What is the treatment approach for benign ethnic neutropenia (BEN)?

Management of Benign Ethnic Neutropenia (BEN)

Benign ethnic neutropenia (BEN) requires no specific treatment as it is a normal variant in certain populations and does not increase infection risk. 1

Definition and Prevalence

• BEN is defined as an absolute neutrophil count (ANC) <1500 cells/μL in otherwise healthy individuals with no increased risk of infection 1, 2
• Most commonly affects individuals of African, Middle Eastern, and West Indian descent, with prevalence of 25-50% in these populations 2
• Associated with the Duffy-null genotype (mutation in ACKR1/DARC gene), found in approximately two-thirds of Black patients in the US 3

Clinical Characteristics

• Patients with BEN have lower baseline ANC values but are NOT at higher risk for infections or other adverse events 3
• Reference range for neutrophils in individuals with Duffy-null status is approximately 1210-5390 cells/μL 3
• BEN is clinically insignificant and represents a normal variant rather than a pathological condition 4

Diagnostic Approach

1. Establish pattern of neutropenia:

   • Document persistent neutropenia over time
   • Confirm absence of symptoms or history of recurrent infections
   • Consider family history (often present in relatives) 5

2. Rule out other causes:

   • Exclude viral infections, hematological malignancies, autoimmune diseases, and nutritional deficiencies 5
   • Consider medication-induced neutropenia

3. Confirmatory testing (if needed):

   • Serological analysis for absence of Duffy (Fy) blood group antigens Fy(a) and Fy(b) 5
   • Genetic testing for Duffy-null genotype can confirm diagnosis 3

Management Recommendations

General Management

• No specific treatment is required for BEN alone 1
• Avoid unnecessary evaluations, referrals, and interventions 1
• Patient education about the benign nature of this condition is essential

Special Considerations for Medication Management

1. Chemotherapy and IMiDs (Immunomodulatory drugs):

   • Do not reduce doses of lenalidomide or pomalidomide based solely on low ANC values in patients with confirmed BEN 3
   • Consider BEN (ideally with genotyping confirmation) before reducing doses of medications that can cause neutropenia 3
   • Inappropriate dose reductions in patients with BEN may lead to suboptimal treatment outcomes 3

2. Clinical Trial Participation:

   • BEN should not be a reason to exclude patients from clinical trials 6
   • Studies show no increased risk of adverse events in clinical trial participants with BEN 6

3. G-CSF Administration:

   • G-CSF is NOT routinely indicated for BEN 3
   • Reserve G-CSF for situations where neutropenia is caused by other factors (chemotherapy, congenital neutropenia) 3, 7

Monitoring

• Routine monitoring of neutrophil counts is unnecessary in asymptomatic individuals with established BEN
• For patients on medications that can cause neutropenia:
  • Monitor neutrophil counts as clinically indicated
  • Consider baseline neutrophil values when interpreting results
  • Adjust treatment thresholds based on knowledge of BEN status

Common Pitfalls to Avoid

1. Overdiagnosis and overtreatment: Recognizing BEN prevents unnecessary evaluations, referrals, and interventions 1

2. Medication underdosing: Inappropriate dose reductions of cancer therapies due to perceived neutropenia can lead to suboptimal treatment outcomes 3

3. Exclusion from clinical trials: Using standard neutrophil cutoffs may inappropriately exclude patients with BEN from clinical trials 3

4. Misclassification as pathological: Labeling normal phenotypes in non-White populations as "abnormal" contributes to systemic racism in medicine 4

By recognizing BEN as a normal variant and adjusting clinical decision-making accordingly, healthcare providers can avoid unnecessary interventions while ensuring optimal treatment for patients with this common condition.