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Recombinant human granulocyte colony-stimulating factor repairs the
abnormalities of neutrophils in patients with myelodysplastic syndromes and
chronic myelogenous leukemia
A Yuo, S Kitagawa, T Okabe, A Urabe, Y Komatsu, S Itoh and F Takaku
We examined the in vitro effect of recombinant human granulocyte colony-
stimulating factor (rhG-CSF) on neutrophil anomalies in 20 patients with
myelodysplastic syndromes (MDS) and eight patients with chronic myelogenous
leukemia (CML). Neutrophil alkaline phosphatase (NAP) activity was
determined in nine MDS patients and eight CML patients by a scoring method.
NAP scores were decreased in six of the nine patients with MDS and in all
of the patients with CML. In all patients with these diseases, NAP scores
increased by incubating the blood with rhG- CSF. An increase in NAP scores
by rhG-CSF was observed even at a concentration of 1 U/mL in patients with
MDS but was observed only at higher concentrations (1,000 to 10,000 U/mL)
in patients with CML. Significant increases in NAP scores occurred at 12
hours' incubation in patients with MDS, whereas the increase was more
gradual in patients with CML. This time course difference was thought to be
due mainly to the difference in cell populations of circulating myeloid
cells between MDS patients and CML patients. Induction of NAP activity by
rhG-CSF in patients with both these diseases was suppressed by the addition
of inhibitors of RNA or protein synthesis. Neutrophil superoxide anion (O2-
) production induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) was
determined in the other 11 patients with MDS. This neutrophil function was
decreased in seven of the 11 patients with MDS, normal in two patients, and
increased in two patients. Preincubation with rhG-CSF caused a significant
increase in fMLP-induced O2- production in nine of the 11 patients with
MDS. rhG-CSF enhanced this neutrophil function in a time- and
dose-dependent manner, and maximal stimulation was observed at 2,000 to
4,000 U/mL of rhG-CSF and at five to ten minutes' incubation. The present
results show that rhG-CSF is able to repair at least in part the neutrophil
anomalies in these patients, and our data, especially for patients with
MDS, suggest the clinical usefulness of rhG-CSF for this preleukemic
disorder.
Volume 70,
Issue 2,
pp. 404-411,
08/01/1987
Copyright © 1987 by The American Society of Hematology

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