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Effect of recombinant human granulocyte-macrophage colony-stimulating
factor on myelopoiesis in patients with refractory metastatic carcinoma
N Phillips, S Jacobs, R Stoller, M Earle, D Przepiorka and RK Shadduck
Pittsburgh Cancer Institute, University of Pittsburgh, School of Medicine.
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.
Volume 74,
Issue 1,
pp. 26-34,
07/01/1989
Copyright © 1989 by The American Society of Hematology
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