SUPERIOR ANTILEUKEMIC ACTIVITY OF MURINE PERIPHERAL-BLOOD PROGENITOR-CELL (PBPC) GRAFTS MOBILIZED BY G-CSF AND STEM-CELL FACTOR (SCF) AS COMPARED TO G-CSF ALONE

We have established a murine model to compare the antileukemic effect of PBPC grafts obtained after treatment with SCF + G-CSF and G-CSF alo ne. C57/BL6, DBA and Balb/c mice were splenectomized and injected with optimal doses of rhG-CSF (250 mu g/kg/day s.c.) or rrSCF (100 mu g/kg /day s.c.) or with a combination thereof. On day 5, we determined the hematopoietic potential (number of CD34(+) cells, CFUs, total CFC, CFU -gm), the proportion of lymphoid (T, NK and B cells) and myeloid compo nents and graft-versus-leukemia activity after allogeneic and syngenei c PBPCT and BMT in Balb/c mice bearing a B-lymphoblastic leukemia cell line (A20), The absolute number of progenitor cells increased two-fol d after administering a combination of G-CSF and SCF as compared to G- CSF alone (1500 vs 940 CD34(+) cells/mu l; 190 vs 70 total CFC/mu l; 1 50 vs 50 CFU-gm/mu l and 6600 vs 3000 CFUs/ml), Although no difference s could be detected in the cellular composition, especially in the num ber of T cells, PBPC grafts mobilized by the combination of G-CSF + SC F demonstrated significantly higher antileukemic activity compared to G-CSF alone (94% vs 71% freedom from leukemia, P < 0.05). Because the incidence of lethal GVHD was similar in both groups, improved GVL acti vity resulted in superior overall survival. Our data suggest that the higher number of progenitor cells can be harvested after G-CSF + SCF a nd that grafts mobilized by G-CSF + SCF exert significantly enhanced a ntileukemic activity compared to those harvested after treatment with G-CSF alone.