Granulocyte colony-stimulating factor-induced mobilization of peripheral blood stem cells for autologous and allogeneic transplantation

Abstract

 Peripheral blood stem and progenitor cells (PBSC and PBPC), which circulate at very low levels during steady-state hematopoiesis, show a transient but marked increase during hematologic recovery from marrow-suppressive chemotherapy. To ensure rapid and sustained hematologic engraftment after autologous PBSC transplantation, sufficient PBSC or PBPC must be infused. To confirm the utility of granulocyte colony-stimulating factor (G-CSF) in chemotherapy-induced PBSC mobilization, we investigated the effect of G-CSF on PBSC mobilization in leukemia and lymphoma patients. The study design was such that PBSC mobilization with and without G-CSF was assessed in the same patients. The results indicate that PBSC mobilization can be enhanced significantly when G-CSF is given during the recovery phase postchemotherapy. Interestingly, progenitor cells of different lineages could be mobilized by G-CSF. We subsequently investigated the effect of increasing G-CSF dose on PBSC mobilization during steady-state hematopoiesis in healthy adult donors. The results indicate that not only committed but also primitive progenitor cells are mobilized into the circulation in a dose- and time-dependent manner when G-CSF at 5, 10, or 15 μg/kg was given on each of 5 days and leukapheresis was performed on day 6. From our data we estimate that sufficient PBSC for engraftment after allogeneic PBSC transplantation can be collected on day 5 of administration of G-CSF at 10 μg/kg and by 10-l leukapheresis on days 5 and 6. Furthermore, we found that some G-CSF-mobilized PBSC retained their self-renewal capability. These observations suggest that hematopoietic stem cells for allogeneic PBSC transplantation can be mobilized by short-term administration of relatively high-dose G-CSF.