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 alone. C57/BL6, DBA and Balb/c mice were splenectomized and injected with optimal doses of rhG-CSF (250 microg/kg/day s.c.) or rrSCF (100 microg/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 components and graft-versus-leukemia activity after allogeneic and syngeneic PBPCT and BMT in Balb/c mice bearing a B-lymphoblastic leukemia cell line (A20). The absolute number of progenitor cells increased two-fold after administering a combination of G-CSF and SCF as compared to G-CSF alone (1500 vs 940 CD34+ cells/microl; 190 vs 70 total CFC/microl; 150 vs 50 CFU-gm/microl and 6600 vs 3000 CFUs/ml). Although no differences could be detected in the cellular composition, especially in the number of T cells, PBPC grafts mobilized by the combination of G-CSF + SCF 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 activity resulted in superior overall survival. Our data suggest that the higher number of progenitor cells can be harvested after G-CSF + SCF and that grafts mobilized by G-CSF + SCF exert significantly enhanced antileukemic activity compared to those harvested after treatment with G-CSF alone.
Department of Internal Medicine II, University of Kiel, Germany.
G
G
Hartung
L
L
Uharek
M
M
Zeis
B
B
Glass
J
J
Steinmann
P
P
Dreger
M
M
Krönke
N
N
Schmitz
D000818:Animals; D020350:Graft vs Tumor Effect / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D007942:Leukemia, Experimental / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D019089:Stem Cell Factor / Q000494:pharmacology*; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor