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Cytopenia Associated With Increased Risk of Cancer Death, Particularly in Black Patients

January 13, 2022

Mid-January 2022

Peripheral blood cytopenia is a persistent clinical challenge that may be associated with an increased risk of cancer-related mortality, particularly in Black patients, suggesting cytopenia may be an early marker of severe disease. This is according to research presented during the 2021 ASH Annual Meeting by Diego Adrianzen Herrera, MD, of the Larner College of Medicine at the University of Vermont in Burlington.

The research was part of the REGARDS trial, which prospectively enrolled 30,239 individuals from the U.S. between 2003 and 2007. The investigators identified cancer death rates via a semi­annual phone follow-up period through 2018. In the study, cytopenia was defined by the presence of at least two of the following criteria:

  • hemoglobin below age, sex, and race-specific lowest 5th percentile
  • white cell count below race-specific lowest 5th percentile
  • platelet count below lowest 5th percentile
  • macrocytosis (MCV >98 fL)

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, while Inverse Odds Ratio Weighting (IORW) mediation analysis was used to assess the effect of cytopenia as a mediator in the race-to-cancer mortality interaction.

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; 95% CI 1.16-2.21), cancer risk factors (HR=1.67; 95% CI 1.2-2.32), and socioeconomic variables (HR=1.58; 95% CI 1.12-2.23). 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 (Model 1: 1.98 vs. 1.76, p<0.001; Model 2: 1.95 vs. 1.73, p<0.001; Model 3: 1.80 vs. 1.54, p<0.001) and macro­cytosis (Model 1: 1.78 vs. 1.57, p<0.001; Model 2: 1.59 vs. 1.36, p=0.012; Model 3: 1.68 vs. 1.60, p<0.001). In the mediation analysis by IORW estimation method, the researchers did not find cytopenia to be a significant mediator in the pathway between the association of race and cancer death.

The researchers concluded that their findings can possibly “inform further studies aimed at clarifying racial disparities in cancer death through theorized mechanisms such as clonal hematopoiesis.”

Any conflicts of interest declared by the authors can be found in the original abstract.


Herrera DA, Koh I, Gangaraju R, Akinyemiju T, Zakai NA. Peripheral Blood Cytopenia and Risk of Cancer Mortality. Abstract #177. Presented at the 2021 American Society of Hematology Annual Meeting, December 11, 2021.


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