Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Hematopoietic Cell Collection

Plerixafor plus pegfilgrastim is a safe, effective mobilization regimen for poor or adequate mobilizers of hematopoietic stem and progenitor cells: a phase I clinical trial

Subjects

Abstract

The safety, kinetics and efficacy of plerixafor+pegfilgrastim for hematopoietic stem and progenitor cell (HSPC) mobilization are poorly understood. We treated 12 study patients (SP; lymphoma n=10 or myeloma n=2) with pegfilgrastim (6 mg SC stat D1) and plerixafor (0.24 mg/kg SC nocte from D3). Six SP were ‘predicted poor-mobilizers’ and six were ‘predicted adequate-mobilizers’. Peripheral blood (PB) CD34+ monitoring commenced on D3. Apheresis commenced on D4. Comparison was with 22 historical controls (HC; lymphoma n=18, myeloma n=4; poor mobilizers n=4), mobilized with pegfilgrastim alone. Eight (67%) SP had PB CD34+ count 5 × 106/L D3 post pegfilgrastim; all SP surpassed this threshold the morning after plerixafor. In SP, PBCD34+ counts peaked D4 6/12 (50%), remaining 5 × 106/L for 4 days in 8/12 (67%). All SP successfully yielded target cell numbers (2 × 106/kg) within four aphereses. After maximum four aphereses, median total CD34+ yield was higher in SP than HC; 8.0 (range 2.4–12.9) vs 4.8 (0.4–14.0) × 106/kg (P=0.04). Seven of twelve (58%) SP achieved target yield after one apheresis. Flow cytometry revealed no tumor cells in PB or apheresis product of SP. Plerixafor+pegfilgrastim was well tolerated with bone pain (n=2), diarrhoea (n=2) and facial paraesthesiae (n=3). Plerixafor+pegfilgrastim is a simple, safe and effective HSPC mobilization regimen in myeloma and lymphoma, in both poor and good mobilizers, and is superior to pegfilgrastim alone.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Harousseau JL, Attal M, Divine M, Milpied N, Marit G, Leblond V et al. Comparison of autologous bone marrow transplantation and peripheral blood stem cell transplantation after first remission induction treatment in multiple myeloma. Bone Marrow Transplant 1995; 15: 963–969.

    CAS  PubMed  Google Scholar 

  2. To LB, Roberts MM, Haylock DN, Dyson PG, Branford AL, Thorp D et al. Comparison of haematological recovery times and supportive care requirements of autologous recovery phase peripheral blood stem cell transplants, autologous bone marrow transplants and allogeneic bone marrow transplants. Bone Marrow Transplant 1992; 9: 277–284.

    CAS  PubMed  Google Scholar 

  3. Koc ON, Gerson SL, Cooper BW, Laughlin M, Meyerson H, Kutteh L et al. Randomized cross-over trial of progenitor-cell mobilization: high-dose cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) versus granulocyte-macrophage colony-stimulating factor plus G-CSF. J Clin Oncol 2000; 18: 1824–1830.

    Article  CAS  PubMed  Google Scholar 

  4. Demirer T, Buckner CD, Gooley T, Appelbaum FR, Rowley S, Chauncey T et al. Factors influencing collection of peripheral blood stem cells in patients with multiple myeloma. Bone Marrow Transplant 1996; 17: 937–941.

    CAS  PubMed  Google Scholar 

  5. Desikan KR, Barlogie B, Jagannath S, Vesole DH, Siegel D, Fassas A et al. Comparable engraftment kinetics following peripheral-blood stem-cell infusion mobilized with granulocyte colony-stimulating factor with or without cyclophosphamide in multiple myeloma. J Clin Oncol 1998; 16: 1547–1553.

    Article  CAS  PubMed  Google Scholar 

  6. Rettig MP, Ramirez P, Nervi B, DiPersio JF . CXCR4 and mobilization of hematopoietic precursors. Methods Enzymol 2009; 460: 57–90.

    Article  CAS  PubMed  Google Scholar 

  7. Broxmeyer HE, Orschell CM, Clapp DW, Hangoc G, Cooper S, Plett PA et al. Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. J Exp Med 2005; 201: 1307–1318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Douglas S, Smith C, McFarland R, Badel K, Calandra G . AMD3100 with G-CSF for autologous peripheral blood progenitor cell (PBPC) mobilization in non-hodgkin’s lymphoma (NHL) and multiple myeloma (MM): mobilization, engraftment, and pharmacokinetics (PK). Blood ASH Annual Meeting Abstracts 2006; 108: 3383.

