Introduction Myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) are clonal hematologic diseases characterized by dysregulated blood cell production. While much research focuses on progression to acute leukemia, non-cancer-related mortality—such as infections, septicemia, vascular events, and liver-related deaths—has become increasingly recognized. This study aims to characterize the leading causes of non-cancer mortality in patients with MPDs and MDS, using data from a large, representative U.S. population cohort.

Methods We conducted a retrospective analysis of 166,785 adults diagnosed with MPN or MDS between 2000 and 2022, using the SEER database. Standardized Mortality Ratios (SMRs) with 95% confidence intervals (CI) were calculated by comparing observed non-cancer deaths to expected deaths in an age-, sex-, race-, ethnicity-, and calendar-year matched U.S. population. We stratified by age (<50, 50–70, >70 years), sex, race (White, Black, American Indian/Alaska Native [AI/AN], Asian/Pacific Islander), ethnicity (non-Spanish-Hispanic Latino [NSHL] vs. Spanish-Hispanic Latino [SHL]) and major categories of non-cancer causes of death.

Results Among 166,785 patients were diagnosed with MPN and MDS between the year 2000-2022,in which 43.8% had MDS; 54.6% were male, 82.6% were White, and 90.8% were NSHL. In overall overall cohort with MPN and MDS, tuberculosis had the highest mortality (7.22, 4.94–10.20), followed by infectious and parasitic diseases including HIV at (4.31, 4.00–4.65), septicemia (3.80, 3.59–4.02), chronic liver disease (3.88, 3.59–4.17), vascular disease including arteries/arterioles/capillaries (3.11, 2.75–3.51), and stomach/duodenal ulcers (3.08, 2.46–3.81). Within the first 12 months post-diagnosis, tuberculosis was associated with increased risk of death (12.60, 6.29–23.00), followed by septicemia (6.48. 5.84–7.18).

In younger patients (<50 years), vascular disease was associated with higher mortality (10.43, 3.83–22.69 vs 2.74, 2.36–2.17), as compared to older groups. AI/AN individuals were at markedly elevated risk death due to chronic liver disease/cirrhosis (16.36, 7.48–31.05), vascular disease (14.98, 1.81–54.10), and infections including HIV (11.81, 3.84–27.57). SHL patients had dramatically higher mortality from tuberculosis (29.13, 11.71–60.02 vs 5.97; 3.86–8.81), and from infectious/parasitic diseases (6.11, 4.80–7.66 vs 4.16, 3.84–4.51), as compared to NSHL.

Discussion In this large, population-based SEER cohort, non-cancer mortality among MPN and MDS patients was significantly elevated, with tuberculosis, septicemia, infections, chronic liver disease, ulcers, and vascular disease emerging as leading causes. The markedly elevated SMRs for tuberculosis and septicemia during the first-year post-diagnosis highlight early vulnerability. Younger patients exhibited disproportionately high vascular mortality, and AI/AN and SHL groups showed striking disparities across infection and liver-related deaths.

These findings likely reflect biological vulnerabilities—such as immune dysregulation, comorbid conditions, and therapy-related effects—and social or structural determinants. They underscore the need for early risk stratification, aggressive infection surveillance, targeted vascular risk management, and culturally competent supportive care. Previous SEER-Medicare literature has also documented inferior survival among MPN patients compared to controls, particularly for myelofibrosis, and highlighted high cardiovascular mortality in MPN cohorts, with about 25% of deaths attributed to cardiovascular causes.

In practice, these data support the integration of multidisciplinary interventions—including infectious disease prevention, hepatology evaluation, vascular risk assessment, and social determinants-informed strategies—to mitigate preventable non-cancer mortality in MPN/MDS populations.

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2025
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