The effect of recombinant human colony-stimulating factors on hematopoietic reconstitution following autologous bone marrow transplantation

Abstract

The prolonged and severe myelosuppression associated with high-dose chemotherapy and autologous bone marrow transplantation is a major causative factor in patient morbidity and mortality resulting from infection and other causes. The recent molecular cloning, in vitro expression, and formulation of recombinant human colony-stimulating factors (CSF) offered the possibility of reducing the duration of myelosuppression following high-dose chemotherapy and autologous bone marrow transplantation. We have evaluated both recombinant human granulocyte macrophage colony-stimulating factor (GM-CSF) and recombinant human granulocyte colony-stimulating factor (G-CSF) in patients undergoing high-dose combination alkylating-agent therapy with cyclophosphamide, cisplatin, and carmustine (BCNU), and autologous bone marrow transplantation. At clinically acceptable doses, both agents will accelerate hematopoietic recovery and are associated with a reduction in the frequency of bacteremias encountered compared with historical controls. Differences in the pattern of toxicity associated with colony-stimulating factor use, as well as effects on the functional capacity of neutrophils, were noted.