Hematopoietic Growth Factors Alone

Several hematopoietic growth factors have been used to mobilize PBSC including G-CSF, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and SCF. Currently, G-CSF is the most commonly used agent to mobilize PBSC because of its potency and lack of serious toxicity. There are several common features observed during mobilization with hematopoietic growth factors.16 First, mobilization kinetics are similar, with peak levels of circulating HPCs generally achieved after 5-10 days of growth factor.

Second, a broad spectrum of HPCs is mobilized, including pluripotential, and committed myeloid, megakaryocyte, and erythroid progenitors. Third, the increase in circulating HPCs is associated with decreased numbers of HPCs in BM. And finally, mobilized HPCs have characteristic phenotypic features distinct from those of HPCs that reside in the BM under steady-state conditions. Relative to BM, a higher percentage of mobilized PBSC are in the G0 or G1 phase of cell cycle, and the expression of VLA-4 and c-kit on their surfaces is reduced. A recent study showed that HPCs are selectively mobilized after the M phase of cell cycle thus providing a potential explanation for preponderance of HPCs in the G0 or G1 phase of the cell cycle in blood.

The mechanism by which growth factors mobilize PBSC is not clearly understood. Recent animal studies have provided some insight into stem cell trafficking in the BM and the role of adhesion molecules in HPC mobilization.16-18 The model of HPC mobilization by G-CSF is shown in Figure 94.2.

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