National Trends and Disparities in Sepsis-Related Mortality in Adults with Hematological Cancers, 1999-2020

Introduction

Hematological cancers and their treatments increase the risk of sepsis and up to 30% are diagnosed with sepsis in the first year. Hematological cancer-related sepsis carries a substantial mortality rate, but no population-based study has evaluated longitudinal trends in mortality in the United States (US). We aimed to examine the temporal trends in sepsis-related mortality in adults with hematological malignancies and whether any racial differences existed in the US from 1999 through 2020.

Methodology

We conducted a retrospective, serial cross-sectional analysis of national death certificate data from the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research database from 1999 to 2020. We used the International Classification of Diseases 10th Revision codes (ICD-10) to identify persons aged ≥25 years with hematological malignancies as the underlying cause of death and any mention of sepsis as a contributing cause of death. Deaths from viral, fungal, and parasitic illnesses were excluded. The exposure was the year of death, and the outcome was sepsis-related age-adjusted mortality rate (AAMR). The AAMR was calculated per 100,000 population and further stratified by age, gender, race, and census region. Race was ascertained based on death certificate reporting and CDC categorization. Metropolitan areas were classified as urban, and other areas were classified as rural. The racial differences were evaluated using the non-Hispanic Black (NHB) to non-Hispanic White (NHW) AAMR ratio. The Mann-Whitney U test was used to compare two groups and ANOVA was used to compare groups of ≥3. P<0.05 defined statistical significance. Temporal trends were evaluated with Joinpoint regression, expressed as an average annual percentage change (AAPC) with 95% confidence intervals (CI).

Results

Among 4.5 billion adults, there were 122,379 sepsis-related deaths in those with hematologic malignancies, with an overall AAMR of 3.4. Males, who made up 58.7% of the population, had a significantly higher AAMR (3.4) compared to females (1.9; P < 0.00001). The racial composition was 74.7% non-Hispanic White (NHW), 12.9% non-Hispanic Black (NHB), and 8.6% Hispanic. NHB had the highest AAMR of 3.4, while NHW and Hispanics had AAMRs of 2.5, and these differences were significant (P < 0.0001). Most deaths occurred in adults aged 65 to 74 years (28%). There were no significant differences in AAMR among census regions or between urban and rural areas. The overall NHB to NHW AAMR ratio was 1.3 and there was no significant change over the study period. Overall, the AAMR decreased from 3.0 to 2.0 (AAPC: 1.92%, 95% CI: -2.1 to -1.5). Declines were also observed in both males (4.0 to 2.7; AAPC -1.74%, 95% CI: -2.0 to -1.4) and females (2.3 to 1.5; AAPC -1.70%, 95% CI: -2.0 to -1.4). For Hispanic individuals, the AAMR decreased from 2.9 to 2.0 (AAPC -1.31%, 95% CI: -1.7 to -0.9). NHB individuals saw a reduction with an AAPC of -2.1% (95% CI: -2.6 to -1.4), and NHW individuals experienced a decline with an AAPC of -1.5% (95% CI: -1.7 to -1.3). In rural areas, the AAMR decreased from 2.8 to 2.0 (AAPC -1.1%, 95% CI: -1.4 to -0.7), while urban areas saw a decline with an AAPC of -2.0% (95% CI: -2.2 to -1.8).

Conclusion

Our study revealed a significant decline in sepsis-related mortality among adults with hematologic malignancies. This trend may be attributed to advances in medical treatment, improved infection control and prevention practices, and the early diagnosis and treatment of sepsis. Despite this progress, substantial racial disparities were observed. Non-Hispanic Black individuals experienced the highest mortality rates and these disparities persisted throughout the study period. The racial disparity may be due to differences in health-seeking behavior or lack of access to healthcare. There is a need to identify the reasons or drivers of these differences to develop interventions to improve outcomes for all racial groups.