Background: Adolescents and young adults (AYAs), defined as individuals aged 15–39, represent a unique group in hematology, often transitioning between pediatric and adult care systems. Acute lymphoblastic leukemia (ALL) is one of the more common hematologic malignancies in this age range. Despite advances in treatment, AYAs with ALL experience poorer outcomes compared to younger patients, partly due to delayed diagnosis, limited clinical trial participation, and inconsistent treatment protocols between pediatric and adult age ranges. While survival rates for AYAs with cancer have overall improved, ALL remains a challenge due to the transition of care gaps in this underserved population. This study aims to assess outcome disparities specific to the AYA population with ALL.

Methods: This retrospective cohort study analyzed data from 17 registries from Surveillance, Epidemiology, and End Results SEER Research Plus database from 2000-2022, including AYA's (aged 15-39) diagnosed with primary ALL between 2000 and 2017 to allow at least 5 years of follow-up for each participant. The primary outcome was five-year overall survival, defined as being alive at least five years from the initial diagnosis. Analyzed covariates included age, sex, race/ethnicity, median household income, ALL subtype, treatment (chemotherapy and radiation), and development of secondary malignancies. Bi-phenotypic leukemias were excluded from the analysis. Univariate and multivariable logistic regression models were used to evaluate associations between covariates and five-year survival, reported as adjusted odds ratios (aOR) with 95% confidence intervals (CIs).

Results: Between 2000-2017, a total of 4,842 AYA patients were diagnosed with ALL with a minimum of five years follow-up for each patient. Individuals aged 15-19 comprised the largest share of the population at 37.3%, followed by those aged 20-24, who represented 19.7%. The remaining age groups: 25-29, 30-34, and 35-39 showed similar distributions, making up 15.0%, 14.1%, and 13.9% of the cohort, respectively. Median age at diagnosis was 22 years (IQR 18-31), with 63.7% male and 36.3% female. Hispanic individuals represented the largest racial/ethnic group in the study, comprising 45.2% of the total population. Non-Hispanic White (NHW) patients followed at 39.0%, while non-Hispanic Black (NHB), Non Hispanic Asian/Pacific Islander, and Other made up fewer proportions at 6.5%, 8.0%, and 1.3%, respectively. Nearly all patients (95.8%) received chemotherapy, and the majority had B-ALL (87.2%) with T-ALL being a minority (12.8%). Of these, 3.6% developed a secondary malignancy during follow up.

The median (IQR) overall survival in this cohort was 5.8 (1.4-12.1) years. Outcomes were stratified based on five-year survival status, with 54.5% of patients surviving beyond five years (n=2,641) and 45.5% surviving less than five years since diagnosis (n=2,201).

Cause of death was primarily cancer-specific among those who died within five years (81.4%), whereas, among longer-term survivors, only 6.5% experienced cancer related mortality, with a majority remaining alive at the time of analysis (p<0.001). Of those who survived >5 years, 4.9% died with a median survival of 7.5 years.

In univariate analyses, age, race/ethnicity, chemotherapy, and radiation were significantly associated with five-year survival (p<0.001), while gender and income were not significant predictors (p =0.4 and p = 0.16, respectively). In a multivariate analysis, age was a significant predictor and patients aged 35-39 years had lower odds of 5-year survival compared to the 15-19 year group (aOR 0.27, 95%CI 0.22–0.32, p<0.001). Non-Hispanic Black patients had 45% lower odds of survival (aOR 0.55, 95%CI 0.42–0.71, p<0.001), and Hispanic patients had 47% lower odds (aOR 0.53, 95% CI 0.48–0.61, p <0.001) compared to non-Hispanic whites (reference group). Chemotherapy doubled the odds of survival (aOR 2.04, 95%CI 1.49–2.78, p<0.001), and radiation therapy increased the survival odds by 48% (aOR 1.48, 95% CI 1.28–1.71, p<0.001).

Conclusion: In this cohort of AYA patients with ALL, oldest age at diagnosis and racial/ethnic minorities were associated with significantly lower risk-adjusted odds of five-year overall survival. These findings highlight persistent disparities in AYA ALL outcomes and emphasize the need for targeted efforts to address age- and race-based inequities in survivorship.

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2025
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