How is neutropenia, specifically benign ethnic neutropenia (BEN), managed in the black population?

Management of Benign Ethnic Neutropenia (BEN) in the Black Population

Benign ethnic neutropenia should be recognized as a normal variant in Black individuals, with adjusted reference ranges for absolute neutrophil count (ANC) and no unnecessary dose reductions or treatment interruptions for those with this condition.

Understanding Benign Ethnic Neutropenia

Benign ethnic neutropenia (BEN) is a common condition affecting approximately 25-50% of individuals of African descent and some ethnic groups from the Middle East 1. It is characterized by:

• Consistently low absolute neutrophil counts without increased susceptibility to infection
• Normal bone marrow function and ability to produce neutrophils when needed
• Association with Duffy-null genotype (mutation in the ACKR1/DARC gene)
• No adverse clinical outcomes despite lower neutrophil counts

Diagnostic Considerations

Laboratory Features

• ANC values typically between 1,000-1,500 cells/μL (mild neutropenia)
• Can be as low as 1,210 cells/μL in individuals with Duffy-null status 2
• Persistent pattern of low neutrophil counts over time
• No associated symptoms or increased infection risk

Confirmatory Testing

• Review of historical CBC results showing consistent pattern of neutropenia
• Family history (often shows similar pattern in relatives)
• Consider Duffy antigen testing - absence of Fy(a) and Fy(b) blood group antigens is associated with BEN 3
• Normal bone marrow examination (rarely needed unless other concerning features present)

Clinical Management Algorithm

Step 1: Recognition and Diagnosis

• Identify consistent pattern of neutropenia in asymptomatic Black individuals
• Rule out other causes of neutropenia (medications, infections, hematologic disorders)
• Recognize BEN as a normal variant, not a pathological condition

Step 2: Avoid Unnecessary Interventions

• Do not perform extensive workup for neutropenia if pattern is consistent with BEN
• Avoid bone marrow examination unless other concerning features are present
• Do not restrict activities or implement infection precautions based solely on ANC values

Step 3: Medication Management

For patients receiving medications that may cause neutropenia:

1. For chemotherapy and IMiDs (Immunomodulatory drugs):

   • Do not inappropriately reduce doses of lenalidomide or pomalidomide due to perceived neutropenia 2
   • Consider BEN when establishing baseline neutrophil counts before treatment
   • Adjust neutropenia thresholds for dose modifications by 20-30% 2

2. For clinical trials:

   • Lower ANC enrollment thresholds by 20-30% for Black patients 2
   • Standard cutoff of ANC > 1500/μL can contribute to significant racial disparities in clinical trial participation 2

3. For G-CSF (Growth Factor) Use:

   • Reserve for true treatment-related neutropenia, not baseline BEN
   • Base decisions on trend of counts rather than absolute values

Special Considerations

HIV and Infection Risk

• BEN does not increase the risk of HIV acquisition or adverse events 4
• Patients with BEN do not have increased susceptibility to infections despite lower neutrophil counts

Neutropenic Fever Management

• Standard definition of neutropenic fever still applies (temperature ≥38.3°C with ANC <500 cells/μL) 5
• Follow standard neutropenic fever protocols when ANC drops below 500 cells/μL
• Remember that signs and symptoms of inflammation may be diminished in neutropenic patients 5

Cancer Treatment Considerations

• Disparities in cancer treatment outcomes between Black and White patients may be partially attributed to inappropriate dose reductions due to misinterpreted neutropenia 6
• Consider BEN when interpreting neutropenia in Black patients receiving chemotherapy

Common Pitfalls to Avoid

1. Misdiagnosis: Labeling BEN as pathological neutropenia leading to unnecessary workup
2. Overtreatment: Inappropriate use of G-CSF for baseline neutropenia
3. Undertreatment: Unnecessary dose reductions of critical medications
4. Exclusion from clinical trials: Using standard neutrophil cutoffs that don't account for BEN
5. Failure to recognize: Not considering BEN as a normal variant in Black individuals

Conclusion

BEN represents a normal variant in many Black individuals and should be recognized as such to avoid unnecessary testing, treatment interruptions, or exclusion from clinical trials. Adjusting reference ranges and clinical decision points for neutrophil counts in this population is essential for equitable healthcare delivery.