Peripheral blood stem cells: in vivo biology and therapeutic potential

Abstract

Peripheral blood stem cells (PBSC) have been studied for their use after high-dose chemotherapy. The combination of a standard-dose chemotherapy [VIP: VP16 (etoposide), ifosfamide, cisplatin] in combination with hematopoietic growth factors was shown to provide effective anti-cancer activity as well as to enable sufficient stem cell mobilization for clinical use. Different growth factor regimens [granulocyte-colony-stimulating factor (G-CSF), granulocyte-macrophage (GM)-CSF, interleukin (IL)-3/GM-CSF] resulted in a differential induction of high levels of circulating PBSC after VIP chemotherapy, with the sequential combination of IL-3 and GM-CSF inducing maximal numbers of CD34+ cells as well as clonogenic progenitors. Our studies revealed a correlation between prior treatment and PBSC recruitment: the highest numbers of PBSC were mobilized in untreated patients whereas stem cell harvest was considerably impeded in heavily pretreated patients. Phase I/II trials demonstrated that transplantation of PBSC collected after VIP plus growth factor mobilization was safe, and engraftment was rapid and sustained. However, PBSC mobilization carried the risk of concomitant tumor cell recruitment in patients with detectable levels of tumor cells prior to therapy and in 21% of patients without circulating tumor cells. Positive selection of CD34+ cells by immunoadsorption that leads to an approximately three-log depletion of contaminating tumor cells therefore was investigated with regard to feasibility and capability as a source for PBSC transplantation. Twenty-one patients with advanced malignancies received autologous CD34+ cell transplantation after high-dose chemotherapy. Hematological recovery was as rapid as recorded for unseparated PBSC preparations, indicating that CD34+ cells can be safely used for autologous PBSC transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)