Immune mediated agranulocytosis and anemia associated with thymoma

Abstract

Thymoma has been associated with a variety of autoimmune disorders. We report a case of agranulocytosis and anemia in a 68-year-old woman with a spindle cell thymoma. She was unresponsive to treatment with antibiotics, granulocyte-colony stimulating factor (G-CSF), prednisone, and high-dose intravenous immunoglobulin. Serial bone marrow examinations on this therapy showed progression from a cellular marrow with mild myeloid and erythroid hyperplasia and lymphocytosis, to granulocyte aplasia and severe erythroid hypoplasia. Her serum contained granulocyte-specific antibodies and inhibited the growth in culture of her own marrow cells and marrow cells from a normal donor. An IgG fraction from her serum also inhibited the growth of marrow cells. Although the patient's spindle cell thymoma was surgically removed, she remained neutropenic. She was treated with six plasma exchanges followed by 1,000 milligrams of intravenous cyclophosphamide 2 days after the final plasma exchange and daily G-CSF. Three weeks later her peripheral blood showed marked leukocytosis with pronounced neutrophilia and a left shift. Although her agranulocytosis resolved, she died of fungal sepsis. This case demonstrates that aggressive plasma exchange and immunosuppressive therapy may benefit patients with agranulocytosis associated with thymoma.