BIOLOGICAL PROPERTIES OF PERIPHERAL-BLOOD PROGENITOR CELLS MOBILIZED BY CYCLOPHOSPHAMIDE AND GRANULOCYTE-COLONY-STIMULATING FACTOR

Patients transplanted with mobilized blood progenitor cells (PBPC) rec over their neutrophil counts more rapidly than patients transplanted w ith bone marrow even when they receive the same dose/kg of granulocyte -macrophage colony-forming cells (CFU-GM). Here we have sought a biolo gical explanation for this phenomenon. Most CD34-positive PBPC are qui escent (<1% in S phase) when they are collected from the bloodstream o f patients treated with cyclophosphamide and granulocyte colony-stimul ating factor (G-CSF), but we have shown that they are able to resume p roliferation rapidly in vitro by measuring the kinetics of CFU-GM prod uction by primitive plastic-adherent (P Delta) cells. Also, P Delta ce lls in PBPC harvests, unlike normal marrow P Delta cells, were insensi tive to cell-cycle restraint imposed by contact with marrow-derived st romal cells. We found that P Delta cells in PBPC collections produce r elatively more CFU-GM and relatively fewer BFU-E than P Delta cells in bone marrow, indicating that granulopoiesis might occur at the expens e of erythropoiesis, but we were unable to find any differences in the kinetics of granulocytic maturation between PBPC and bone marrow. Our interpretation of these findings is that transplanted PBPC rapidly en ter the cell cycle and contact with stromal cells in the marrow does n ot reduce the proportion of progenitors participating in neutrophil pr oduction. Consequently, neutrophil recovery after PBPC infusion is mor e rapid than neutrophil recovery after marrow infusion. Granulopoiesis at the expense of erythropoiesis may also contribute to this effect.