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

Citation
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
Citations number
32
Categorie Soggetti
Hematology
Journal title
BloodACNP
ISSN journal
00064971
Volume
85
Issue
9
Year of publication
1995
Pages
2619 - 2626
Database
ISI
SICI code
0006-4971(1995)85:9<2619:PP(CDS>2.0.ZU;2-#
Abstract
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.