Use of Granulocyte-Macrophage Colony Stimulating Factor for Treatment of Drug-Induced Agranulocytosis

Abstract

SIR-Granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) represent two hematopoietic growth factors that have the potential to alter the therapeutic management of the febrile granulocytopenic patient [1, 2]. Recently, a patient with apparent drug-induced agranulocytosis presented us with the opportunity to test the effect of GM-CSF in this clinical setting. Two days before admission to the hospital, a 61-year-old man with chronic obstructive pulmonary disease, diabetes mellitus, congestive heart failure, and tachycardia developed a high fever and shaking chills. His medications on admission included captopril, procainamide hydrochloride, bumetanide, and chlorpropamide, each of which has been reported to cause agranulocytosis [3]. On physical examination the patient appeared ill and had a temperature of 39.2?C. Signs of congestive heart failure and localized areas of cellulitis around the right orbit and over the left tibia were noted. Laboratory tests revealed a total white blood cell (WBC) count of 700/mm3 (no polymorphonuclear cells [PMNs]), a hemoglobin concentration of 12.1 g/dL, and a platelet count of 259,000/mm3. All of his medications were discontinued. Despite treatment with three antibacterial agents, fever to 40?C and chills persisted. Cultures of blood, urine, and an aspirate from a skin lesion were negative for pathogens. On day 4 a bone marrow aspirate and biopsy demonstrated profound myeloid hypoplasia with promyelocytes seen only rarely. Because of persistent agranulocytosis and the failure of antibiotic therapy, subcutaneous treatment with human recombinant GM-CSF (5 /g/[kg-d], Schering SCH 039300, provided by Dr. Howard Grossberg, Schering, Kenilworth, NJ) was initiated on day 5. Within 2 days, the patient was afebrile and had improved remark-