THE MOBILIZATION OF PRIMITIVE HEMATOPOIETIC PROGENITORS INTO THE PERIPHERAL-BLOOD

There is considerable interest in the use of peripheral blood progenit or cells (PBPC) for hemopoietic rescue following high dose chemotherap y. Current regimens mobilize CD34(+) with variable efficacy and there remains considerable empiricism in the design of these regimens. Some involve myelosuppression, some the administration of various cytokines alone or in combination, while a combination of chemotherapy and cyto kines is employed in others. Certain protocols result in mobilization within one week while in others, maximal PBPC levels occur only after several weeks. Thus, procedures required for optimal mobilization of P BPC remain to be defined. An understanding of the mechanisms responsib le for mobilization may lead to the development of improved mobilizati on strategies. Herein we review data that explore the mechanisms invol ved in the mobilization of PBPC in man. These data demonstrate that mo bilization is associated with marked changes in the expression and fun ction of cell adhesion molecules (CAMs) on hemopoietic progenitor cell s (HPC), suggesting that the release of HPC into the blood involves a perturbation of the adhesive interactions between these cells and the marrow stroma that, in steady-state conditions, serve to restrict WC t o the bone marrow. Downregulation of c-kit is invariably associated wi th successful mobilization which, when combined with data from in vitr o studies, implies a key role for stem cell factor (SCF) as an orchest rator of mobilization.