A combination of granulocyte-colony-stimulating factor (G-CSF) and plerixafor mobilizes more primitive peripheral blood progenitor cells than G-CSF alone: results of a European phase II study

Abstract

Background aims

Previous studies in xenograft models have shown that human peripheral blood progenitor cells (PBPC) mobilized with the CXCR4 antagonist plerixafor (AMD3100) have a higher bone marrow (BM) reconstitution potential than granulocyte–colony-stimulating factor (G-CSF)-mobilized PBPC.

Methods

PBPC obtained during G-CSF-supported mobilization before and after a supplementary administration of AMD3100 from patients with multiple myeloma and non-Hodgkin's lymphoma (n=15; phase II study) were investigated for co-expression of primitive and lineage-associated markers, their proliferative activity in vitro and repopulation potential after clinical transplantation.

Results

A significant increase in primitive CD34⁺ CD38⁻ cells was observed in intraindividual comparisons of all patients after administration of G-CSF+AMD3100 (peripheral blood: median 8-fold, range 2,4-fold - 39-fold) compared with G-CSF alone. Using a long-term culture-initiating cell assay, this increase was confirmed. After transplantation of G-CSF+AMD3100-mobilized PBPC, the time to leukocyte reconstitution >1×10³/μL and platelet reconstitution >2×10⁴/μL was 14 (10–19 days) and 13 days (10–15 days), respectively. A complete and stable hematologic reconstitution (platelets >1.5×10⁵/μL) was observed in 91% of all patients within 35 days.

Conclusions

An additional application of AMD3100 to a standard G-CSF mobilization regimen leads to a significant increase in primitive PBPC with high repopulation capacity.

Keywords::

• AMD3100
• granulocyte–colony-stimulating factor
• mobilization
• peripheral blood progenitor cells

Acknowledgments

We are grateful for valuable comments by Professor Dr W. J. Zeller, Heidelberg, the expert technical assistance of Mr Bernhard Berkus, Mr Hans-Jürgen Engel and Mrs Sigrid Heil (DKFZ), Mrs Brigitte Geisler and Mrs Katrin Miesalla (Department of Internal Medicine V), as well as the excellent co-ordination of study patient management by Mrs Annette Opgenorth, Mrs Eike John-Spindler and Mrs Marlies Stützle-Schnetz from the study center of the Department of Internal Medicine V, and finally the physicians and nurses of the transplant unit of the Department of Internal Medicine V for their support of the study, as well as Mrs Fara Bozorgmehr, Mr Frank Giordano and Mr Daniel Ribeiro (DKFZ) for their help with sample collection.

Potential conflict of interest declaration: Professor Dr S. Fruehauf has performed contract work for AnorMED; Dr G. Calandra is vice-president ‘clinical research’ at AnorMED. All other authors do not have any potential conflicts of interest.