FLT-3 LIGAND SYNERGIZES WITH GRANULOCYTE-COLONY-STIMULATING FACTOR TOINCREASE NEUTROPHIL NUMBERS AND TO MOBILIZE PERIPHERAL-BLOOD STEM-CELLS WITH LONG-TERM REPOPULATING POTENTIAL

Flt-3 ligand (FL) shares many features with stem cell factor (SCF), a widely documented cofactor for peripheral blood progenitor cell (PBPC) mobilization. We investigated the mobilization of PBPCs by FL in comb ination with granulocyte colony-stimulating factor (G-CSF). As a singl e agent, FL was a relatively modest mobilizer of PBPCs, resulting in 3 60 granulocyte/macrophage colony-forming cells (GM-CFCs)/mL blood (con trol, 155 GM-CFCs/mL blood) and no advantage in leukocyte recovery whe n these PBPCs were transplanted to irradiated recipient mice, G-CSF, o n the other hand, mobilized over 20,000 GM-CFCs/mL blood, and the comb ination of G-CSF + FL resulted in over 100,000 GM-CFCs/mL blood. The c ombination of G-CSF + FL stimulated increased levels of monocytes and basophils in the peripheral blood. The performance of the mobilized PB PC product in irradiated hosts correlated with progenitor numbers resu lting in longterm engraftment in association with accelerated short-te rm recovery of both leukocytes and platelets, These data demonstrate t he potential of FL to synergize with G-CSF to mobilize PBPCs with both short- and long-term engraftment potential. The effect is similar to the synergistic interaction of G-CSF and SCF on PBPC mobilization, The use of FL as opposed to SCF may elicit a different spectrum of toxici ties including lymphoid proliferation effects, in contrast to the mast cell degranulation effects of SCF. Clinical studies of FL are needed to evaluate its usefulness in man. (C) 1997 by The American Society of Hematology.