What is Benign Ethnic Neutropenia and does it relate to low clozapine white counts?

Approximately one half of African Americans have neutrophil counts that are lower than the normal ranges reported by most laboratories. This may be related to a genetic polymorphism of the Duffy Antigen Receptor Chemokine (DARC) gene. Without any signs or symptoms of infection, the lower Absolute Neutrophil Count (ANC) is termed Benign Ethnic Neutropenia (BEN). Data suggest that having BEN does not put patients at risk of severe neutropenia. However, it previously precluded many people from being treated with clozapine due to ANCs lower than the specified US FDA monitoring values. In 2015, the FDA added a separate algorithm for ANC monitoring in patients with BEN. If patients of African or Middle Eastern descent have ANC values that run below 1500 cells/μL with no disease or medications contributing, a clinician can make a diagnosis of BEN without a hematology consultation and submit this diagnosis to the clozapine REMS system. BEN can also occur in other patients, but is rare. With BEN, patients can be safely treated at lower ANC values than usual. Routine genetic testing is not recommended. Patients who have BEN can be started on clozapine with two ANC values of greater than 1000 cells/μL. ANCs change over time and some patients may drop below 1000 periodically. Clozapine does not need to be discontinued unless the ANC drops below 500 cells/μL. The FDA monitoring protocol describes how and when to respond to low ANC results. For many with BEN, ANC values rise slightly after the initiation of clozapine. Also, morning neutropenia may contribute to low values so patients with suspected BEN can consider some activity before levels are drawn.

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