Optimal use of cytokines/chemokines in peripheral blood stem cell transplantation

The last 3 years have witnessed a dramatic increase in the use of allogeneic peripheral blood stem cells (PBSCs) in lieu of bone marrow for allografting in patients with haematological malignancies in major bone marrow transplant centres worldwide. Based at least in part on experience with autologous transplantation, circulating haemopoietic progenitor cells are now known to include pluripotent stem cells expressing indefinite self-renewal capacity that can be employed for restoring haemopoiesis 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 and stem cells to guarantee engraftment. The administration of granulocyte colony-stimulating factor (G-CSF) has emerged as an efficient and usually well tolerated way to accomplish this mobilisation. For the donor, advantages of PBSC collection over traditional bone marrow harvesting include avoidance of anaesthesia and surgery, as well as the lack of need for blood transfusions or hospitalisation. In terms of clinical outcome, as compared with bone marrow-derived stem cells, the use of PBSCs seems to be associated with at least comparable (if not faster) recovery of leucocytes and platelets following transplantation. Allogeneic transplantation of PBSCs does not seem to be associated with a measurable increase in the incidence and severity of acute graft-versus-host disease (GVHD). Due to the >10-fold higher number of lymphoid subsets contained in a PBSC allograft, one might expect a faster immunological recovery and, possibly, a more pronounced graft-versus-leukaemia effect in the transplant patient. There are currently insufficient data available to address the issue of chronic GVHD. As with bone marrow cells, ex vivo manipulation of mobilised apheresis products (such as CD34+ cell selection, density gradient centrifugation and selection of graft-facilitating cells) is used or being developed to engineer allografts. It is expected that, based on the easier procurement of haemopoietic stem cells and advantageous engraftment characteristics, PBSCs may in the near future replace, at least in part, bone marrow-derived progenitor cells.