Differential effects of granulocyte colony-stimulating factor on marrow- and blood-derived hematopoietic and immune cell populations in healthy human donors.
A recent phase III trial comparing granulocyte colony-stimulating factor (G-CSF)-stimulated bone marrow (G-BM) and G-CSF-mobilized peripheral blood (G-PB) in matched sibling allograft recipients showed that G-BM produced a similar hematologic recovery but a reduced incidence of extensive chronic graft-versus-host disease, indicating differences in the cell populations infused. As a first step toward identifying these differences, we treated a group of healthy adult humans with 4 daily doses of G-CSF 10 microg/kg and monitored the effects on various hematopoietic and immune cell types in the PB and BM over 12 days. G-CSF treatment caused rapid and large but transient increases in the number of circulating CD34+ cells, colony-forming cells, and long-term culture-initiating cells and in the short-term repopulating activity detectable in nonobese diabetic/severe combined immunodeficiency/beta2-microglobulin-null mice. Similar but generally less marked changes occurred in the same cell populations in the BM. G-CSF also caused transient perturbations in some immune cell types in both PB and BM: these included a greater increase in the frequency of naive B cells and CD123+ dendritic cells in the BM. The rapidity of the effects of G-CSF on the early progenitor activity of the BM provides a rationale for the apparent equivalence in rates of hematologic recovery obtained with G-BM and G-PB allotransplants. Accompanying effects on immune cell populations are consistent with a greater ability of G-BM to promote tolerance in allogeneic recipients, and this could contribute to a lower rate of chronic graft-versus-host disease.
Shier
Luke R
LR
Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
Schultz
Kirk R
KR
Imren
Suzan
S
Regan
Jill
J
Issekutz
Andrew
A
Sadek
Irene
I
Gilman
Andrew
A
Luo
Zhijuan
Z
Panzarella
Tony
T
Eaves
Connie J
CJ
Couban
Stephen
S
D000328:Adult; D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D008214:Lymphocytes / Q000276:immunology*; D012016:Reference Values
D015703:Antigens, CD; D018952:Antigens, CD34; D016179:Granulocyte Colony-Stimulating Factor