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:

Stem Cell Procurement

Ancestim (r-metHuSCF) plus filgrastim and/or chemotherapy for mobilization of blood progenitors in 513 poorly mobilizing cancer patients: the French compassionate experience

Bone Marrow Transplantation volume 46, pages 936–942 (2011)Cite this article

Subjects

Abstract

Ancestim (r-MetHuSCF) is available in France for compassionate use in patients who are candidates for high-dose chemotherapy and autologous transplantation, and who failed in previous attempts at mobilization and collection. We report here data from 513 adult patients who benefited from this program, between January 1998 and July 2007. Given with systematic premedication, ancestim was generally well tolerated, although severe but not life-threatening adverse events were reported in 12 individuals. Overall, a graft was obtained or completed for 235 patients (46%). The median number of collected CD34+ cells was 3.00 × 106/kg (range: 0.03–39.50). The target threshold of 2 × 106 CD34+ cells/kg was reached in 161 patients (31%). Factors associated with collection were diagnosis of myeloma, no previous autologous transplant, no more than one previous failed attempt and a mobilization regimen including cytotoxic agents. A total of 207 patients (40%) proceeded to high-dose chemotherapy and autologous transplantation. The median time to reach 0.5 × 109/L neutrophils and 20 × 109/L platelets was 12 (6–40) and 13 (0–31) days, respectively. We conclude that a combination of ancestim with filgrastim successfully mobilized CD34+ cells in peripheral blood, and allowed adequate collection in preparation for autologous transplantation in approximately one-third of poorly mobilizing patients.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1

Similar content being viewed by others

References

  1. Gratwohl A, Baldomero H, Frauendorfer K, Niederwieser D . Why are there regional differences in stem cell transplantation activity? An EBMT analysis. Bone Marrow Transplant 2008; 42 (Suppl 1): S7–S10.

    Article  Google Scholar 

  2. Gratwohl A, Baldomero H, Schwendener A, Rocha V, Frauendorfer K et al. The EBMT activity survey 2007 with focus on allogeneic HSCT for AML and novel cellular therapies. Bone Marrow Transplant 2009; 43: 275–291.

    Article  CAS  Google Scholar 

  3. Bensinger WI, Longin K, Appelbaum F, Rowley S, Weaver C, Lilleby K et al. Peripheral blood stem cells (PBSCs) collected after recombinant granulocyte colony stimulating factor (rhG-CSF): an analysis of factors correlating with the tempo of engraftment after transplantation. Br J Haematol 1994; 87: 825–831.

    Article  CAS  Google Scholar 

  4. Hartmann O, Le Corroller AG, Blaise D, Michon J, Philip I, Norol F et al. Peripheral blood stem cell and bone marrow transplantation for solid tumors and lymphomas: hematologic recovery and costs. A randomized, controlled trial. Ann Intern Med 1997; 126: 600–607.

    Article  CAS  Google Scholar 

  5. Weaver CH, Hazelton B, Birch R, Palmer P, Allen C, Schwartzberg L et al. An analysis of engraftment kinetics as a function of the CD34 content of peripheral blood progenitor cell collections in 692 patients after the administration of myeloablative chemotherapy. Blood 1995; 86: 3961–3969.

    CAS  Google Scholar 

  6. Benboubker L, Watier H, Carion A, Georget MT, Desbois I, Colombat P et al. Association between the SDF1-3′A allele and high levels of CD34(+) progenitor cells mobilized into peripheral blood in humans. Br J Haematol 2001; 113: 247–250.

    Article  CAS  Google Scholar 

  7. Bogunia-Kubik K, Gieryng A, Dlubek D, Lange A . The CXCL12-3′A allele is associated with a higher mobilization yield of CD34 progenitors to the peripheral blood of healthy donors for allogeneic transplantation. Bone Marrow Transplant 2009; 44: 273–278.

    Article  CAS  Google Scholar 

  8. Vasu S, Leitman SF, Tisdale JF, Hsieh MM, Childs RW, Barrett AJ et al. Donor demographic and laboratory predictors of allogeneic peripheral blood stem cell mobilization in an ethnically diverse population. Blood 2008; 112: 2092–2100.

