What’s in a Label? Rethinking "Benign Ethnic Neutropenia"

By Stephen Hibbs

My primary research focuses on sickle cell disease, using ethnographic methods to explore the lived experiences of patients. However, during a seven-month journey through the research ethics approvals process, I found time to investigate a different question that had concerned me for years.

The issue in question? A label: “benign ethnic neutropenia.”

What is “Benign Ethnic Neutropenia”?

This term describes the observation that some people, particularly those with ancestry in parts of Africa or the Middle East, have naturally lower levels of a type of white blood cell called neutrophils. Neutrophils play a key role in fighting infections, so when a patient has a low neutrophil count, it often prompts medical investigations. If no other cause is found and the person’s ethnicity “fits”, they might be labeled with “benign ethnic neutropenia.”

But this label is deeply problematic.

  • Is it truly “benign”? While it’s true these individuals aren’t at greater risk of infections, the lower neutrophil count has significant, often harmful, clinical implications through misinterpretation (as I’ll explain below).
  • Why “ethnic”? Ethnicity is not a fixed biological category—it is a socially constructed, fluid concept.
  • What about “neutropenia”? This term assumes that a lower neutrophil count is abnormal, reflecting historical power dynamics in defining what’s “normal.” In a different world, I might be labeled as having “benign ethnic neutrophilia” if lower counts were the baseline.

The Link to Malaria

The story becomes clearer when we look at malaria. People in malaria-endemic regions often carry a protective genetic variation called “Duffy null.” This variant prevents a type of malaria parasite (Plasmodium vivax) from infecting red blood cells. However, it’s also associated with lower circulating neutrophil levels.

In other words, Duffy null status explains much of what’s been labeled “benign ethnic neutropenia”.1 This connection has been known since around 2009, but it wasn’t until 2023 that the first neutrophil reference range specifically for Duffy null individuals was published. This new range goes as low as 1200 cells/μL, compared to the widely used cutoff of 2000 cells/μL in the UK and US.2

Real-World Consequences: Cancer Care

These differences in reference ranges aren’t just theoretical—they have real-world consequences, particularly in cancer care. Working with collaborators in East London and Boston, I designed a study to examine the impact on cancer trials and treatments.

Here’s what we found3:

  1. Cancer trial eligibility: Many clinical trials exclude participants with “abnormal” neutrophil counts, often setting the cutoff at <1500 cells/μL. This means 10–15% of Duffy null individuals are automatically excluded from trials, even though their neutrophil counts are normal for them.
  2. Cancer treatment guidelines: For the five most common cancers, about half of first-line chemotherapy prescribing guidelines recommend dose reductions, delays, or modifications based on neutrophil counts below the standard range. For Duffy null individuals, this could mean less intensive treatment, despite their counts being completely normal for their genetic background. Treatment intensity closely relates to chance of cure, so this finding needs careful attention.

In a further discussion piece4, we additionally highlighted neutrophil cutoffs found in criteria used for reporting adverse events (CTCAE) and some types of cancer remission criteria. These also need re-examination in the light of Duffy null neutrophil variation.

Duffy Null

Connections to My PhD

How does this connect with my ethnographic work on sickle cell disease?

  1. Rethinking race and ethnicity in medicine: Both examples—sickle cell disease and benign ethnic neutropenia—show how concepts like “race” and “ethnicity” are applied in healthcare. Sickle cell disease is often incorrectly described as a “Black disease,” but it’s found across many racialised groups. India, for instance, has the second-largest population of people with sickle cell disease, who are not racialised as Black. Labels based on “ethnicity” or “race” often obscure more than they reveal.
  2. Studying the invisible infrastructure: My research is guided by the sociologist Susan Leigh Star’s call to “study boring things”.5 What might seem dull—like trial eligibility criteria or drug labels—often hides powerful, taken-for-granted assumptions. These are shaped by history, reinforced by bureaucracy, and can perpetuate inequality. By unpacking them, we can uncover opportunities for meaningful change.

This project, though different in methodology, echoes some of the broader questions at the heart of my PhD: how do labels, systems, and assumptions shape healthcare experiences, and how might we do better?

  1. Merz LE, Hibbs SP. Invisible Infrastructure in Haematology: Neutrophil Reference Ranges and the Duffy-null Phenotype. HemaSphere. 2023;7(11):e972. doi:10.1097/HS9.0000000000000972
  2. Merz LE, Osei MA, Story CM, et al. Development of Duffy Null-Specific Absolute Neutrophil Count Reference Ranges. JAMA. 2023;329(23):2088-2089. doi:10.1001/jama.2023.7467
  3. Hibbs SP, Aiken L, Vora K, et al. Cancer Trial Eligibility and Therapy Modifications for Individuals With Duffy Null–Associated Neutrophil Count. JAMA Network Open. 2024;7(9):e2432475. doi:10.1001/jamanetworkopen.2024.32475
  4. Hantel A, Hibbs SP, Merz LE, Abel GA. The Duffy Null Phenotype — Addressing a Source of Discrimination in Cancer Care. New England Journal of Medicine. 2024;391(21):1969-1972. doi:10.1056/NEJMp2409329
  5. Star SL. The Ethnography of Infrastructure. American Behavioral Scientist. 1999;43(3):377. doi:10.1177/00027649921955326

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