Peripheral blood progenitor cell transplantation: a replacement for marrow auto- or allografts.

Abstract

Circulating hematopoietic progenitor cells include pluripotent stem cells expressing indefinite self-renewal capacity and, therefore, can be used for restoring hematopoiesis following myeloablative treatment. A transient shifting of progenitor cells from extravascular sites into the circulation by chemopriming and/or cytokine treatment enables the collection by apheresis of a sufficient number of progenitor cells to guarantee engraftment. The addition of new cytokines (e.g., thrombopoietin) and large volume apheresis will increase peripheral blood progenitor cell (PBPC) procurement efficiency, whereas the risk of concurrently mobilizing clonogenic tumor cells in patients with solid tumors and hematologic malignancies remains to be carefully evaluated. As compared with bone marrow (BM) progenitor cells, the use of PBPCs significantly shortens the recovery of WBC and platelets following transplantation. Most recently, successful allogeneic transplantation of PBPCs has been reported without increasing the incidence and severity of acute graft-versus-host-disease. Due to the more than one log higher number of lymphoid subsets contained in a PBPC allograft, one might expect a more pronounced graft-versus-leukemia effect in the transplant patient. Similar to BM cells, ex vivo manipulation of mobilized apheresis products is used or being developed (ultralight density percoll gradient, CD8 depletion, selection of graft facilitating cells, CD34+ cell purification and others). The transduction and long-term expression of marker genes and, most recently, therapeutic genes (e.g., MDR-1) in PBPCs have been successfully demonstrated by several groups in patients with hematologic malignancies and selected solid tumors. It is expected that, based on the easier procurement of hematopoietic stem cells and advantageous engraftment characteristics, PBPCs in both autologous and allogeneic transplant situations will eventually replace BM-derived progenitor cells.