Clinical utilisation of human haematopoietic progenitors elicited in peripheral blood by recombinant human granulocyte colony-stimulating factor (rHuG-CSF)

Abstract

INTRODUCTION IN ADULTS, haematopoietic progenitors circulate in the peripheral blood under physiological conditions. In these conditions, i.e. in the steady state, the compartment of circulating progenitors comprises granulocyte-macrophage, erythroid and bipotent colony-forming cells, as well as long-term culture initiating cells, at a frequency which is approximately lOO-fold lower than that measured in normal bone marrow [ 11. Cancer therapy with selected myelotoxic drugs induces a period of cytopenia of variable duration followed by rapid haematopoietic recovery. It has been demonstrated that haematopoietic progenitors increase in peripheral blood at the time of haematopoietic recovery which follows drug-induced cytopenia [Z]. Treatment with clinically available haematopoietic growth factors, most notably recombinant human granulocyte colonystimulating factor (rHuG-CSF) and recombinant human granulocyte-macrophage colony-stimulating factor (rHuGMCSF), has been utilised to abbreviate the period of cytopenia after cancer therapy, delivered either at conventional or at high doses [ 3, 41. Investigators have observed that while ameliorating myelotoxicity, growth factor treatment after chemotherapy is able to appreciably increase the number of haematopoietic progenitors circulating in peripheral blood. In addition, a shortterm (i.e. 5-10 days) treatment with the same growth factors, of patients not previously treated with cancer therapy, is able per se to increase the circulation of haematopoietic progenitors. Autologous bone marrow transplantation is a new treatment modality which allows dose escalation of selected cancer drugs without the limitations of haematopoietic toxicity. Both rHuGCSF and rHuGM-CSF have been shown to convincingly accelerate neutrophil recovery following high-dose chemotherapy and autologous bone marrow support [5-71. Despite the use of rHuG-CSF or rHuGM-CSF after transplantation, however, a