Phase I/II study of combined granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor administration for the mobilization of hematopoietic progenitor cells.
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.
Winter
J N
JN
Robert Lurie Cancer Center, Northwestern University, Chicago, IL 60611, USA.
Lazarus
H M
HM
Rademaker
A
A
Villa
M
M
Mangan
C
C
Tallman
M
M
Jahnke
L
L
Gordon
L
L
Newman
S
S
Byrd
K
K
Cooper
B W
BW
Horvath
N
N
Crum
E
E
Stadtmauer
E A
EA
Conklin
E
E
Bauman
A
A
Martin
J
J
Goolsby
C
C
Gerson
S L
SL
Bender
J
J
O'Gorman
M
M
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
D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor