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Rapid engraftment by peripheral blood progenitor cells mobilized by
recombinant human stem cell factor and recombinant human granulocyte
colony-stimulating factor in nonhuman primates
RG Andrews, RA Briddell, GH Knitter, SD Rowley, FR Appelbaum and IK McNiece
Division of Clinical Research, Fred Hutchinson Cancer Research Center,
Seattle, WA 98104.
We have previously shown that administration of low-dose recombinant human
stem cell factor (rhSCF) plus recombinant human granulocyte
colony-stimulating factor (rhG-CSF) to baboons mobilizes greater numbers of
progenitor cells in the blood than does administration of rhG-CSF alone.
The purpose of the present study was to determine whether marrow
repopulating cells are present in the blood of nonhuman primates
administered low-dose rhSCF plus rhG-CSF, and if present, whether these
cells engraft lethally irradiated recipients as rapidly as blood cells
mobilized by treatment with rhG-CSF alone. One group of baboons was
administered low-dose rhSCF (25 micrograms/kg/d) plus rhG- CSF (100
micrograms/kg/d) while a second group received rhG-CSF alone (100
micrograms/kg/d). Each animal underwent a single 2-hour leukapheresis
occurring the day when the number of progenitor cells per volume of blood
was maximal. For baboons administered low-dose rhSCF plus rhG-CSF, the
leukapheresis products contained 1.8-fold more mononuclear cells and
14.0-fold more progenitor cells compared to the leukapheresis products from
animals treated with rhG-CSF alone. All animals successfully engrafted
after transplantation of cryopreserved autologous blood cells. In animals
transplanted with low-dose rhSCF plus rhG-CSF mobilized blood cells, we
observed a time to a platelet count of > 20,000 was 8 days +/- 0, to a
white blood cell count (WBC) of > 1,000 was 11 +/- 1 days, and to an
absolute neutrophil count (ANC) of > 500 was 12 +/- 1 days. These
results compared with 42 +/- 12, 16 +/- 1, and 24 +/- 4 days to achieve
platelets > 20,000, WBC > 1,000, and ANC > 500, respectively, for
baboons transplanted with rhG-CSF mobilized blood cells. Animals
transplanted with low-dose rhSCF plus rhG-CSF mobilized blood cells had
blood counts equivalent to pretransplant values within 3 weeks after
transplant. The results suggest that the combination of low-dose rhSCF plus
rhG-CSF mobilizes greater numbers of progenitor cells that can be collected
by leukapheresis than does rhG-CSF alone, that blood cells mobilized by
low-dose rhSCF plus rhG-CSF contain marrow repopulating cells, and finally
that using a single 2-hour leukapheresis to collect cells, the blood cells
mobilized by low-dose rhSCF plus rhG-CSF engraft lethally irradiated
recipients more rapidly than do blood cells mobilized by rhG- CSF alone.
Volume 85,
Issue 1,
pp. 15-20,
01/01/1995
Copyright © 1995 by The American Society of Hematology
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