Efficacy and cost-benefit analysis of risk-adaptive use of plerixafor for autologous hematopoietic progenitor cell mobilization.

BACKGROUND: Plerixafor (P) reduces mobilization failure rates but it is very expensive. For better utilization of P, we employed a risk-adaptive strategy of using it only in patients who are at high risk of mobilization failure, defined by peripheral blood (PB) CD34+ cell count of fewer than 10×10(6)/L after 4 days of filgrastim (F) alone. STUDY DESIGN AND METHODS: Herein, we present the results of efficacy and cost-benefit analysis of this risk-adaptive approach for hematopoietic progenitor cell (HPC) collection. All patients received daily F for 4 days, and P was added for those "at-risk" patients from Day 4 with apheresis commencing the following morning. F and P were continued daily for up to a maximum of 4 days or until more than 5×10(6) CD34+ cells/kg were collected. Forty-two transplant-eligible patients underwent HPC mobilization. RESULTS: Eighteen patients mobilized with F alone and 24 patients required P with F. Two patients failed adequate HPC mobilization after F+P. Addition of P increased the PB CD34+ count by 6.8-fold with a mean yield of 4.9×10(6) CD34+ cells/kg. Decision-analysis model estimated cost-effectiveness for this risk-adaptive approach of using P with savings of $19,300/patient. Engraftment after HPC infusion was similar among the patients regardless of mobilization regimens. CONCLUSION: These results suggest that addition of P to F based on a risk-adaptive strategy significantly reduces the frequency of mobilization failures and is also cost-effective.

Evaluation of mobilized peripheral blood CD34(+) cells from patients with severe coronary artery disease as a source of endothelial progenitor cells.

BACKGROUND AIMS: The distinction between hematopoietic stem cells (HSC) and endothelial progenitor cells (EPC) is poorly defined. Co-expression of CD34 antigen with vascular endothelial growth factor (VEGF) receptor (VEGFR2) is currently used to define EPC ( 1 ). METHODS: We evaluated the phenotypic and genomic characteristics of peripheral blood-derived CD34(+) cells in 22 granulocyte-colony-stimulating factor (G-CSF)-mobilized patients with severe coronary artery disease and assessed the influence of cell selection and storage on CD34(+) cell characteristics. RESULTS: The median CD34(+) cell contents in the products before and after enrichment with the Isolex 300i Magnetic Cell Selection System were 0.2% and 82.5%, respectively. Cell-cycle analysis showed that 80% of CD34(+) cells were in G0 stage; 70% of the isolated CD34(+) cells co-expressed CD133, a marker for more immature progenitors. However, less than 5% of the isolated CD34(+) cells co-expressed the notch receptor Jagged-1 (CD339) and only 2% of the isolated CD34(+) population were positive for VEGFR2 (CD309). Molecular assessment of the isolated CD34(+) cells demonstrated extremely low expression of VEGFR2 and endothelial nitric oxide synthase (eNOS) and high expression of VEGF-A. Overnight storage at 4 degrees C did not significantly affect CD34(+) cell counts and viability. Storage in liquid nitrogen for 7 weeks did not affect the percentage of CD34(+) cells but was associated with a 26% drop in cell viability. CONCLUSIONS: We have demonstrated that the majority of isolated CD34(+) cells consist of immature and quiescent cells that lack prototypic markers of EPC. High VEGF-A gene expression might be one of the mechanisms for CD34(+) cell-induced angiogenesis.