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Flt-3 ligand synergizes with granulocyte colony-stimulating factor to
increase neutrophil numbers and to mobilize peripheral blood stem cells
with long-term repopulating potential
G Molineux, C McCrea, XQ Yan, P Kerzic and I McNiece
Department of Developmental Hematology, Amgen Inc, Thousand Oaks, CA 91320,
USA.
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
combination with granulocyte colony-stimulating factor (G-CSF). As a single
agent, FL was a relatively modest mobilizer of PBPCs, resulting in 360
granulocyte/macrophage colony-forming cells (GM-CFCs)/mL blood (control,
155 GM-CFCs/mL blood) and no advantage in leukocyte recovery when these
PBPCs were transplanted to irradiated recipient mice. G-CSF, on the other
hand, mobilized over 20,000 GM-CFCs/mL blood, and the combination of G-CSF
+ FL resulted in over 100,000 GM-CFCs/mL blood. The combination of G-CSF +
FL stimulated increased levels of monocytes and basophils in the peripheral
blood. The performance of the mobilized PBPC product in irradiated hosts
correlated with progenitor numbers resulting in long-term engraftment in
association with accelerated short-term recovery of both leukocytes and
platelets. These data demonstrate the 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 toxicities 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.
Volume 89,
Issue 11,
pp. 3998-4004,
06/01/1997
Copyright © 1997 by The American Society of Hematology
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