    Google Scholar 

  9. Ehninger G, Fruehauf S, Hubel K, Platzbecker U, Badel K, Calandra G . Steady state mobilization of autologous blood stem cells using G-CSF and AMD3100 in patients with multiple myeloma (MM). Blood ASH Annual Meeting Abstracts 2006; 108: 5219.

    Google Scholar 

  10. Flomenberg N, Devine SM, DiPersio JF, Liesveld JL, McCarty JM, Rowley SD et al. The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone. Blood 2005; 106: 1867–1874.

    Article  CAS  PubMed  Google Scholar 

  11. DiPersio JF, Micallef IN, Stiff PJ, Bolwell BJ, Maziarz RT, Jacobsen E et al. Phase III prospective randomized double-blind placebo-controlled trial of plerixafor plus granulocyte colony-stimulating factor compared with placebo plus granulocyte colony-stimulating factor for autologous stem-cell mobilization and transplantation for patients with non-Hodgkin’s lymphoma. J Clin Oncol 2009; 27: 4767–4773.

    Article  CAS  PubMed  Google Scholar 

  12. DiPersio JF, Stadtmauer EA, Nademanee A, Micallef IN, Stiff PJ, Kaufman JL et al. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood 2009; 113: 5720–5726.

    CAS  PubMed  Google Scholar 

  13. Gaugler B, Arbez J, Legouill S, Tiberghien P, Moreau P, Derenne S et al. Characterization of peripheral blood stem cell grafts mobilized by granulocyte colony-stimulating factor and plerixafor compared with granulocyte colony-stimulating factor alone. Cytotherapy 2013; 15: 861–868.

    Article  CAS  PubMed  Google Scholar 

  14. Biganzoli L, Untch M, Skacel T, Pico JL . Neulasta (pegfilgrastim): a once-per-cycle option for the management of chemotherapy-induced neutropenia. Semin Oncol 2004; 31 (3 Suppl 8): 27–34.

    Article  CAS  PubMed  Google Scholar 

  15. Steidl U, Fenk R, Bruns I, Neumann F, Kondakci M, Hoyer B et al. Successful transplantation of peripheral blood stem cells mobilized by chemotherapy and a single dose of pegylated G-CSF in patients with multiple myeloma. Bone Marrow Transplant 2005; 35: 33–36.

    Article  CAS  PubMed  Google Scholar 

  16. Bruns I, Steidl U, Kronenwett R, Fenk R, Graef T, Rohr UP et al. A single dose of 6 or 12mg of pegfilgrastim for peripheral blood progenitor cell mobilization results in similar yields of CD34+ progenitors in patients with multiple myeloma. Transfusion 2006; 46: 180–185.

    Article  CAS  PubMed  Google Scholar 

  17. Molineux G, Kinstler O, Briddell B, Hartley C, McElroy P, Kerzic P et al. A new form of Filgrastim with sustained duration in vivo and enhanced ability to mobilize PBPC in both mice and humans. Exp Hematol 1999; 27: 1724–1734.

    Article  CAS  PubMed  Google Scholar 

  18. Kroschinsky F, Holig K, Poppe-Thiede K, Zimmer K, Ordemann R, Blechschmidt M et al. Single-dose pegfilgrastim for the mobilization of allogeneic CD34+ peripheral blood progenitor cells in healthy family and unrelated donors. Haematologica 2005; 90: 1665–1671.

    CAS  PubMed  Google Scholar 

  19. Hosing C, Qazilbash MH, Kebriaei P, Giralt S, Davis MS, Rhodes B et al. Fixed-dose single agent pegfilgrastim for peripheral blood progenitor cell mobilization in patients with multiple myeloma (MM). Blood ASH Annual Meeting Abstracts 2005; 106: 2923.

    Google Scholar 

  20. Herbert KE, Gambell P, Link EK, Mouminoglu A, Wall DM, Harrison SJ et al. Pegfilgrastim compared with filgrastim for cytokine-alone mobilization of autologous haematopoietic stem and progenitor cells. Bone Marrow Transplant 2013; 48: 351–356.

    Article  CAS  PubMed  Google Scholar 

  21. Rawstron AC, Orfao A, Beksac M, Bezdickova L, Brooimans RA, Bumbea H et al. Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders. Haematologica 2008; 93: 431–438.

    Article  PubMed  Google Scholar 

  22. Russell N, Douglas K, Ho AD, Mohty M, Carlson K, Ossenkoppele GJ et al. Plerixafor and granulocyte colony-stimulating factor for first-line steady-state autologous peripheral blood stem cell mobilization in lymphoma and multiple myeloma: results of the prospective PREDICT trial. Haematologica 2013; 98: 172–178.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Mohty M, Duarte RF, Croockewit S, Hubel K, Kvalheim G, Russell N . The role of plerixafor in optimizing peripheral blood stem cell mobilization for autologous stem cell transplantation. Leukemia 2011; 25: 1–6.

