and Ph-like ALL are very common subtypes of B-ALL among older adults aged
60 years or above (Ph+ ALL: approximately 50%; Ph-like ALL: 24%-26%) [96-99,112,113] . In addition, older adults
with Ph-negative B-ALL tend to present with high-risk cytogenetics and complex karyotypes [114,115]
associated with increased risks of treatment failure and treatment complications .
[81]

Promisingly, the 1973-2008 SEER data revealed a significant improvement for patients aged over 45 years in
survival among the overall population, NHWs, and in particular APIs (19.8%), and a large but marginally
[89]
significant improvement for Blacks (11.3%) . However, these improvements were not seen in
Hispanic/Latino patients. For instance, in 2003 to 2008, the 5-year survival rate of older adult
Hispanic/Latino ALL patients was only 13.9% compared with 23.6% in NHWs and 17.1% in Blacks ,
[89]
[99]
perhaps due to the high frequency of Ph-like ALL in Hispanic/Latino ALL patients . Similarly, in the 1980-
2011 SEER data, there was a modest improvement of median overall survival rate of ALL among adults aged
60 years or above , partly attributable to advances in novel therapies for Ph+ ALL .
[117]
[116]
FACTORS ASSOCIATED WITH DISPARITIES IN ALL RISK AND OUTCOMES
Differences in ALL tumor biology
Immunophenotype
The World Health Organization (WHO) classifies ALL based first on immunophenotype, and categorizes
patients into either B-ALL or T-ALL , with both comprising multiple subtypes defined by structural
[118]
chromosomal alterations . B-ALL prevalence is higher than T-ALL, accounting for approximately 80% of
[119]
ALL cases in children and 75% in adults in the United States . In childhood ALL, the B-cell
[120]
immunophenotype confers more favorable survival than T-ALL, whereas in adults survival is substantially
higher for T-ALL than B-ALL [5,114,121,122] , likely due to differences in molecular subtypes across age groups. In
both children and adults, B-ALL appears to have a higher incidence in Hispanics/Latinos compared to other
[5]
races/ethnicities . On the other hand, T-ALL occurs more frequently in Black children, in whom a T-ALL-
related genetic variant in USP7 is overrepresented . Thus, the contribution of immunophenotype to
[30]
disparities in the survival of ALL patients may vary across population groups.

Cytogenetic subtypes
The most common chromosomal alterations in childhood B-ALL are high hyperdiploidy (chromosomal
number 51-67) and t(12;21)(p13;q22) translocation encoding the ETV6-RUNX1 fusion gene [115,123] . Each
presents in 25%-30% of children with ALL , and is associated with a favorable prognosis [115,124] . However,
[119]
[119]
both subtypes are less common in adolescent ALL patients and very rare in adult ALL patients . Among
ALL cases in the California Childhood Leukemia Study, the prevalence of high hyperdiploidy was similar in
Hispanics/Latinos and NHWs, at 28.3% and 27.6%, respectively , whereas there was a significantly lower
[125]
frequency of ETV6-RUNX1 translocation in Hispanics/Latinos (13%) than in NHWs (24%) . To our
[126]
knowledge, the frequencies of these two subtypes have not been compared across race/ethnicity in AYAs or
older adults, perhaps due to small numbers.