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 prim itive human hematopoietic cells detectable by in vitro functional assa ys, We have investigated the mobilization of these cells into the bloo d of patients with ovarian carcinoma randomized to receive granulocyte colony-stimulating factor (G-CSF; 5 mu g/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 mobili zation in those patients receiving chemotherapy, G-CSF, and 20 mu g/kg of SCF, the highest dose used, compared with the patients receiving c hemotherapy and G-CSF alone. We have shown a threefold increase in CD3 4(+) cells and up to a 64-fold increase in CD34(+)/33(-) cells was see n in patients treated with chemotherapy, G-CSF, and 20 mu g/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 mu g/kg of SCF as part of their mobilizat ion regimen. Patients receiving chemotherapy plus G-CSF and SCF have e nhanced mobilization of primitive cells and of the more committed prog enitor cells compared with those patients receiving chemotherapy follo wed by G-CSF alone. (C) 1996 by The American Society of Hematology.