Overview of Agranulocytosis Stan Gerson, MD Chief, Division of Hematology & Oncology Asa & Patricia Shiverick Professor of Hematological Oncology University Hospitals of Cleveland, Case Western Reserve University

Agranulocytosis l Drop in neutrophil count to less than 500/mm 3 l High incidence of neutropenic fever [>80%] l Duration of agranulocytosis directly impacts its severity and morbidity [fever in 100% of patients after 5 days] l Mortality is related to infections and their sequella l Rare in the absence of a serious illness or drug administration

Clozaril ® associated agranulocytosis l Serious disease in an affected individual l Represents a significant burden to health care l Early detection decreases risk

Key features of clozapine associated agranulocytosis l Onset in 1-3 weeks - detected by monitoring  Rapid onset is more severe  Benefit from early detection, drug is stopped prior to onset of symptoms l Often the drug is stopped with a WBC of and an ANC of l Unique features  Severe drop in granulocyte count [to 0] even after the drug is stopped  Prolonged duration [8d with growth factors, 15 d without]  Significant risk of neutropenic fever, severe internal infection

Management of agranulocytosis l Hospitalization of patient is recommended l Daily observation for fever, infection; culture and image of possible sites of infection l Antibiotics - either prophylactic or for fever l Hematopoietic growth factors [G-CSF, GM- CSF] l Duration of illness days l Substantial cost for treatment: hospitalization, antibiotics and growth factors

Advantages of monitoring system l Early detection prior to symptoms l Stop the drug early l Early initiation of treatment and management of agranulocytosis l Reassurance to patient, family and health care providers

Conclusions l Clozaril associated agranulocytosis is a serious illness l Monitoring allows detection prior to illness l Early detection can limit morbidity by prompt institution of management l Management is costly