Peripheral Blood Cytopenias Could Represent an Early Marker of Cancer Mortality Risk

Peripheral blood cytopenia is a persistent clinical challenge and, according to findings from the REGARDS trial, it may be associated with a higher risk of cancer-related mortality, particularly in Black patients. These findings suggest that cytopenia may be an early marker of severe disease, reported Diego Adrianzen Herrera, MD, of the Larner College of Medicine at the University of Vermont in Burlington, who presented the findings during the 2021 ASH Annual Meeting. 

REGARDS included 30,239 U.S. individuals who were followed with a semiannual phone interview through 2018 for cytopenia and cancer mortality.

The hazard of cytopenia-related cancer mortality was calculated in Cox proportional hazards models: Model 1 adjusted for demographics, Model 2 adjusted for Model 1 plus risk factors for cancer/anemia, and Model 3 adjusted for Model 1 plus socioeconomic factors. Additionally, the researchers assessed differences in the association of cytopenia and cancer death by race.

Of the 19,028 participants who were included in the analysis, 60% were White and 62% were female. There were 1,112 cancer deaths and 3,725 deaths from other causes during the median follow-up period of nine years. Approximately 2% (n = 383) of participants had cytopenia, including 65% (n = 25) of White patients and 35% (n = 113) of Black patients. The prevalence of cytopenia increased by advancing age and was highest in males (56%).

In all multivariate models, cytopenia was significantly associated with increased risk of cancer mortality, including in models adjusted for demographics (hazard ratio [HR] = 1.60), cancer risk factors (HR = 1.67), and socioeconomic variables (HR = 1.58). Additionally, both anemia and macrocytosis were associated with the risk of cancer-related death in all three hazard models.

The 10-year cumulative incidence of cancer-related death was significantly greater in patients with than without baseline cytopenia (13% vs. 6.5%, respectively; p < 0.01). In the analysis of race by cytopenia interaction, the HR for cancer mortality was significantly higher in Black patients compared with White patients in Model 1 (2.01 vs. 1.41, respectively; p = 0.016), Model 2 (2.12 vs. 1.45; p = 0.009), and Model 3 (1.82 vs. 1.44; p = 0.04).

Across all models, individual hematologic parameters with higher HR for cancer in Black versus White patients included anemia and macrocytosis. These findings could inform further studies aimed at clarifying racial disparities in cancer death through theorized mechanisms such as clonal hematopoiesis, the authors concluded.