Introduction: Leukemias, lymphomas, and multiple myeloma are among the hematologic malignancies that pose a significant health burden both internationally and domestically in the United States. These cancers have a high rate of death and morbidity due to their aggressive clinical course and the intensity of the treatments they necessitate. A patient's risk of infection is increased by immunosuppression caused by the cancer and its treatment. Sepsis is one of the most common causes of complications, extended hospital stays, and fatalities among these. This study examines mortality trends between 1999 and 2023 for adults in the United States who had hematologic malignancies and those who had hematologic malignancies with sepsis.

Methodology: Data were retrieved from the CDC WONDER database for the years 1999 to 2023, including individuals aged ≥65 years. Firstly we evaluated mortality trends among people diagnosed with hematologic malignancies(C81-C96) and hematologic malignancies with sepsis(A41) individually. Then, we conducted a head-to-head analysis to determine differences between both groups. We assessed age-adjusted mortality rates (AAMRs) per 100,000 population as stratified by age, sex, race, Hispanic origin, U.S. Census regions, and 2013 urbanization categories. Joinpoint regression (JPR) was used to estimate Annual Percent Changes (APCs) and corresponding 95% confidence intervals (CIs), with statistical significance determined via Monte Carlo permutation test (p < 0.05).

Results: Between 1999 and 2023, there were 1,133,287 deaths due to hematological malignancies and 92,409 deaths where hematological malignancies co-occurred with sepsis. The overall age-adjusted mortality rate (AAMR) was higher for hematological malignancies (124.2) than for those with sepsis (10.3), though both declined significantly (AAPC: -1.05; 95% CI: -1.36 to -0.75, p < 0.000001 and AAPC: -0.45; 95% CI: -0.61 to -0.29, p < 0.000006, respectively). The highest AAMRs were recorded in 2000 (142.66 and 11.0).Males had nearly double the AAMR compared to females in both groups (166 vs 95.21 and 14.03 vs 7.3). Among males with hematological malignancies, mortality declined modestly from 1999 to 2018 (APC: -1.26, p < 0.000001), with a similar trend in females (APC: -1.68, p < 0.000001). Non-Hispanic White individuals had a higher AAMR (128.14) with a declining trend (AAPC: -0.94; 95% CI: -1.26 to -0.61, p < 0.000001). Non-Hispanic Black individuals with sepsis had the highest AAMR (12.22) and also showed a decline (AAPC: -0.96; 95% CI: -1.25 to -0.67, p < 0.000001). Hispanic/Latino individuals showed a steady decline (AAPC: -0.68, p < 0.000001), while non-Hispanics showed rising mortality from 2018 to 2021 (APC: 2.92, p < 0.007) with a higher AAMR (126.59).Regionally, the Midwest had the highest AAMR for hematological malignancies (136.15), while the Northeast led in the sepsis group (10.8). By urbanization, micropolitan areas had the highest AAMR for hematological malignancies (130.9), with a declining trend (AAPC: -0.73, p < 0.000001). In contrast, large central metro areas had the highest AAMR for the sepsis cohort (10.62) with a sharp decline (AAPC: -1.09). Statistically significant declines were also noted in large fringe (AAPC: -1.18), medium (APC: -0.14), and small metro areas (APC: -0.04). This urban–rural reversal is unique to the sepsis cohort and highlights growing geographic disparities.States with the highest AAMRs for hematological malignancies included Minnesota (146.13), Iowa (142.66), and Nebraska (142.12); for hematological malignancies with sepsis, the highest rates were in the District of Columbia (13.61), New Jersey (13.62), and Rhode Island (13.02).

Conclusion:The study revealed a three-phase mortality pattern for hematologic malignancies, with a pivotal increase post-2018, especially for males and non-Hispanic individuals. Conversely, sepsis-associated mortality consistently declined across most demographics, including all racial categories. However, rural areas saw increases in sepsis-related mortality, highlighting an urban-rural healthcare gap. This disparity underscores the complex, divergent trends between these overlapping conditions.

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2025
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