Survival outcomes in therapy-related acute lymphoblastic leukemia: A population-based analysis from SEER (2000–2022)

Abstract

Abstract Background Therapy-related acute lymphoblastic leukemia (t-ALL) is a rare and poorly characterized entity typically arising after cytotoxic treatment for a prior malignancy. Data on clinical characteristics and survival outcomes in t-ALL remain limited due to its rarity. We utilized the SEER 17 registries to describe the demographics and survival predictors in patients with presumed therapy-related ALL. Methods We extracted data from the SEER 17 Incidence database (2000–2022) including patients with ALL histologies (ICD-O-3: 9811–9817, 9835–9837) whose diagnosis occurred as a second or later primary malignancy (defined by sequence number ≥2). Variables included age, sex, race, ethnicity, year of diagnosis, and survival outcomes. Patients were grouped into three age categories: <40 (AYA), 40–59, and ≥60 years. Overall survival (OS) was assessed using Kaplan-Meier methods, and Cox proportional hazards regression was used to evaluate predictors of mortality. Results A total of 2,317 patients with presumed therapy-related ALL were identified. The median age at diagnosis was 61.3 years. The cohort was balanced by sex (50.1% male and 49.9% female). The majority of patients were White (83.3%), followed by Black (8.1%), Asian or Pacific Islander (7.7%), and American Indian/Alaska Native (0.7%). Hispanic ethnicity was present in 18.9% of patients. Age distribution showed that 13.1% were adolescents and young adults (AYA, age <40), 24.4% were aged 40–59 years, and 62.5% were aged 60 years or older. Survival analysis included 1,986 patients with complete survival data, among whom 1,346 deaths were observed over a total follow-up time of 65,057 person-months. Kaplan-Meier curves demonstrated decreasing survival with increasing age. In Cox proportional hazards models, age was a significant predictor of mortality. Compared to AYA patients, those aged 40–59 had a hazard ratio (HR) of 1.53 (95% CI: 1.25–1.89, p<0.001), and those aged 60 or older had an HR of 2.94 (95% CI: 2.43–3.56, p<0.001). Sex was not significantly associated with survival (HR 1.00, 95% CI: 0.90–1.11, p=0.99), and neither race nor ethnicity showed significant independent associations with outcomes. Conclusions This is the largest population-based study to date describing therapy-related ALL. t-ALL predominantly affects older adults and carries a poor prognosis. Age is a strong predictor of mortality, while sex, race, and ethnicity were not independently associated with outcomes. These findings highlight the need for age-adapted treatment strategies and may support the inclusion of t-ALL as a distinct high-risk subgroup in clinical trials.