title: Phase I/II study of combined granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor administration for the mobilization of hematopoietic progenitor cells.
abstract: OBJECTIVE
  To study the toxicity and efficacy of combined granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) administration for mobilization of hematopoietic progenitor cells (HPCs).
  
  
  METHODS
  Cohorts of a minimum of five patients each were treated subcutaneously as follows: G-CSF 5 micrograms/kg on days 1 to 12 and GM-CSF at .5, 1, or 5 micrograms/kg on days 7 to 12 (cohorts 1, 2, and 3); GM-CSF 5 micrograms/kg on days 1 to 12 and G-CSF 5 micrograms/kg on days 7 to 12 (cohort 4); and G-CSF and GM-CSF 5 micrograms/kg each on days 1 to 12 (cohort 5). Ten-liter aphereses were performed on days 1 (baseline, pre-CSF), 5, 7, 11, and 13. Colony assays for granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E) were performed on each harvest.
  
  
  RESULTS
  The principal toxicities were myalgias, bone pain, fever, nausea, and mild thrombocytopenia, but none was dose-limiting. Four days of treatment with either G-CSF or GM-CSF resulted in dramatic and sustained increases in the numbers of CFU-GM per kilogram collected per harvest that represented 35.6 +/- 8.9- and 33.7 +/- 13.0-fold increases over baseline, respectively. This increment was attributable both to increased numbers of mononuclear cells collected per 10-L apheresis and to increased concentrations of progenitors within each collection. The administration of G-CSF to patients already receiving GM-CSF (cohort 4) caused the HPC content to surge to nearly 80-fold the baseline (P = .024); the reverse sequence, ie, the addition of GM-CSF to G-CSF, was less effective. The CFU-GM content of the baseline aphereses correlated with the maximal mobilization achieved (r = .74, P = .001).
  
  
  CONCLUSIONS
  Combined G-CSF and GM-CSF administration effectively and predictably mobilizes HPCs and facilitates apheresis.
authors.affiliation: Robert Lurie Cancer Center, Northwestern University, Chicago, IL 60611, USA.
authors.forename: J N
authors.initials: JN
authors.lastname: Winter
authors.forename: H M
authors.initials: HM
authors.lastname: Lazarus
authors.forename: A
authors.initials: A
authors.lastname: Rademaker
authors.forename: M
authors.initials: M
authors.lastname: Villa
authors.forename: C
authors.initials: C
authors.lastname: Mangan
authors.forename: M
authors.initials: M
authors.lastname: Tallman
authors.forename: L
authors.initials: L
authors.lastname: Jahnke
authors.forename: L
authors.initials: L
authors.lastname: Gordon
authors.forename: S
authors.initials: S
authors.lastname: Newman
authors.forename: K
authors.initials: K
authors.lastname: Byrd
authors.forename: B W
authors.initials: BW
authors.lastname: Cooper
authors.forename: N
authors.initials: N
authors.lastname: Horvath
authors.forename: E
authors.initials: E
authors.lastname: Crum
authors.forename: E A
authors.initials: EA
authors.lastname: Stadtmauer
authors.forename: E
authors.initials: E
authors.lastname: Conklin
authors.forename: A
authors.initials: A
authors.lastname: Bauman
authors.forename: J
authors.initials: J
authors.lastname: Martin
authors.forename: C
authors.initials: C
authors.lastname: Goolsby
authors.forename: S L
authors.initials: SL
authors.lastname: Gerson
authors.forename: J
authors.initials: J
authors.lastname: Bender
authors.forename: M
authors.initials: M
authors.lastname: O'Gorman
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001781:Blood Component Removal; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000628:therapy; D002408:Catheters, Indwelling / Q000009:adverse effects; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007239:Infections / Q000209:etiology; D007279:Injections, Subcutaneous; D007958:Leukocyte Count / Q000187:drug effects; D008223:Lymphoma / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy; D009325:Nausea / Q000139:chemically induced; D009504:Neutrophils / Q000187:drug effects; D010146:Pain / Q000139:chemically induced; D010976:Platelet Count / Q000187:drug effects; D011237:Predictive Value of Tests; D013921:Thrombocytopenia / Q000139:chemically induced; D014839:Vomiting / Q000139:chemically induced
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor