Subcutaneous recombinant granulocyte-macrophage colony-stimulating factor
used as a single agent and in an alternating regimen with azidothymidine in
leukopenic patients with severe human immunodeficiency virus infection [see
comments]
JM Pluda, R Yarchoan, PD Smith, N McAtee, LE Shay, D Oette, M Maha, SM Wahl, CE Myers and S Broder
Clinical Oncology Program, National Cancer Institute, Bethesda, MD 20892.
We investigated the effects of recombinant human granulocyte-macrophage
colony-stimulating factor (rGM-CSF) administered by the subcutaneous route,
first alone and then alternating with azidothymidine (AZT), in leukopenic
patients with severe human immunodeficiency virus (HIV) infection. Ten
patients with acquired immunodeficiency syndrome (AIDS) or related
disorders, five of whom could not tolerate conventional doses of AZT, were
administered rGM-CSF subcutaneously for 12 days. They then were
administered an alternating regimen using AZT for 1 week, followed by 5
days of subcutaneous rGM-CSF and 2 days without any medication. During the
initial 12 days of GM-CSF administration, there was an increase in the mean
white blood cell (WBC) value. In addition, rGM-CSF stimulated circulating
monocytes as evidenced by an increase in superoxide anion production and
expression of surface HLA-DR antigen. However, at the same time rGM-CSF
increased the serum HIV p24 antigen in each of the six evaluable patients
from 189 x/divided by 2.02 pg/mL (geometric mean x/divided by SEM) at entry
to 375 x/divided by 2.11 pg/mL (P less than .05). During the subsequent
period of alternating AZT and rGM-CSF treatment, serum HIV p24 antigen fell
below the day 14 value in most patients, particularly after the weeks of
AZT administration. The mean T4 cell value increased in patients who had
not previously received AZT, but generally did not change in those who had
prior AZT exposure. Hematologic toxicity appeared to be somewhat reduced
compared with continuous full-dose AZT therapy, and two patients with
previous AZT hematologic toxicity tolerated this alternating regimen for 25
weeks. Additional regimens simultaneously combining these two agents are
worth exploring.
Volume 76,
Issue 3,
pp. 463-472,
08/01/1990
Copyright © 1990 by The American Society of Hematology
