Acute myeloid leukemia (AML) is a heterogeneous and aggressive hematologic malignancy with a particularly poor prognosis in older adults. Over the past two decades, treatment options have expanded significantly with the introduction of hypomethylating agents and targeted therapies, but the population-level effects of these innovations on survival remain incompletely understood. We conducted a retrospective cohort analysis using the SEER 17 database, studying AML cases diagnosed from 2000 to 2022. Patients were stratified into five age groups; 0–14, 15–39, 40–64, 65–74, and 75+ years, and the study period was divided into four therapeutic eras: 2000–2005, pre-modern therapies, 2006–2010, early treatment changes, 2011–2015, hypomethylating agent era, and 2016–2022, targeted therapy era. For each group and era, we calculated incidence and estimated observed and relative survival at 12, 24, 36, 48, and 60 months. AML incidence remained highest in older adults across the entire study period, with little variation over time. Relative 5-year survival improved in all age groups, though gains were uneven. The pediatric group (0–14 years) saw an increase from 62.2% to 69.1%, and the 15–39 age group improved from 50.6% to 66.1%. The 40–64 group increased from 27.9% to 44.4%, while adults aged 65–74 experienced a survial rise from 9.3% to 19.6%. The oldest group (75+) showed small survival improvement, from 1.9% to 4.7%. While the most dramatic improvements were observed in patients under 40, there were modest but notable gains among adults aged 65 and older, especially during the targeted therapy era. These trends reflect a combination of more effective frontline regimens, better supportive care, and greater access to molecular diagnostics and novel agents. However, outcomes for older patients remain poor, likely due to age-related comorbidities, reduced treatment tolerance, and underrepresentation in clinical trials. Our findings highlight both progress and ongoing disparities in AML care. Despite meaningful survival improvements since 2000, especially among younger and middle-aged adults, elderly patients continue to face disproportionately poor outcomes. This underscores the need for age-adapted therapeutic strategies and further innovation in treating geriatric AML. In an era of personalized medicine, expanding access to less toxic therapies and improving inclusion of older adults in clinical research will be essential to closing the survival gap.

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2025
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