    Article  CAS  PubMed  Google Scholar 

  24. Kroschinsky F, Holig K, Platzbecker U, Poppe-Thiede K, Ordemann R, Blechschmidt M et al. Efficacy of single-dose pegfilgrastim after chemotherapy for the mobilization of autologous peripheral blood stem cells in patients with malignant lymphoma or multiple myeloma. Transfusion 2006; 46: 1417–1423.

    Article  CAS  PubMed  Google Scholar 

  25. Costa LJ, Miller AN, Alexander ET, Hogan KR, Shabbir M, Schaub C et al. Growth factor and patient-adapted use of plerixafor is superior to CY and growth factor for autologous hematopoietic stem cells mobilization. Bone Marrow Transplant 2011; 46: 523–528.

    Article  CAS  PubMed  Google Scholar 

  26. Costa LJ, Alexander ET, Hogan KR, Schaub C, Fouts TV, Stuart RK . Development and validation of a decision-making algorithm to guide the use of plerixafor for autologous hematopoietic stem cell mobilization. Bone Marrow Transplant 2011; 46: 64–69.

    Article  CAS  PubMed  Google Scholar 

  27. Costa LJ, Kramer C, Hogan KR, Butcher CD, Littleton AL, Shoptaw KB et al. Pegfilgrastim- versus filgrastim-based autologous hematopoietic stem cell mobilization in the setting of preemptive use of plerixafor: efficacy and cost analysis. Transfusion 2012; 52: 2375–2381.

    Article  CAS  PubMed  Google Scholar 

  28. Anwer F, Green M, Yeager AM . Effective primary mobilization of autologous peripheral blood stem cells with granulocyte colony-stimulating factor and plerixafor in lenalidomide-treated patients with multiple myeloma. Blood 2010; 116 abstract 2254.

  29. Schulman KA, Birch R, Zhen B, Pania N, Weaver CH . Effect of CD34(+) cell dose on resource utilization in patients after high-dose chemotherapy with peripheral-blood stem-cell support. J Clin Oncol 1999; 17: 1227.

    Article  CAS  PubMed  Google Scholar 

  30. Grignani G PE, Cavalloni G, Carnevale Schianca F, Aglietta M . Letter to the Editor: clinical use of AMD3100 to mobilize CD34+ cells in patients affected by non-hodgkin’s lymphoma or multiple myeloma. J Clin Oncol 2005; 23: 3871–3872.

    Article  PubMed  Google Scholar 

  31. Liesveld JL, Bechelli J, Rosell K, Lu C, Bridger G, Phillips G 2nd et al. Effects of AMD3100 on transmigration and survival of acute myelogenous leukemia cells. Leuk Res 2007; 31: 1553–1563.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Nervi B, Holt M, Rettig MP, Bridger G, Ley TJ, DiPersio JF . AMD3100 mobilizes acute promyelocytic leukemia cells from the bone marrow into the peripheral blood and sensitizes leukemia cells to chemotherapy. Blood ASH Annual Meeting Abstracts 2005; 106: 246.

    Google Scholar 

  33. Nervi B, Ramirez P, Rettig MP, Uy GL, Holt MS, Ritchey JK et al. Chemosensitization of AML following mobilization by the CXCR4 antagonist AMD3100. Blood 2009; 113: 6206–6214.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Tricot G, Cottler-Fox MH, Calandra G . Safety and efficacy assessment of plerixafor in patients with multiple myeloma proven or predicted to be poor mobilizers, including assessment of tumor cell mobilization. Bone Marrow Transplant 2010; 45: 63–68.

    Article  CAS  PubMed  Google Scholar 

  35. Costa LJ, Alexander ET, Hogan KR, Schaub C, Fouts TV, Stuart RK . Development and validation of a decision-making algorithm to guide the use of plerixafor for autologous hematopoietic stem cell mobilization. Bone Marrow Transplant 2010; 46: 64–69.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to K E Herbert.

Ethics declarations

Competing interests

Dr Herbert was the recipient of a Research Support Grant-In-Aid during from Genzyme during the design and recruitment period of this study.

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Herbert, K., Demosthenous, L., Wiesner, G. et al. Plerixafor plus pegfilgrastim is a safe, effective mobilization regimen for poor or adequate mobilizers of hematopoietic stem and progenitor cells: a phase I clinical trial. Bone Marrow Transplant 49, 1056–1062 (2014). https://doi.org/10.1038/bmt.2014.112

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2014.112

This article is cited by

Search

Quick links