RAPID ENGRAFTMENT BY PERIPHERAL-BLOOD PROGENITOR CELLS MOBILIZED BY RECOMBINANT HUMAN STEM-CELL FACTOR AND RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR IN NONHUMAN-PRIMATES

We have previously shown that administration of low-dose recombinant h uman stem cell factor (rhSCF) plus recombinant human granulocyte colon y-stimulating factor (rhG-CSF) to baboons mobilizes greater numbers of progenitor cells in the blood than does administration of rhG-CSF alo ne. The purpose of the present study was to determine whether marrow r epopulating cells are present in the blood of nonhuman primates admini stered low-dose rhSCF plus rhG-CSF, and if present, whether these cell s engraft lethally irradiated recipients as rapidly as blood cells mob ilized by treatment with rhG-CSF alone. One group of baboons was admin istered low-dose rhSCF (25 mu g/kg/d) plus rhG-CSF (100 mu g/kg/d) whi le a second group received rhG-CSF alone (100 mu g/kg/d). Each animal underwent a single 2-hour leukapheresis occurring the day when the num ber of progenitor cells per volume of blood was maximal. For baboons a dministered low dose rhSCF plus rhG-CSF, the leukapheresis products co ntained 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 transplantati on of cryopreserved autologous blood cells. In animals transplanted wi th low-dose rhSCF plus rhG-CSF mobilized blood cells, we observed a ti me to a platelet count of >20,000 was 8 days +/- 0, to a white blood c ell count (WBC) of >1,000 was 11 +/- 1 days, and to an absolute neutro phil count (ANC) of >500 was 12 +/- 1 days. These results compared wit h 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 rhS CF plus rhG-CSF mobilized blood cells had blood counts equivalent to p retransplant values within 3 weeks after transplant. The results sugge st that the combination of low-dose rhSCF plus rhG-CSF mobilizes great er 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 mobil ized by low-dose rhSCF plus rhG-CSF engraft lethally irradiated recipi ents more rapidly than do blood cells mobilized by rhG-CSF alone. (C) 1995 by The American Society of Hematology.