Introduction

Hematological cancers—including leukemias, lymphomas, plasma cell disorders, myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs)—pose a significant public health challenge, accounting for considerable morbidity and mortality in the U.S. and globally. In 2024, an estimated 187,740 new cases and 57,260 deaths were reported among patients with hematological malignancies.1 With advances in therapy improving survival, attention has shifted from cancer-specific mortality to non-cancer causes of death. As treatment paradigms have evolved, so too may the risk factors for non-cancer mortality. This study investigates non-cancer causes of death and their relative risks in the overall population and various subgroups. These causes include infectious and parasitic diseases (including HIV), complications of medical and surgical treatment, chronic liver disease and cirrhosis, and suicide or self-inflicted injury.

Methods

We conducted a retrospective analysis of adult patients diagnosed with hematological cancers between 2000 and 2022 using the Surveillance, Epidemiology, and End Results (SEER) database, a U.S. population-based registry maintained by the National Cancer Institute (NCI). Included diagnoses were leukemias, lymphomas, plasma cell disorders, MDS, and MPNs. We calculated non-cancer mortality risk using standardized mortality ratios (SMRs) and 95% confidence intervals (CIs). SMR was defined as the ratio of observed non-cancer deaths to expected deaths in an age-matched general U.S. population over the same period. We stratified data by age (<50, 50–70, >70 years), gender (male, female), race (White/Caucasian, Black/African American, American Indian/Alaska Native [AI/AN], Asian/Pacific Islander), ethnicity (Non-Spanish-Hispanic-Latino [NSHL], Spanish-Hispanic-Latino [SHL]), and cause of non-cancer death.

Results

A total of 887,333 patients with hematological malignancies were included. Of these, 55.6% were male, 82.4% White/Caucasian, and 88.4% NSHL. Lymphoid neoplasms accounted for 58.2%, plasma cell disorders 13.6%, leukemias 9.1%, and MDS/MPN 18.8%. Across the full cohort, the highest risk of non-cancer death was due to homicide and legal interventions (SMR: 24.67, 95% CI: 20.32–29.69), followed by infectious and parasitic diseases including HIV (18.99, 18.55–19.45), complications of medical/surgical treatment (13.56, 12.36–14.85), chronic liver disease/cirrhosis (12.14, 11.61–12.68), and suicide/self-inflicted injury (10.29, 9.63–10.97). The highest SMRs within 12 months of diagnosis were from infectious and parasitic diseases including HIV (59.30, 57.43–61.22), homicide/legal intervention (35.98, 24.44–51.07), and chronic liver disease (21.10, 19.49–22.90).

In the subgroup analysis, among younger patients, risk of mortality associated with infectious and parasitic diseases including HIV was higher (45.23, 43.30–47.23), compared to older patients (2.91, 2.75–3.08). Tuberculosis-related mortality was elevated among Whites (3.20, 2.28–4.35) and Asian/Pacific Islanders (3.73, 2.37–5.60) compared to Blacks (2.21, 0.81–4.80). SHL patients had significantly higher SMRs for tuberculosis (10.09, 5.52–16.93 vs. 2.75, 2.08–3.57) and other infectious/parasitic diseases (16.83, 15.89–17.80 vs. 7.26, 7.07–7.45) compared to NSHL individuals.

Discussion

This large, population-based study highlights the substantial burden of non-cancer mortality in patients with hematological malignancies. Homicide and legal interventions were among the highest risk factors for death across all groups—an unexpected but critical finding. Social and psychological determinants likely play a role and warrant further investigation. Younger age and Hispanic ethnicity were associated with elevated risk of death from infectious causes, including HIV and tuberculosis. These findings emphasize the need for targeted public health strategies, including early psychosocial screening, infection prevention, and culturally sensitive interventions in high-risk groups. Future research should explore modifiable social determinants contributing to non-cancer mortality in this vulnerable population.

  1. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA: A Cancer Journal for Clinicians. 2024;74(1):12-49. doi:10.3322/caac.21820

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2025
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