Introduction: Pneumonia is a prevalent and serious complication in acute myeloid leukemia (AML), affecting more than 25% of treated patients and substantially contributing to adverse clinical outcomes. The hypothesis posits that AML-associated pneumonia mortality demonstrates significant socioeconomic and regional disparities across the U.S. population.

Objective: To examine mortality trends in AML-associated pneumonia among U.S. adults aged ≥65 from 1999 to 2023 and project rates through 2050, focusing on socioeconomic disparities.

Methods: Mortality data from the CDC WONDER “Multiple Cause of Mortality” dataset (1999–2023) were analyzed using ICD-10 codes for pneumonia (18) and AML (C92). Age-adjusted mortality rates (AAMR) per million were standardized to the 2000 U.S. population. Joinpoint regression estimated annual percent change (APC) with 95% CI, using a significance threshold of p < 0.05. Trends were forecasted using ARIMA after ADF-based stationarity testing.

Results: A total of 12,447 AML-associated pneumonia deaths were recorded. AAMR rose to 13.7 per million (95% CI: 12.7–14.7) in 2020. The ARIMA model, with AIC 33.41 and RMSE 1.05, projected AAMR of 11.6 in 2030 (CI: 8.73–14.47), 2040 (CI: 7.13–16.07), and 2050 (CI: 5.97–17.23). Males consistently exhibited higher AAMR, reaching 16.15 in 2050 (CI: 14.87–17.43), compared to females at 7.9 (CI: -0.69–16.49). Historically, males exhibited higher AAMR (peak: 19.9, 95% CI: 18.1–21.7) than females (9.6, 95% CI: 8.5–10.7). A significant increase was noted among non-Hispanic Whites (APC: 0.57%, 95% CI: 0.27–0.91; p < 0.001). The Western region reported the highest AAMR, maintaining 12.9 per million from 1999 to 2023. Large Central Metro areas peaked at 14.9 per million (95% CI: 12.9–17.0) in 2020. California had the highest state-level AAMR (14.5, 95% CI: 13.7–15.2).Conclusion: Mortality from AML-associated pneumonia increased from 1999 to 2023, peaking post-COVID. Significant disparities were observed among males, non-Hispanic Whites, residents of the West, large metropolitan areas, and California, indicating the necessity for targeted interventions in response to projected rising trends.

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