HEMATOPOIETIC GROWTH-FACTORS AND PERIPHERAL-BLOOD STEM-CELLS AS SUPPORTIVE AGENTS IN DOSE INTENSIFICATION

We have studied the requirements that have to be met to combine effect ive cancer chemotherapy with the mobilisation of peripheral blood stem cells (PBSC). We have shown that there is a differential induction of high numbers of PBSC following standard-dose chemotherapy (VIP) plus treatment with colony-stimulating factors. The combined sequential adm inistration of interleukin 3 (IL-3) plus granulocyte-macrophage colony -stimulating factor (GM-CSF) induced maximal numbers of PBSC, includin g colony-forming unit-granulocyte, erythrocyte, monocyte/macrophage, m egakaryocyte (CFU-GEMM) and colony-forming unit-megakaryocyte (CFU-Meg ), compared with the application of GM-CSF, granulocyte colony-stimula ting factor (G-CSF) or chemotherapy alone. The number of CD34+ cells w as highly variable depending on the prior treatment given to the patie nts. Mobilised CD34+ cells-depending on the cytokines used for recruit ment-had a varying cloning efficiency, and were heterogeneous as to th eir level of commitment. Retransfusion of G-CSF-primed progenitor cell s to pilot patients following high-dose chemotherapy demonstrated that PBSC recruited by standard-dose chemotherapy plus G-CSF accelerated b oth neutrophil and platelet recovery.