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Conditioning

Leukemia cell mobilization with G-CSF plus plerixafor during busulfan–fludarabine conditioning for allogeneic stem cell transplantation

Bone Marrow Transplantation volume 50, pages 939–946 (2015)Cite this article

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Abstract

We hypothesized that during conditioning chemotherapy for allogeneic stem cell transplant (allo-SCT), the disruption of stromal–leukemia interactions using G-CSF in combination with the CXCR4-specific inhibitor, plerixafor, may promote the release of leukemic cells from the niche and increase tumor elimination. In a phase 1/2 investigation, we treated 45 AML/myelodysplastic syndrome (MDS)/CML patients (34 AML, 7 MDS and 4 CML) with G-CSF (10 μg/kg daily for 6 days starting on day −9) plus plerixafor (doses of 0, 80, 160 or 240 μg/kg daily for 4 days starting on day −7) along with the busulfan–fludarabine (Bu–Flu) conditioning regimen. In the phase 1 part, we determined that G-CSF plus plerixafor is safe in this setting. We compared the clinical effects and outcomes of AML/MDS study patients (n=40) with 164 patients from a historical data set who received Bu–Flu alone before allo-SCT by stratifying on cytogenetics and disease status to correct for bias. Study patients had increased myeloid chimerism and lower rates of GvHD. There was no significant difference in relapse-free survival or overall survival. The G-CSF plus plerixafor combination increased circulating WBCs, CD34+ cells and CXCR4+ cells, and preferentially mobilized FISH+ leukemic cells.

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Acknowledgements

This work was supported by the National Institutes of Health/National Cancer Institute grants P01 CA55164-19, P01 CA049639-21, R21 CA137637 (to MK), CCSG P30 CA016672 and the Paul and Mary Haas Chair in Genetics (to MA). We thank Professor Axel Zander (University Medical Center Hamburg-Eppendorf Clinic for Stem Cell Transplantation, Hamburg, Germany) for scientific input on the manuscript.

Author contributions

MK designed the research, contributed essential tools, performed the research, analyzed the data, wrote the manuscript and funded the studies. CBB performed the research, analyzed the data and wrote the manuscript. PFT and ZZ performed the research and analyzed the data. ES, SC, PK, AA, UP, PA, YN and SP contributed essential tools. WQ, JC, GR, BM, R-YW, HL, WS, GW, AG and R Cool performed the research and analyzed the data. MA and R Champlin designed the research, contributed essential tools and analyzed the data.

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Author notes

  1. M Konopleva and C B Benton: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    M Konopleva, E Shpall, S Ciurea, P Kebriaei, A Alousi, U Popat, P Anderlini, Y Nieto, S Parmar, J Chen, G Rondon, B McMullin, R-Y Wang, H Lu, W Schober, G Woodworth, M Andreeff & R Champlin

  2. Departments of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    M Konopleva, C B Benton, Z Zeng & M Andreeff

  3. Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston,, TX, USA

    P F Thall & W Qiao

  4. Division of Pharmacy, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    A Gulbis & R Cool

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Corresponding author

Correspondence to R Champlin.

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Competing interests

MK and RC received research funding from Genzyme. RC served as a consultant for Genzyme. The remaining authors declare no conflict of interest.

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Konopleva, M., Benton, C., Thall, P. et al. Leukemia cell mobilization with G-CSF plus plerixafor during busulfan–fludarabine conditioning for allogeneic stem cell transplantation. Bone Marrow Transplant 50, 939–946 (2015). https://doi.org/10.1038/bmt.2015.58

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