The changing face of stem cell transplantation by the use of recombinant human granulocyte colony stimulating factor.
The use of peripheral blood progenitor cells (PBPC) for autografting following high-dose chemotherapy in a variety of malignancies has increased markedly with the advent of efficacious and safe myeloid growth factors, which have dramatically improved collection yields. There is still controversy as to whether PBPC should be harvested after a combination of chemotherapy and growth factors, or after growth factors alone. The use of powerful combinations of newer growth factors, such as interleukin-3 with granulocyte-macrophage colony stimulating factor (GM-CSF), or granulocyte colony stimulating factor (G-CSF) with stem cell factor, may obviate the need for chemotherapy. The problem of providing sufficient numbers of PBPC for successful transplantation and sustained engraftment has led to the development of a variety of in vitro expansion systems for stem cells, using cocktails of growth factors. Single blood collections may contain sufficient CD34+ cells to be expanded on a large scale for clinical transplantation, eliminating costly and labour intensive apheresis procedures. PBPC transplants may carry less risk for contamination with malignant cells; however, sensitive detection techniques have revealed that tumour cell contamination of PBPC harvests may be much more prevalent than was previously suspected and both positive and negative selection of CD34+ cells for clinical transplantation is being investigated. PBPC transplantation generally results in more rapid engraftment, with faster recovery of neutrophils and platelets, compared with autologous bone marrow transplants. In most studies, PBPC transplants also resulted in fewer septic episodes, fewer intensive care admissions, fewer transfusions of red blood cells and platelets, reduced antibacterial and parenteral nutrition use, and reduced hospital costs. Dose optimisation and intensification of chemotherapy, relying on repeated administration of growth factor-mobilised PBPC, offers interesting prospects in the treatment of a variety of tumours. However, well-controlled, randomised prospective trials will be needed to prove the real value of PBPC transplants with regard to survival and cure. In the clinical setting, PBPC transplantations are likely to replace autologous marrow transplants in the near future. Manipulation of PBPC in vitro, i.e. expansion or gene transfer, may prove to be the most exciting perspective in the treatment of both malignant and non-malignant haematological conditions.
Boogaerts
M A
MA
Department of Hematology, University Leuven, U.Z. Gasthuisberg, Belgium.
Demuynck
H
H
D002455:Cell Division / Q000187:drug effects; D015672:Erythroid Precursor Cells / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000078224:Lenograstim; D009369:Neoplasms / Q000628:therapy; D011994:Recombinant Proteins / Q000008:administration & dosage; D013048:Specimen Handling
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim