Colony stimulating factors.

Abstract

The genes for a number of growth factors that stimulate human hematopoietic and lymphoid cells in vitro have recently been cloned and recombinant molecules provided for clinical trials. For three of these (erythropoietin, G-CSF, and GM-CSF), phase I and II studies have been completed and promising results have been obtained. Of particular relevance to the field of bone marrow transplantation (BMT) has been the finding that G-CSF and GM-CSF could shorten the period of neutropenia in patients treated with chemotherapy, including regimens requiring BMT support. Doses of up to 240 micrograms/m2 of GM-CSF have been well tolerated and have increased the peripheral blood neutrophil count in a dose-dependent manner. At higher doses, eosinophils and monocytes were also increased. A continuous infusion over at least 2 h was found to be superior to bolus administration in terms of both efficacy and reduced side effects. These have usually been mild, but bone pain, headache, fatigue and elevated temperature have been encountered. The rise in neutrophil numbers shortly after initiating treatment with GM-CSF is probably due to neutrophil demargination. After a few days increased bone marrow cellularity has also been noted. In addition to these effects on cell numbers, enhancement of granulocyte and monocyte functions has been documented. However, a major concern with the use of G-CSF and GM-CSF in cancer patients, particularly those with hematopoietic malignancies, is the potential of these molecules to stimulate malignant cells.(ABSTRACT TRUNCATED AT 250 WORDS)