Phase I Trial of Recombinant Human Macrophage Colony-Stimulating Factor in Patients With Invasive Fungal Infections

• Published in: Blood Vol. 78; no. 4; pp. 907 - 913
• Main Authors: Nemunaitis, J., Meyers, J.D., Buckner, C.D., Shannon-Dorcy, K., Mori, M., Shulman, H., Bianco, J.A., Higano, C.S., Groves, E., Storb, R., Hansen, J., Appelbaum, F.R., Singer, J.W.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.08.1991; The Americain Society of Hematology
• Subjects: Adolescent; Adult; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Bone Marrow Transplantation; Child; Child, Preschool; Drug Evaluation; Female; Graft vs Host Disease - etiology; Hematopoiesis; Humans; Immune Tolerance; Macrophage Colony-Stimulating Factor - administration & dosage; Macrophage Colony-Stimulating Factor - adverse effects; Macrophage Colony-Stimulating Factor - therapeutic use; Male; Medical sciences; Mycoses - drug therapy; Mycoses - etiology; Mycoses - mortality; Pharmacology. Drug treatments; Recombinant Proteins - therapeutic use; Infection; Human; Treatment; Mycosis; Colony stimulating factor; Immunotherapy
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V78.4.907.907

A phase I dose escalation trial of recombinant human macrophage colony-stimulating factor (rhM-CSF) in combination with conventional antifungal therapy was conducted in 24 marrow transplant recipients with invasive fungal infection. Daily doses ranged from 100 to 2,000 µg/m2/d. Toxicity, such as constitutional symptoms, directly ascribed to rhM-CSF was not observed; however, transient, dose-related thrombocytopenia was observed. Patients who received 2,000 µg/m2/d of rhM-CSF had a mean reduction in platelet count of 61,000/mm3 during the rhM-CSF infusion period, which was significant when compared with patients who received lower doses of rhM-CSF (P = .008). Fourteen of the 16 patients who received rhM-CSF after undergoing allogeneic bone marrow transplantation had no change in the severity of graft-versus-host disease (GVHD) while receiving rhM-CSF. One had an increase in the severity of GVHD and one had a decrease. There were no effects on neutrophil, monocyte, or lymphocyte counts. Six patients had resolution of their infections, 12 were not evaluable for response, and six did not respond. Ten patients survived 100 days after initiation of rhM-CSF and 14 died. Further trials with rhM-CSF to assess antifungal activity are indicated.