BLOOD-DERIVED AUTOGRAFTS COLLECTED DURING GRANULOCYTE-COLONY-STIMULATING FACTOR-ENHANCED RECOVERY ARE ENRICHED WITH EARLY THY-1(+) HEMATOPOIETIC PROGENITOR CELLS
R. Haas et al., BLOOD-DERIVED AUTOGRAFTS COLLECTED DURING GRANULOCYTE-COLONY-STIMULATING FACTOR-ENHANCED RECOVERY ARE ENRICHED WITH EARLY THY-1(+) HEMATOPOIETIC PROGENITOR CELLS, Blood, 85(7), 1995, pp. 1936-1943
It was the objective of the study to characterize CD34(+) hematopoieti
c progenitor cells from peripheral blood (PB) and bone marrow (BM) in
a group of 24 cancer patients. After cytotoxic chemotherapy, R-metHu g
ranulocyte colony-stimulating factor (R-metHuG-CSF; filgrastim, 300 mu
g daily, subcutaneously) was given to shorten the time of neutropenia
as well as to increase the rebound of peripheral blood progenitor cel
ls (PBPC) for harvesting. The proportion of CD34(+) cells in the leuka
pheresis products (LPs) was 1.4-fold greater than in BM samples that w
ere obtained at the same day (LP: median, 1.4% v BM: median, 1.0%, P <
.01). Two- and three-color immunofluorescence showed that blood-deriv
ed CD34(+) cells comprised a greater proportion of a particular early
progenitor cell than CD34(+) cells of bone marrow. Blood-derived proge
nitor cells tended to have a higher mean fluorescence intensity of CD3
4 and expressed significantly lower levels of HLA-DR (mean fluorescenc
e intensity of HLA-DR: 442.6 +/- 44.9 [LP] v 661.5 +/- 64.6 [BM], mean
+/- SEM, P < .01). Furthermore, the blood-derived CD34(+) cells compr
ised a 1.7-fold greater proportion of Thy-1(+) cells (LP: median, 24.4
% v BM: median, 14.4%, P < .001) and expressed significantly less c-ki
t (LP: median, 20.5% v BM: median, 31.0%, P < .01). Three-color analys
is showed that high levels of Thy-1 expression were restricted to CD34
(+)/HLA-DR(dim) Or CD34(+)/HLA(-)DR(-) cells confirming the early deve
lopmental stage of this progenitor cell subset. The proportion of CD34
(+)/CD45RA(bright) cells representing late colony-forming unit granulo
cyte-macrophage (CFU-GM) was smaller in LPs compared with BM (P < .05)
. For an examination of BM CD34(+) cells before the mobilization chemo
therapy, samples of 16 patients were available. The mean proportion of
c-kit expressing CD34(+) cells in the bone marrow during G-CSF-stimul
ated reconstitution decreased 1.8-fold compared with baseline values.
There was no difference in the proportion of BM-derived CD34(+)/Thy-1(
+) cells and CD34(+)/CD45RA(+) cells between steady-state hematopoiesi
s and G-CSF-supported recovery. Our data suggest that during G-CSF-enh
anced recovery, CD34(+) cells in the PB are enriched with more primiti
ve progenitor cells to evenly replenish the BM after the chemotherapy-
related cytotoxic damage. (C) 1995 by The American Society of Hematolo
gy.