PERIPHERAL-BLOOD PROGENITOR-CELL (PBPC) COUNTS DURING STEADY-STATE HEMATOPOIESIS ALLOW TO ESTIMATE THE YIELD OF MOBILIZED PBPC AFTER FILGRASTIM (R-METHUG-CSF)-SUPPORTED CYTOTOXIC CHEMOTHERAPY
S. Fruehauf et al., PERIPHERAL-BLOOD PROGENITOR-CELL (PBPC) COUNTS DURING STEADY-STATE HEMATOPOIESIS ALLOW TO ESTIMATE THE YIELD OF MOBILIZED PBPC AFTER FILGRASTIM (R-METHUG-CSF)-SUPPORTED CYTOTOXIC CHEMOTHERAPY, Blood, 85(9), 1995, pp. 2619-2626
Peripheral blood progenitor cells (PBPC) can be mobilized using cytoto
xic chemotherapy and cytokines. There is a substantial variability in
the yield of hematopoietic progenitor cells between patients. We were
looking for predictive parameters indicating a patient's response to a
given mobilization regimen. Multiparameter flow-cytometry analysis an
d clonogenic assays were used to examine the hematopoietic progenitor
cells in bone marrow (BM) and peripheral blood (PB) before filgrastim
(R-metHuG-CSF; Amgen, Thousand Oaks, CA)-supported chemotherapy and in
PB and leukapheresis products (LPs) in the recovery phase. Fifteen pa
tients (four with high-grade non-Hodgkin's lymphoma [NHL], two with lo
w-grade NHL, two with Hodgkin's disease, two with multiple myeloma, th
ree with breast cancer, one with ovarian cancer, and one with germ cel
l tumor) were included in this study. The comparison of immunofluoresc
ence plots showed a homogenous population of strongly CD34(+) cells in
steady-state and mobilized PB whereas in steady-state BM, the CD34(+)
cells ranged from strongly positive with continuous transition to the
CD34(-) population. Consistent with the similarity in CD34 antigen ex
pression, a correlation analysis showed steady-state PB CD34(+) cells
(r = .81, P <.001) and colony-forming cells (CFCs; r = .69, P <.01) to
be a measure of a patient's mobilizable CD34(+) cell pool. Individual
estimates of progenitor cell yields could be calculated. With a proba
bility of 95%, eg, 0.4 steady-state PB CD34(+) cells x 10(6)/L allowed
to collect in six LPs 2.5 x 10(6) CD34(+) cells/kg, the reported thre
shold-dose of progenitor cells required for rapid and sustained engraf
tment after high-dose therapy. For the total steady-state BM CD34(+) c
ell population, a weak correlation (r = .57, P < .05) with the mobiliz
ed CD34(+) cells only became apparent when an outlier was removed from
the analysis. Neither the CD34(+) immunologic subgroups defined by th
e coexpression of the myeloid lineage-associated antigens CD33 or CD45
-RA or the phenotypically primitive CD34(+)/HLA-DR(-) subset nor the B
M CFC count had a predictive value for the mobilization outcome. This
may be caused by the additional presence of maturing progenitor cells
in BM, which express lower levels of the CD34 antigen and do not circu
late. Our results permit us to recognize patients who are at risk to c
ollect low numbers of progenitor cells and those who are likely to ach
ieve sufficient or high progenitor cell yields even before mobilizatio
n chemotherapy is administered. (C) 1995 by The American Society of He
matology.