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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
A Weaver, D Ryder, D Crowther, TM Dexter and NG Testa
Cancer Research Campaign Department of Experimental Haematology, Christie
Hospital, Manchester, UK.
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.
Volume 88,
Issue 9,
pp. 3323-3328,
11/01/1996
Copyright © 1996 by The American Society of Hematology
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