Genetic Testing for Benign Ethnic Neutropenia

Introduction

• Benign ethnic neutropenia (BEN) is a condition characterized by a low absolute neutrophil count (ANC) in otherwise healthy individuals, commonly affecting individuals of African, Middle Eastern, and West Indian descent, with a prevalence of 25-50% in these populations 1

Diagnosis and Testing

• Testing for the Duffy-null genotype (mutation in ACKR1/DARC gene) is available and recommended to confirm the diagnosis of BEN in patients with unexplained low neutrophil counts, particularly in patients from populations with high prevalence of the trait and those receiving medications where inappropriate dose reductions might occur due to perceived neutropenia (e.g., lenalidomide, pomalidomide) 1
• Genetic testing for Duffy-null genotype can confirm diagnosis of BEN, and reference range for neutrophils in individuals with Duffy-null status is approximately 1210-5390 cells/μL 1
• The American College of Hematology defines BEN as an absolute neutrophil count (ANC) <1500 cells/μL in otherwise healthy individuals with no increased risk of infection 1

Cancer Treatment

• In cancer treatment, particularly multiple myeloma, patients with Duffy-null status should not have lenalidomide or pomalidomide doses reduced based solely on low ANC values, as inappropriate dose reductions can lead to suboptimal treatment outcomes 1
• The National Comprehensive Cancer Network recommends that no specific treatment is required for BEN alone, and doses of lenalidomide or pomalidomide should not be reduced based solely on low ANC values in patients with confirmed BEN 1
• The Blood Cancer Journal notes that inappropriate dose reductions in patients with BEN may lead to suboptimal treatment outcomes, and BEN should not be a reason to exclude patients from clinical trials, as studies show no increased risk of adverse events in clinical trial participants with BEN 1

Clinical Implications

• Confirming Duffy-null status prevents unnecessary bone marrow biopsies, inappropriate medication dose reductions, exclusion from clinical trials, and misdiagnosis of neutropenia as pathological, and allows for appropriate medication dosing in cancer treatment regimens 1
• The Journal of the National Comprehensive Cancer Network states that G-CSF is NOT routinely indicated for BEN, and should be reserved for situations where neutropenia is caused by other factors (chemotherapy, congenital neutropenia) 2
• The Clinical Cancer Research journal states that using standard neutrophil cutoffs may inappropriately exclude patients with BEN from clinical trials 3
• Routine monitoring of neutrophil counts is unnecessary in asymptomatic individuals with established BEN, but for patients on medications that can cause neutropenia, monitor neutrophil counts as clinically indicated, consider baseline neutrophil values when interpreting results, and adjust treatment thresholds based on knowledge of BEN status 1

Guideline Recommendations