Effect of recombinant human granulocyte-macrophage colony-stimulating factor on myelopoiesis in patients with refractory metastatic carcinoma

The effect of human recombinant GM-colony-stimulating factor (CSF) was evaluated in ten patients with refractory metastatic carcinoma. Initially they received an intravenous (IV) bolus injection of 5 or 25 micrograms/m2 for assessment of acute responses. Six days later, continuous IV infusions of 100 or 500 micrograms/m2 were initiated for a 14-day treatment course. All patients developed profound leukopenia within five to 30 minutes of the bolus injection. This appeared to result from increased expression of an adhesion-promoting glycoprotein (GP) on neutrophils and monocytes as judged by increased reactivity to the Mo1 monoclonal antibody (MoAb). Leukocyte counts returned to normal levels within two hours as cells were released from marrow stores. With the continuous infusion, leukocyte counts increased by 24 hours; peak values of 22,960 and 75.900/microL were achieved after ten to 14 days of treatment with the two dose levels of GM-CSF. This leukocytosis was due to an increase in virtually all cell types. At the high dose level, there was a striking increase in neutrophils (49,400/microL) and eosinophils (20,905/microL) with a sixfold increase in monocytes and two- to threefold increase in lymphocytes. Leukocyte counts declined promptly after cessation of the infusion but remained above baseline for as long as 2 weeks in some patients. These results suggest that GM- CSF may be useful as an adjuvant therapy by stimulating myelopoiesis in cancer patients.