Mortality trends of sepsis in patients with leukemia in the United States (1999–2020): A CDC wonder database analysis

Abstract Background: Patients with leukemia are more likely to develop sepsis as a result of disease-related immunosuppression and cytotoxic therapy. While sepsis outcomes have improved, the national mortality burden from leukemia-associated sepsis is still unknown. Objective: To investigate national death rates among persons aged ≥25 years with concurrent diagnoses of leukemia and sepsis using CDC WONDER data from 1999 to 2020. Methods: From 1999 to 2020, we searched the CDC WONDER Multiple Cause of Death database for fatalities attributed to leukemia (ICD-10: C91-C95 subcodes) and sepsis (ICD-10: A40-A41 subcodes). Adults aged 25 and above were divided into decade age groups. Age-adjusted mortality rates (AAMRs) per 100,000 people were determined using the 2000 US standard population. Joinpoint regression was used to assess temporal patterns and identify the annual percent change (APC) with statistical significance (p < 0.05). Results: We identified 63770 sepsis-related deaths in leukemia patients from 1999 to 2020. An overall decline in AAMR occurred (APC: -0.83; 95% CI, -1.02 to -0.63; p= <0.000001) from 1990 (1.49) to 2020 (1.21) in all age groups with greatest reduction in 55-64 years age group (APC: -1.46; 95% CI, -1.82 to -1.10; p= <0.000001) while rate remained stable in those aged >85 years (APC: -0.07; 95% CI, -0.49 to 0.35; p= 0.716474). Although men had higher AAMR than women (1.84 vs 0.97), women had consistent decline from 1990 to 2020 (APC: -0.91; 95% CI, -1.17 to -0.65; p= 0.000001), while men had a greater rate of decline from 2010-2020 with APC of -1.50 (95% CI, -1.90 to -1.10; p= 0.000001). Analysis by race showed the highest AAMR among Black or African American individuals (1.51), followed by non-Hispanic individuals (1.33), White individuals (1.33), Hispanic individuals (1.12), Asian or Pacific Islander individuals (0.90), and American Indian or Alaska Native individuals (0.69). Regionally, the Northeast region showed the highest AAMR (1.39), followed by the South (1.34), the Midwest (1.31), and the West (1.28). Among all 52 states, West Virginia had the highest AAMR (1.63). Both metro and non-metro areas showed a declining trend of mortality, with the decline being faster in metro (APC: -0.91; 95% CI, -1.05 to -0.78; p <0.000001) areas as compared to non-metro areas (APC: -0.21; 95% CI, -0.65 to 0.23; p 0.329715). Conclusions: While overall mortality from leukemia-associated sepsis declined in the United States over the last two decades, the burden is still significant among the elderly and minorities. Targeted therapies and early detection techniques for sepsis in immunocompromised individuals are crucial for improving outcomes.