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Potentiation of granulocyte colony-stimulating factor-induced mobilization
of circulating progenitor cells by seven-day pretreatment with
interleukin-3
K Geissler, C Peschel, D Niederwieser, H Strobl, J Goldschmitt, L Ohler, P Bettelheim, P Kahls, C Huber, K Lechner, P Hocker and K Kolbe
Blood Transfusion Service, Institute of Immunology, University of Vienna,
Austria.
Granulocyte colony-stimulating factor (G-CSF) as a single agent is
increasingly used for the mobilization of peripheral blood progenitor cells
(PBPCs) for stem cell transplantation. In patients with perturbed
hematopoiesis the mobilizing capacity of G-CSF alone may be inadequate. We
have shown in rhesus monkeys that interleukin-3 (IL-3) pretreatment
markedly potentiated the increase in PBPC numbers by subsequent
administration of granulocyte/macrophage-CSF (GM-CSF). Here we studied the
effect of IL-3 pretreatment on G-CSF-induced mobilization of PBPCs in 6
patients with Hodgkin's disease (n = 5) or non-Hodgkin's lymphoma (n = 1)
who had low progenitor cell numbers because of previous chemotherapy.
Patients were treated in cycle 1 with G-CSF at a dose of 5 microgram/kg/d
for 5 days and, after a treatment-free interval, received cycle 2
consisting of 5 microgram/kg/d of IL-3 for 7 days followed by G-CSF again
at a dose of 5 microgram/kg/d for 5 days. G-CSF alone increased the mean
number of circulating colony-forming units-GM (CFU-GM) by 21-fold, the
number of burst-forming units-erythroid (BFU- E) by 9-fold, and the number
of CFU-mix by 24-fold over pretreatment values. Treatment with 5
microgram/kg/d of IL-3 for 7 days did not mobilize by itself but
significantly potentiated G-CSF-induced mobilization of all progenitor cell
types leading to a 56-, 15-, and 46- fold increase over baseline of CFU-GM,
BFU-E, and CFU-mix numbers, respectively. In 2 patients in whom
leukapheresis was performed after G- CSF alone the target number of 2 x
10(6)/kg CD34+ cells was not reached. However, leukapheresis after the
IL-3/G-CSF combination obtained > or =2 x 10(6)/kg CD34+ cells in 3 of 6
patients, including both patients who had inadequate collection after G-CSF
alone. In one patient adequate function of mobilized progenitors could be
shown by the demonstration of rapid trilineage engraftment after infusion
of progenitors after myeloablative chemotherapy. Seven-day pretreatment
with IL-3 may be a useful mean to augment mobilization of circulating
progenitors by G-CSF. The combination of IL-3 and G-CSF seems to allow the
procurement of sufficient numbers of PBPCs in some patients who cannot be
mobilized adequately by G-CSF alone.
Volume 87,
Issue 7,
pp. 2732-2739,
04/01/1996
Copyright © 1996 by The American Society of Hematology
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