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 [see comments]

Abstract

Peripheral blood progenitor cells (PBPC) can be mobilized using cytotoxic 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 and 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 patients (four with high-grade non-Hodgkin's lymphoma [NHL], two with low-grade NHL, two with Hodgkin's disease, two with multiple myeloma, three with breast cancer, one with ovarian cancer, and one with germ cell tumor) were included in this study. The comparison of immunofluorescence 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 expression, 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 probability 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 threshold-dose of progenitor cells required for rapid and sustained engraftment after high-dose therapy. For the total steady-state BM CD34+ cell population, a weak correlation (r = .57, P < .05) with the mobilized CD34+ cells only became apparent when an outlier was removed from the analysis. Neither the CD34+ immunologic subgroups defined by the coexpression of the myeloid lineage-associated antigens CD33 or CD45-RA or the phenotypically primitive CD34+/HLA-DR-subset nor the BM 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 circulate. Our results permit us to recognize patients who are at risk to collect low numbers of progenitor cells and those who are likely to achieve sufficient or high progenitor cell yields even before mobilization chemotherapy is administered.

Delineation of Cell Cycle State and Correlation to Adhesion Molecule Expression of Human CD34+Cells from Steady‐State Bone Marrow and Peripheral Blood Mobilized Following G‐CSF‐Supported Chemotherapy

“…After immunomagnetic CD34 + cell selection, the percentage of CD34 + cells in BM was 89.18% ± 3.17% and 91.05% ± 2.26% in LP samples. When we analyzed the coexpression on CD34 + cells of the lineage-associated and maturation-associated antigens CD7, CD19, CD33, CD38, CD45RA, CDw90, CD117, and HLA-DR as well as the activation molecule CD71, we found that greater than 95% of hematopoietic cells in both compartments coexpressed the HLA-DR and CD38 antigens, whereas in LP compared to BM, the proportion of phenotypically primitive CD34 + /CDw90 + cells and of myeloid precursors (i.e., CD34 + /CD33 + ) was significantly greater at the expense of B-lymphocyte precursors (CD34 + /CD19 + ), as already reported [28,29] (data not shown).…”

Peripheral blood progenitor cell (PBPC) counts during steady‐state haemopoiesis enable the estimation of the yield of mobilized PBPC after granulocyte colony‐stimulating factor supported cytotoxic chemotherapy: an update on 100 patients

“…Our initial report on the predictive value of steady-state PB CD34 þ cell counts for the PBPC yield after mobilization with chemotherapy and G-CSF or G-CSF alone has been confirmed by other groups (Fruehauf et al, 1995;Brown et al, 1996;Husson et al, 1996;Haug et al, 1997). The present study on a large number of patients allowed an assessment of the determinants of premobilization progenitor cell levels and PBPC mobilization in different disease entities.…”

“…᭧ 1999 Blackwell Science Ltd, British Journal of Haematology 105: [786][787][788][789][790][791][792][793][794] G-CSF-supported chemotherapy (Fruehauf et al, 1995;Haug et al, 1997) or G-CSF mobilization alone (Husson et al, 1996;Brown et al, 1996). In this trial we have studied the possible determinants, such as previous therapy, on the steady-state CD34 þ cell levels.…”

Progenitor cell yield in sequential blood stem cell mobilization in the same patients: insights into chemotherapy dose escalation and combination of haemopoietic growth factor and chemotherapy

“…The efficacy of different mobilization strategies and the quality of the mobilized products are now subjects under intensive study. The dose of myelosuppressive chemotherapy (Kotasek et al, 1992;Rowlings et al, 1992), the addition of haemopoietic growth factors (Siena et al, 1989), bone marrow involvement by underlying disease (Shepherd et al, 1991), prior chemotherapy (To et al, 1990;Haas et al, 1994) and pre-mobilization peripheral blood progenitor level (Fruehauf et al, 1995) are factors which have been proposed as important determinants on the harvest's yield. However, data from randomized prospective studies comparing the efficacy of different mobilization regimens are still lacking.…”