title: Granulocyte and granulocyte-macrophage colony-stimulating factors for treatment of neutropenia in glycogen storage disease type Ib.
abstract: Two children with glycogen storage disease type Ib associated with numerous recurrent bacterial infections as a result of neutropenia and neutrophil dysfunction were treated with recombinant human granulocyte colony-stimulating factor (G-CSF). One of the two patients was previously treated with recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF); therapy had to be discontinued because of severe local side effects. Both colony-stimulating factors at dosages of 3 and 8 micrograms/kg/per day, respectively, increased the average neutrophil counts from less than 300 cells/microliters to more than 1200 cells/microliters. Two subpopulations of neutrophils could be identified by their capacity to produce H2O2: one subpopulation generated H2O2 normally and a second was defective in H2O2 production. The doses of G-CSF effectively enhanced and maintained that subpopulation of neutrophils which produced normal amounts of H2O2. Moreover, these colony-stimulating factor-induced neutrophils demonstrated effective phagocytosis of zymosan particles and killing of staphylococci. Chemotaxis was decreased and could not be normalized by treatment with G-CSF. We conclude that maintenance treatment with G-CSF improved the quality of life in both patients: The number and severity of bacterial infections decreased markedly during treatment. Long-term treatment with G-CSF (12 and 10 months, respectively) was well tolerated, and no adverse clinical events were observed.
authors.affiliation: University Children's Hospital, Düsseldorf, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Schroten
authors.forename: J
authors.initials: J
authors.lastname: Roesler
authors.forename: T
authors.initials: T
authors.lastname: Breidenbach
authors.forename: U
authors.initials: U
authors.lastname: Wendel
authors.forename: J
authors.initials: J
authors.lastname: Elsner
authors.forename: S
authors.initials: S
authors.lastname: Schweitzer
authors.forename: C
authors.initials: C
authors.lastname: Zeidler
authors.forename: S
authors.initials: S
authors.lastname: Burdach
authors.forename: M L
authors.initials: ML
authors.lastname: Lohmann-Matthes
authors.forename: V
authors.initials: V
authors.lastname: Wahn
mesh_terms: D000293:Adolescent; D001433:Bacteriolysis; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D005953:Glycogen Storage Disease Type I / Q000503:physiopathology / Q000628:therapy*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007223:Infant; D007279:Injections, Subcutaneous; D007958:Leukocyte Count; D008297:Male; D009503:Neutropenia / Q000503:physiopathology / Q000628:therapy*; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D011994:Recombinant Proteins; D013211:Staphylococcus aureus / Q000502:physiology; D013481:Superoxides / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D013481:Superoxides; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006861:Hydrogen Peroxide