Recombinant human granulocyte colony-stimulating factor increases
circulating burst forming unit-erythron and red blood cell production in
patients with severe human immunodeficiency virus infection
SA Miles, RT Mitsuyasu, K Lee, J Moreno, K Alton, JC Egrie, L Souza and JA Glaspy
Division of Hematology-Oncology, University of California, Los Angeles
School of Medicine 90024-1793.
Erythropoietin (EPO) is a major regulatory factor controlling red blood
cell (RBC) production in humans. Although other humoral factors can alter
the proliferation of committed early erythroid progenitors in vitro, no
factor other than EPO has been clearly shown to induce proliferation of
these cells in vivo. In a clinical trail of recombinant granulocyte
colony-stimulating factor (G-CSF) and recombinant EPO in patients with
advanced human immunodeficiency virus (HIV) infection, we noted
reticulocytosis and increases in hemoglobin when G-CSF was administered
before the administration of EPO. Subsequent studies demonstrated a
significant increase in circulating burst forming unit-erythron (BFU-E)
during daily recombinant G-CSF therapy. This increase was both time- and
dose-dependent. The magnitude of increase in BFU-E correlated with the
magnitude of increase in neutrophils and was associated with a mean
increase in reticulocytes of 32,363/microL and a significant increase in
mean hemoglobin of 1.04 +/- 0.34 g/dL over an 18-day interval. There was a
significant increase in iron binding capacity and decreases in iron
saturation and ferritin levels. In patients who were not recently
transfused, there was an associated fall in endogenous erythropoietin
levels. The increase in RBC production was most marked in patients who were
severely anemic, transfusion-dependent, and who had elevated pretreatment
EPO levels. There was no correlation between the increase in BFU-E and
endogenous EPO levels or the time since last dose of zidovudine. The
addition of recombinant EPO therapy three times weekly to patients did not
result in further significant increases in BFU-E but did significantly
increase hemoglobin. Our data suggest that recombinant G-CSF may be one of
the hematopoietic factors that influences production of BFU-E and RBCs in
humans.
Volume 75,
Issue 11,
pp. 2137-2142,
06/01/1990
Copyright © 1990 by The American Society of Hematology
