title: 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.
abstract: 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.
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, Bethesda, MD.
authors.forename: D G
authors.initials: DG
authors.lastname: Wright
authors.forename: R F
authors.initials: RF
authors.lastname: Kenney
authors.forename: D H
authors.initials: DH
authors.lastname: Oette
authors.forename: V F
authors.initials: VF
authors.lastname: LaRussa
authors.forename: L A
authors.initials: LA
authors.lastname: Boxer
authors.forename: H L
authors.initials: HL
authors.lastname: Malech
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D003114:Colony-Forming Units Assay; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D009000:Monocytes / Q000187:drug effects; D009503:Neutropenia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D009504:Neutrophils / Q000187:drug effects; D010976:Platelet Count / Q000187:drug effects; D011994:Recombinant Proteins / Q000627:therapeutic use; D017701:Reticulocyte Count / Q000187:drug effects; D013997:Time Factors
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor