Haematopoietic growth factors and peripheral blood stem cells as supportive agents in dose intensification

Abstract

We have studied the requirements that have to be met to combine effective 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 administration of interleukin 3 (IL-3) plus granulocyte-macrophage colony-stimulating factor (GM-CSF) induced maximal numbers of PBSC, including colony-forming unit-granulocyte, erythrocyte, monocyte/macrophage, megakaryocyte (CFU-GEMM) and colony-forming unit-megakaryocyte (CFU-Meg), compared with the application of GM-CSF, granulocyte colony-stimulating factor (G-CSF) or chemotherapy alone. The number of CD34+ cells was highly variable depending on the prior treatment given to the patients. Mobilised CD34+ cells--depending on the cytokines used for recruitment--had a varying cloning efficiency, and were heterogeneous as to their level of commitment. Retransfusion of G-CSF-primed progenitor cells to pilot patients following high-dose chemotherapy demonstrated that PBSC recruited by standard-dose chemotherapy plus G-CSF accelerated both neutrophil and platelet recovery.