The use of mobilized peripheral blood stem cells from normal donors for allografting.

Peripheral blood stem cells (PBSCs) are gaining increasing acceptance as an alternative to bone-marrow (BM)-derived stem cells for allografting. Although scarce under steady-state conditions, CD34+ progenitor cells can be effectively mobilized into the peripheral blood (PB) in the vast majority of normal donors with a brief (3-4 days) course of recombinant human (rHu)G-CSF. Those cytokine-peripheralized progenitor cells and, among them, pluripotent stem cells, are collected by apheresis in sufficient amounts to achieve complete and permanent alloengraftment after myeloablative treatment in patients with primarily malignant hematologic disorders. The short-term tolerability profile of PBSC mobilization and apheresis in normal donors appears to be acceptable, although continued monitoring is necessary to ensure long-term safety. When compared with BM progenitor cells, mobilized PBSCs seem to exhibit a more primitive phenotype and a different clonogenic potential. The impact of factors affecting the efficiency of PBSC mobilization, such as rHuG-CSF dose, duration of cytokine treatment, and, to a lesser extent, donor age is now being recognized. Potential ways to optimize and possibly "engineer" PBSC collection, such as the use of cytokine/chemokine combinations (e.g., thrombopoietin, stem cell factor, etc.) and monoclonal antibodies directed against integrin receptors on CD34+ progenitor cells, are now being explored as well. In the clinical setting, engraftment after PBSC allografting is rapid and probably faster than after BM allografting. PBSC allografting seems to be associated with an incidence and severity of acute graft-versus-host disease (GVHD) comparable to the ones observed after BM allografting, although the incidence of chronic GVHD after allogeneic PBSC transplantation is still controversial. The infusion of a larger number of lymphoid cells appears to translate into a more rapid immunologic recovery and may lead to an enhanced graft-versus-leukemia effect. The collection of large numbers of mobilized PBSCs should provide ample opportunities for graft engineering and gene therapy. PBSCs may eventually replace, at least in part, BM as the preferred source of stem cells for both auto- and allotransplantation.