Toward Equity in Access for ALL

Approximately 6,500 individuals are diagnosed with acute lymphoblastic leukemia (ALL) each year in the U.S.,¹  representing just a fraction of ALL cases worldwide. Consistent with U.S. epidemiologic data demonstrating higher rates of ALL among people of Hispanic/Latino ethnicity,²  available literature suggests that the incidence of ALL in low- and middle-income countries (LMIC), particularly across Central America, far exceeds U.S. estimates.^{3, 4}  Over the last decade, we have witnessed a wide array of tremendous breakthroughs in ALL: enhanced genomic classifications, technological advancements in residual disease quantification, expansion of the pediatric approach into adult ALL populations, novel targeted immune-therapeutics, and engineered cellular therapies — the additive effect of which has resulted in improved leukemia-free and overall survival for many patient subgroups. However, these newer approaches are complex and remarkably expensive, and accessibility remains uneven across the U.S. The situation has been far worse for patients with ALL and providers in LMICs, where access to new protocols and therapeutics has until recently been largely elusive.

It is with this backdrop that I posit that recognition of the problem and efforts to improve access to modern ALL care among LMICs is among the Year’s Best of 2023. This year, a report sponsored by the Americas Health Foundation detailed expert recommendations on the diagnosis, treatment, and management of adult ALL in Latin America.⁵  The panel included specialists from Argentina, Brazil, Chile, Colombia, and Mexico, who worked together to delineate best practices adapted to the realities of Latin American countries. The authors identified cost as the single greatest limitation in implementing diagnostic tests and innovative ALL therapies in LMICs. Similarly, in a detailed 2023 report by the Mexico in Alliance with St. Jude (MAS) collaborative, which included data for 2,116 pediatric patients with ALL treated at 16 centers across Mexico, the authors concluded that “outcomes are lower than desirable, with a high frequency of treatment-related toxicity and relapse, and inconsistent access to diagnostic tests, both at diagnosis to characterize ALL samples and for disease monitoring through MRD”.⁶  Based on this work, the MAS group developed consensus guidelines for pediatric ALL care in LMICs; these guidelines are now used in practice in over 10 pediatric cancer centers.⁶ 

This year also saw the publication of a prospective clinical trial aimed at improving outcomes among adolescents and young adults (AYAs) with ALL diagnosed in LMICs.⁷  In Mexico, where ALL is the predominant form of acute leukemia in adults, clinical researchers capitalized on the success of the pediatric regimen administered to AYAs in the U.S. and Europe, conducting a prospective study of the C10403 pediatric-based ALL regimen in AYAs and adults (up to 49 years old) across five centers in Mexico and one center in Guatemala. The investigators substituted agents based on availability (e.g., E. Coli L-asparaginase replaced the more expensive pegaspargase) but otherwise largely followed the original protocol. Among the 95 enrolled patients, the two-year overall and relapse-free survival rates were 72.1% and 68.4%, respectively. Not only were these estimates similar to the original U.S. C10403 study outcomes,⁸  but they were also strikingly superior to historic survival rates among AYA patients with ALL treated at referral centers in Mexico City, where only 26% of patients were reported to be alive at three years following diagnosis.⁹  Importantly, treatment-related deaths occurred in 9% of the study cohort, a rate higher than that seen in the U.S. but a marked improvement relative to historic treatment-related mortality rates in the region.

Equity in access to high-quality therapies and approaches is a pervasive issue that extends far beyond ALL. However, for a relatively rare yet curable disease that is enriched in underrepresented populations and LMICs, the recent spotlight on inequities in ALL is invaluable. Although new technologies and therapeutics are certainly more available in the U.S., recently published studies have also shown that access to ALL specialists,¹⁰  clinical trials,¹¹  and novel therapies¹²  also appears reduced in U.S. Hispanic/Latino ALL populations, suggesting that there is more work to be done to conquer this issue both at home and abroad. As a hematology community, we must continue to raise this issue to prominence and work together towards a future where equal access to hematology care will exist for all — including those with ALL.