Benign Ethnic Neutropenia and Clozapine Use: A Systematic Review of the Evidence and Treatment Recommendations

Objective: To evaluate the epidemiology, pathobiology, and management of benign ethnic neutropenia and determine the extent to which these factors should influence measures designed to avoid clozapine-induced agranulocytosis.

Data Sources: A structured MEDLINE search with no language limitation was performed from database inception until March 31, 2015, using the terms clozapine and benign ethnic neutropenia. Retrieved articles were cross-checked for additional relevant studies.

Study Selection: Included in the study were articles that reported on the prevalence, etiology, and complications of benign ethnic neutropenia and the hematologic outcome of clozapine treatment in patients with this condition.

Data Extraction: Study results that documented the epidemiology, pathobiology, and clozapine utilization in persons of African, Arabian, and Mediterranean descent with a neutrophil count in the 1,000-1,800/mm3 range.

Results: The search identified 342 publications. Forty-two articles described the epidemiology, pathobiology, and management of benign ethnic neutropenia. Of these, 12 articles described patients with benign ethnic neutropenia whose neutrophil count decreased during treatment with clozapine. Persons with benign ethnic neutropenia do not have signs of impaired phagocytosis, and the frequency, severity, and outcome of their infections are similar to those observed in the general population. These features suggest that a neutrophil count > 1,000/mm3 is safe for initiating and/or resuming clozapine therapy.

Conclusions: The presence of benign ethnic neutropenia should not prevent treatment with clozapine. Patients with benign ethnic neutropenia who develop a clozapine-induced decrease in the neutrophil count, but have no evidence of infection or impaired phagocytosis, may resume clozapine as soon as they have > 1,000 neutrophils/mm3.