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Hematopoietic stem cell depletion by restorative growth factor regimens
during repeated high-dose cyclophosphamide therapy [see comments]
RL Hornung and DL Longo
Biological Carcinogenesis & Development Program, Program Resources,
Inc/DynCorp, National Cancer Institute-Frederick Cancer Research &
Development Center 21702-1201.
We studied the effects of six cycles of repeated cyclophosphamide (CTX)
therapy followed by restorative therapy with either granulocyte- macrophage
colony-stimulating factor (GM-CSF) or G-CSF on the hematopoietic stem cell
compartment. Stem cell function was assessed by serially transferring bone
marrow cells from CTX-CSF-treated mice into lethally irradiated recipient
mice. Bone marrow cells from mice that initially received either G-CSF or
GM-CSF after CTX therapy more rapidly lost the ability to repopulate the
recipient lymphoid organs, showed a dramatic loss of hematopoietic
progenitors, a more rapid loss of CFU-S capacity, and a 40% to 50%
reduction in marrow repopulating ability (MRA). Interleukin-1 (IL-1)
appeared to have little effect on the CTX-treated mice when used alone.
However, when administered before the CTX-CSF regimen, IL-1 prevented the
stem cell depletion as determined by CFU-C, CFU-S, and MRA through the
serial transplantation procedures. These results support the hypothesis
that repeated treatments with myelosuppressive drugs followed by
stimulation with the CSFs may induce damage to the host stem cell
compartment, and further suggest that pretreatment with IL-1 before CTX
therapy may prevent this stem cell damage.
Volume 80,
Issue 1,
pp. 77-83,
07/01/1992
Copyright © 1992 by The American Society of Hematology
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