Hematologic effects of recombinant human granulocyte colony-stimulating factor in patients with malignancy

Abstract

The effect of recombinant human granulocyte colony-stimulating factor (G-CSF) on hematologic parameters was evaluated in a phase I clinical study in 18 patients with advanced malignancy. G-CSF was administered once daily as a 30-minute infusion for 14 days; three patients each were treated at increasing dose levels of 1, 3, 10, 30, and 60 micrograms kg-1 day-1. A transient decrease in neutrophil and monocyte counts was observed immediately after the G-CSF infusion, followed by a dose-dependent increase of up to 15-fold. G-CSF-induced neutrophils exhibited an increased O2- radical production, and serum levels of enzymes related to granulocyte turnover, including lysozyme and elastase, were markedly elevated during therapy. A dose-dependent depression of platelet counts occurred in the second third of the treatment course, followed by a spontaneous recovery despite continuing therapy. G-CSF was well-tolerated; minor to moderate bone pain was the most common side effect. The primary course of the malignant diseases studied was not significantly altered. G-CSF appears to be an appropriate means to selectively increase the number of functionally competent polymorphonuclear phagocytes.

Serum levels of granulocyte‐colony stimulating factor (G‐CSF) in bacterial and viral infections, and in atypical pneumonia

“…The lack of correlation between levels of G-CSF and counts of neutrophils and white blood cells in bacterial infections is in accordance with previous studies (Kawakami et al 1990) and the fact that in patients with malignancies the peripheral neutrophilic count changed 4-5 h after G-CSF administration (Lindemann et al, 1989). These findings suggest the possibility that G-CSF regulates mainly neutrophils in the peripheral circulation.…”

In vivo stimulation of neutrophil function by lenograstim (glycosylated rHug‐CSF) in oncohematologic patients: Results of a phase I trial

“…OAlphaMed Press 1066-5099/94/$5.00/0 progenitors. In vivo rHuG-CSF has been reported to induce rapid neutrophilia in a dose dependent fashion [ 11. In spontaneous or chemotherapyinduced neutropenia rHuG-CSF is efficient in reducing the duration and severity of neutropenia and associated morbidity with excellent tolerance either in sequential or chronic administration [2,3]. Not surprisingly, rHuG-CSF has also been found to induce neutrophilia in non-neutropenic hosts [4].…”

Differential effects of granulocyte‐ and granulocyte‐macrophage colony‐stimulating factors (G‐ and GM‐CSF) on neutrophil adhesion in vitro and in vivo

“…When administered in vivo, Gand GM-CSF cause an immediate transient leucopenia (29,30), associated with an in vivo rise in the surface expression of CDI lbjCD18 on circulating neutrophils and monocytes (18, 3 1). Studies using radiolabelled cells have shown that the fall in peripheral counts is associated with the retention of cells in the lungs (1 s), and this has been confirmed histologically in an animal model, in which, 30 min following an intravenous bolus injection of GM-CSF (2 pglkg), leucocytes are seen to marginate within the pulmonary microcirculation, adhering to the pulmonary vascular endothelium (27).…”