Increased numbers of long-term culture-initiating cells in the apheresis product of patients randomized to receive increasing doses of stem cell factor administered in combination with chemotherapy and a standard dose of granulocyte colony-stimulating factor.
Long-term culture-initiating cells (LTC-IC) are arguably the most primitive human hematopoietic cells detectable by in vitro functional assays. We have investigated the mobilization of these cells into the blood of patients with ovarian carcinoma randomized to receive granulocyte colony-stimulating factor (G-CSF; 5 micrograms/kg) plus different doses of stem cell factor (SCF; c-kit ligand) after chemotherapy or G-CSF alone after chemotherapy. We have shown a significant SCF dose response for the mobilization of LTC-IC, with a 5.8-fold increase in LTC-IC mobilization in those patients receiving chemotherapy, G-CSF, and 20 micrograms/kg of SCF, the highest dose used, compared with the patients receiving chemotherapy and G-CSF alone. We have shown a threefold increase in CD34+ cells and up to a 64-fold increase in CD34+/33- cells was seen in patients treated with chemotherapy, G-CSF, and 20 micrograms/kg of SCF compared with those patients treated with chemotherapy and G-CSF alone. However, significant numbers of CD34+/38- cells were only found in the patients receiving 20 micrograms/kg of SCF as part of their mobilization regimen. Patients receiving chemotherapy plus G-CSF and SCF have enhanced mobilization of primitive cells and of the more committed progenitor cells compared with those patients receiving chemotherapy followed by G-CSF alone.
Cancer Research Campaign Department of Experimental Haematology, Christie Hospital, Manchester, UK.
A
A
Weaver
D
D
Ryder
D
D
Crowther
T M
TM
Dexter
N G
NG
Testa
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001781:Blood Component Removal; D002277:Carcinoma / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D002452:Cell Count / Q000187:drug effects; D002999:Clone Cells; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D007262:Infusions, Intravenous; D015080:Mesna / Q000008:administration & dosage; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D011994:Recombinant Proteins / Q000008:administration & dosage; D019089:Stem Cell Factor / Q000008:administration & dosage*; D013997:Time Factors
D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D015080:Mesna