Background: Premature mortality from hematologic malignancies represents a major source of life-years lost, and trends and disparities in this burden are not well-characterized. Modern therapies have dramatically improved outcomes, yet it is unclear whether these gains have extended uniformly to younger and middle-aged populations. We analyzed national trends in premature mortality, defined as death before age 55 from hematologic malignancies, and assessed differences across demographic and geographic subgroups.

Methods: We used CDC WONDER mortality data from 1999 to 2020 for individuals under 55 years with hematologic malignancy as the underlying cause of death (ICD-10 codes C81-C96). Age-adjusted mortality rates (AAMR) per 100,000 person-years were calculated by race/ethnicity, sex, urbanization, and geographic census region. Joinpoint regression estimated Annual Percent Change (APC) and identified significant trend changes. Linear models with Year × Group interactions tested whether the rate of decline differed across subgroups.

Results: AAMR decreased from 3.7 per 100,000 in 1999 to 1.9 in 2020, corresponding to an overall APC of -2.95% (p<0.001). All subgroups experienced statistically significant reductions (p<0.05 for APC), although there were differences among subgroups. When analyzed by region, the Midwest exhibited the most pronounced decline (APC -3.90% from 1999-2005 and -4.73% from 2015-2020), while the South had the least AAMR reduction (APC -2.71%). The Northeast showed a consistent decline over the entire period, with no jointpoints detected and an APC of -3.44%. Racial differences were evident throughout the study period; non-Hispanic Black individuals had the highest mortality (4.7 to 2.7 per 100,000; APC -2.66%), whereas Asian/Pacific Islander individuals had the lowest (2.4 to 1.1; APC -3.05%). Non-Hispanic White individuals showed the largest absolute decrease (APC -3.22%). Mortality among males consistently exceeded that among females (2020: 2.3 vs 1.6 per 100,000), though the magnitude of decline was similar between sexes. There were greater reductions in urban areas (APC -3.11%) compared with rural areas (APC -2.70%).

Conclusion: Mortality from hematologic malignancies among U.S. individuals under 55 years declined substantially from 1999 to 2020; however, persistent disparities by race, geography, and urbanization remain significant. Non-Hispanic Black individuals and people living in rural and Southern regions saw significantly slower declines in AAMR. Given the curative potential of modern therapies in this younger population, these gaps may reflect inequities in access to or delivery of care. However, additional data are needed to determine the underlying causes.

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2025
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