Trends in Acute Myeloid Leukemia mortality among patients with myelodysplastic syndrome in the United States (1999–2024): A CDC wonder database analysis

Abstract INTRODUCTION: Myelodysplastic syndromes (MDS) are known precursors to acute myeloid leukemia (AML), especially in older adults, where disease progression significantly contributes to mortality. However, nationwide mortality trends in AML patients with underlying MDS remain understudied. This study investigates AML-related mortality trends in the context of MDS from 1999 to 2024 in the United States. METHODS: We conducted a retrospective analysis using the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database. Death certificates from 1999 to 2024 of adults aged ≥65 listing AML as the underlying cause and MDS as a contributing cause were analyzed. Age-adjusted mortality rates (AAMRs) per 1000,000 population and annual percent change (APC) were calculated using Joinpoint regression. RESULTS: A total of 16,963 deaths were reported due to AML with MDS as a contributing condition. While AAMR slightly declined from 13.7 (1999) to 13.0 (2024), a notable increase was observed from 1999 to 2009 (APC: 3.17). Males exhibited a higher AAMR (22.9) compared to females (10.0). Non-Hispanic Whites (16.3) had the highest AAMR among all racial/ethnic groups. AAMRs were higher in metropolitan (15.9) than non-metropolitan (15.0) areas. Regionally, the Midwest recorded the highest AAMR at 17.9. CONCLUSION: Our findings highlight the persistent burden of AML mortality in patients with MDS, particularly among males and NH Whites. Targeted interventions are needed to address these disparities and improve outcomes in high-risk populations. Keywords: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Age-Adjusted Mortality Rates; CDC WONDER; Hematologic Malignancies; Racial and Geographic Disparities.