Background: Infection-related mortality remains a significant cause of death in patients with non-Hodgkin lymphoma (NHL), due to both disease-related immunosuppression and treatment-associated risks. This study analyzes national trends in infection-related mortality among NHL patients in the United States from 1999 to 2023, with emphasis on demographic disparities by sex, race/ethnicity, and geographic region.

Methods: Data were extracted from the CDC WONDER Multiple Cause of Death database. Age-adjusted mortality rates (AAMR) per million population were calculated. Trends were analyzed using Joinpoint regression analysis to determine annual percent changes (APC) over time and identify statistically significant inflection points. Analyses were stratified by sex, race/ethnicity, and U.S. Census region (Northeast, Midwest, South, West).

Results: The overall AAMR for infection-related mortality in NHL patients was 11.75 per million. A sharp decline occurred from 1999 to 2001 (APC: –9.2), followed by a slower decline from 2001 to 2013 (APC: –1.44). From 2013 to 2023, the trend plateaued (APC: –0.10, non-significant).

Sex-specific analysis identified higher mortality in males (AAMR: 15.77) compared to females (AAMR: 8.50). Among males, mortality declined sharply from 1999 to 2001 (APC: –14.56) and gradually from 2001 to 2023 (APC: –0.69). For females, mortality declined from 1999 to 2016 (APC: –1.66), followed by a non-significant increase from 2016 to 2023 (APC: +0.32).

Racial/ethnic stratification showed highest mortality in Black or African American patients (AAMR: 12.9), followed by Hispanic or Latino (12.4), White (11.5), and Asian or Pacific Islander patients (11.0). Black patients experienced a steep decline from 1999 to 2001 (APC: –24.23), followed by a significant rising trend from 2001 to 2023 (APC: –0.74, p < 0.05). Hispanic patients had a sharp early decline (APC: –9.20, 1999–2002), then a slower decline (APC: –0.65, 2002–2023). White patients saw a significant decline from 1999 to 2013 (APC: –1.88), followed by a plateau (APC: +0.20, 2013–2023, non-significant). Asian or Pacific Islander patients experienced a modest but consistent decline (APC: –1.07, 1999–2023).

Regional variations in AAMR were observed: Northeast (12.41), West (12.00), South (11.44), and Midwest (11.32). The Northeast showed a sharp decline from 1999 to 2001 (APC: –13.84), then a slower decrease through 2023 (APC: –1.52). The South also declined sharply from 1999 to 2001 (APC: –12.01) and moderately afterward (APC: –0.58). The Midwest and West showed moderate but consistent declines throughout the study period (APC: –0.91 and –0.98, respectively).

Conclusions: Infection-related mortality among NHL patients has declined over the past two decades, particularly in the early 2000s. However, recent stagnation in trends especially among females, White patients, and those in the Northeast and a rising trend in mortality among Black patients highlight emerging disparities. These findings underscore the need for targeted infection prevention strategies in high-risk subgroups, particularly defined by race/ethnicity, sex, and region.

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2025
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