Mobilization of HSC Mechanisms

1
Mobilization of HSC Mechanisms
Cytokine receptor
Vascular endothelium
HSCs
CXCR4
SDF-1 gradient
Notch1/ Jagged1
VLA4/ VCAM1
c-Kit SCF
Extracellular matrix proteins and soluble
cytokines
Stromal cells
2
(No Transcript)
3
The Size of the ProblemGITMO
Relapsed/refractory
CT-naive
28
15
13
7
Poor mob.
Poor mob.
No mob.
No mob.
4
(No Transcript)
5
(No Transcript)
6
(No Transcript)
7
The use of AMD 3100 plus G-CSF for autologous
hematopoietic progenitor cell mobilization is
superior to G-SCF alone
Flomenberg N et al, Blood First Edition Paper
2005, May12/Blood 2005-02-0468
8
Apheresis Results after G and AG Priming
Flomenberg N et al, Blood First Edition Paper
2005, May12/Blood 2005-02-0468
9
The use of AMD 3100 plus G-CSF for autologous
hematopoietic progenitor cell mobilization is
superior to G-SCF alone
Flomenberg N et al, Blood First Edition Paper
2005, May12/Blood 2005-02-0468
10
AMD3100CXCR4 Antagonist

• Limited toxicity as single agent
• Clinical activity in pre-treated MM and NHL
  patients
• Synergism with G-CSF in humans
• Competitive repopulation studies
• Effects in poor mobilizers
• Effects on GvHD vs GVL (?)