Contrasting effects of recombinant human granulocyte-macrophage colony-stimulating factor (CSF) and granulocyte CSF treatment on the cycling of blood elements in childhood-onset cyclic neutropenia

• Published in: Blood Vol. 84; no. 4; pp. 1257 - 1267
• Main Authors: WRIGHT, D. G, KENNEY, R. F, OETTE, D. H, LARUSSA, V. F, BOXER, L. A, MALECH, H. L
• Format: Journal Article
• Language: English
• Published: Washington, DC The Americain Society of Hematology 15-08-1994
• Subjects: Adolescent; Adult; Age of Onset; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Bone Marrow - pathology; Child; Colony-Forming Units Assay; Female; Granulocyte Colony-Stimulating Factor - therapeutic use; Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - pathology; Humans; Leukocyte Count - drug effects; Male; Medical sciences; Monocytes - drug effects; Neutropenia - blood; Neutropenia - drug therapy; Neutropenia - physiopathology; Neutrophils - drug effects; Pharmacology. Drug treatments; Platelet Count - drug effects; Recombinant Proteins - therapeutic use; Reticulocyte Count - drug effects; Time Factors; Human; Granulocyte colony stimulating factor; Treatment; Leukopenia; Polypeptide; Immunotherapy; Cytokine; Hemopathy; Child; Granulocyte macrophage colony stimulating factor; Neutropenia
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V84.4.1257.1257

Recombinant human granulocyte colony-stimulating factor (G-CSF) treatment has been shown to increase average neutrophil counts substantially in patients with childhood-onset cyclic neutropenia (or "cyclic hematopoiesis"), but not to eliminate the cyclic oscillations of neutrophil counts or those of other blood elements (monocytes, platelets, eosinophils, and reticulocytes) that are characteristic of this hematopoietic disorder. Indeed, oscillations of neutrophil counts are amplified during G-CSF treatment. We have compared the effects of recombinant granulocyte-macrophage-CSF (GM-CSF) with those of G-CSF in three patients with this disease (2 men and 1 woman, 17, 30, and 32 years of age). These patients were treated with GM-CSF (2.1 micrograms/kg/day, subcutaneously) for 6 weeks, preceded and followed by 6 to 13 weeks of detailed observation to document changes in the cyclic oscillations of blood neutrophils and other blood elements; two of the patients were subsequently treated with G-CSF (5.0 micrograms/kg/d, subcutaneously) and observed for comparable periods of time. Unlike G-CSF treatment, which increased average neutrophil counts more than 20-fold, GM-CSF increased neutrophil counts only modestly, from 1.6- to 3.9-fold, although eosinophilia of varying prominence was induced in each patient. However, at the same time, GM-CSF treatment dampened or eliminated the multilineage oscillations of circulating blood elements (neutrophils, monocytes, platelets, and/or reticulocytes) in each of the patients. In contrast, G-CSF treatment of the same patients markedly amplified the oscillations of neutrophil counts and caused the cycling of other blood elements (monocytes in particular) to become more distinct. These findings support the conclusion that the distinctive cycling of blood cell production in childhood-onset cyclic neutropenia results from abnormalities in the coordinate regulation of both GM-CSF-responsive, multipotential progenitor cells and G-CSF-responsive, lineage-restricted, neutrophil progenitors.