M. Misaki et al., TIMING OF RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR ADMINISTRATION ON NEUTROPENIA INDUCED BY CYCLOPHOSPHAMIDE IN NORMAL MICE, British Journal of Cancer, 77(6), 1998, pp. 884-889
The effects of altering the timing of recombinant human granulocyte co
lony-stimulating factor (rhG-CSF) administration on neutropenia induce
d by cyclophosphamide (CPA) were studied experimentally in a mouse mod
el. Experimental mice were divided into three groups: (a) treatment wi
th rhG-CSF after CPA administration (post-treatment group); (b) treatm
ent with rhG-CSF both before and after CPA administration (pre- and po
st-treatment group); and (c) treatment with saline after CPA administr
ation (control group). The results were as follows. Mice receiving rhG
-CSF on the 2 days preceding CPA treatment, in which progenitor cell c
ounts outside the S-phase when CPA was administered were the lowest of
all the groups, showed accelerated neutrophil recovery but decreased
neutrophil nadirs compared with the control group despite rhG-CSF trea
tment. The pre- and post-treatment group, consisting of mice who recei
ved rhG-CSF treatment on days -4 and -3 before CPA treatment, and in w
hich progenitor cell counts when CPA was administered were increased t
o greater levels than in the other groups, showed remarkably accelerat
ed neutrophil recovery and the greatest increase in the neutrophil nad
irs of all the groups. These results suggested that the kinetics of pr
ogenitor cell populations when chemotherapeutic agents were administer
ed seemed to play an important role in neutropenia after chemotherapy,
and that not only peripheral neutrophil cell and total progenitor cel
l counts but also progenitor cell kinetics should be taken into consid
eration when administering rhG-CSF treatment against the effects of ch
emotherapy.