A Role for granulocyte-macrophage colony-stimulating factor (GM-CSF) in the treatment of neutropenic patients with pneumonia

ABSTRACT

Pneumonia is a serious, difficult to manage, and often fatal infection in neutropenic patients. The availability of hematopoietic growth factors has made it possible to evaluate the role of reversing the neutropenic state. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been used in an investigator-initiated, open-label clinical trial in approximately 1200 patients. Data colleted on each patient was reviewed to identify all patients who had the combination of neutropenia and pneumonia. Sixty-eight patients (5 percent of the patients for whom GM-CSF was requested) met the criteria for having neutropenic peneumonia. In this patient population there were 45 males and 20females (gender was not indicated in 3). Ages ranged from 3 to 83 years (mean 39 ñ 18 years). The underlying diseases included 7 patients who were receiving chemotherapy for solid malignant tumors, 14 for lymphoma, and 22 for leukemia; 15 post bone marrow transplantation primarily for hematologic malignancy; 3 idiosyncratic drug-induced neutropenia; and 7 with other causes of neutropenia. The type of pneumonia was predominantly fungal in 21 patients, bacterial in 23, viral in 2, protozoal in 1, and uncertain in 21 (presumed to be bacterial in 19 and viral in 2). Patients received a mean of 5µg/kg GM-CSF (range 1.3-12.5µg/kg) daily for a mean of 13 ñ 10 (range 2-57) days. The mean leukocyte count at start of treatment was 600 ñ 500 cells/mmü, and at the end of treatment was 5600 ñ 9200 cells/mmü (P=0.001). The time between start of GM-CSF and a leukocyte level in excess of 1500/mmü was a median of 13 days. Hematopoietic recovery was showm in 46/62 (74 percent), 40/64 (63 percent) showed good clinical and/or radiologic improvement, and 41/68 (60 percent) survived. Four illustrative case reports are provided. By comparing the hematologic responders to non-responders, it is clear that persistent neutropenia contributed significantly to poor clinical outcome and mortality. Only 3/22 (13 percent) of non-responders survived, whereas 38/46 (83 percent) of responders survived. There were 7 adverse events (rash 1, fever/chills 2, malaise 1, myalgia/bone pain 2, increased myeloblasts 1) which were considered to be related to use of the cytokine. Aggravation of the pulmonary inflammation or sepis syndrome was not observed. Tolerability was good or very good in 89 percent of patients. Based on this open-label study, the use of GM-CSF in combination with appropiate antibiotics ...