    Article  CAS  Google Scholar 

  9. Calandra G, McCarty J, McGuirk J, Tricot G, Crocker SA, Badel K et al. AMD3100 plus G-CSF can successfully mobilize CD34+ cells from non-Hodgkin's lymphoma, Hodgkin's disease and multiple myeloma patients previously failing mobilization with chemotherapy and/or cytokine treatment: compassionate use data. Bone Marrow Transplant 2008; 41: 331–338.

    Article  CAS  Google Scholar 

  10. Fowler CJ, Dunn A, Hayes-Lattin B, Hansen K, Hansen L, Lanier K et al. Rescue from failed growth factor and/or chemotherapy HSC mobilization with G-CSF and plerixafor (AMD3100): an institutional experience. Bone Marrow Transplant 2009; 43: 909–917.

    Article  CAS  Google Scholar 

  11. Pusic I, Jiang SY, Landua S, Uy GL, Rettig MP, Cashen AF et al. Impact of mobilization and remobilization strategies on achieving sufficient stem cell yields for autologous transplantation. Biol Blood Marrow Transplant 2008; 14: 1045–1056.

    Article  CAS  Google Scholar 

  12. 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  Google Scholar 

  13. Galli SJ, Zsebo KM, Geissler EN . The kit ligand, stem cell factor. Adv Immunol 1994; 55: 1–96.

    CAS  PubMed  Google Scholar 

  14. Costa JJ, Demetri GD, Harrist TJ, Dvorak AM, Hayes DF, Merica EA et al. Recombinant human stem cell factor (kit ligand) promotes human mast cell and melanocyte hyperplasia and functional activation in vivo. J Exp Med 1996; 183: 2681–2686.

    Article  CAS  Google Scholar 

  15. Stiff P, Gingrich R, Luger S, Wyres MR, Brown RA, LeMaistre CF et al. A randomized phase 2 study of PBPC mobilization by stem cell factor and filgrastim in heavily pretreated patients with Hodgkin's disease or non-Hodgkin's lymphoma. Bone Marrow Transplant 2000; 26: 471–481.

    Article  CAS  Google Scholar 

  16. Chin-Yee IH, Keeney M, Stewart AK, Belch A, Bence-Buckler I, Couban S et al. Optimising parameters for peripheral blood leukapheresis after r-metHuG-CSF (filgrastim) and r-metHuSCF (ancestim) in patients with multiple myeloma: a temporal analysis of CD34(+) absolute counts and subsets. Bone Marrow Transplant 2002; 30: 851–860.

    Article  CAS  Google Scholar 

  17. To LB, Bashford J, Durrant S, MacMillan J, Schwarer AP, Prince HM et al. Successful mobilization of peripheral blood stem cells after addition of ancestim (stem cell factor) in patients who had failed a prior mobilization with filgrastim (granulocyte colony-stimulating factor) alone or with chemotherapy plus filgrastim. Bone Marrow Transplant 2003; 31: 371–378.

    Article  CAS  Google Scholar 

  18. Dawson MA, Schwarer AP, Muirhead JL, Bailey MJ, Bollard GM, Spencer A . Successful mobilization of peripheral blood stem cells using recombinant human stem cell factor in heavily pretreated patients who have failed a previous attempt with a granulocyte colony-stimulating factor-based regimen. Bone Marrow Transplant 2005; 36: 389–396.

    Article  CAS  Google Scholar 

  19. Herbert KE, Morgan S, Prince HM, Westerman DA, Wolf MM, Carney DA et al. Stem cell factor and high-dose twice daily filgrastim is an effective strategy for peripheral blood stem cell mobilization in patients with indolent lymphoproliferative disorders previously treated with fludarabine: results of a Phase II study with an historical comparator. Leukemia 2008; 23: 305–312.

    Article  Google Scholar 

  20. da Silva MG, Pimentel P, Carvalhais A, Barbosa I, Machado A, Campilho F et al. Ancestim (recombinant human stem cell factor, SCF) in association with filgrastim does not enhance chemotherapy and/or growth factor-induced peripheral blood progenitor cell (PBPC) mobilization in patients with a prior insufficient PBPC collection. Bone Marrow Transplant 2004; 34: 683–691.

    Article  CAS  Google Scholar 

  21. Panterne B, Sabatini C, Huyghe G, Maquin C, Mouillot L, TIissier MH . External quality controls of cellular products: the French experience. Cytotherapy 2006; 8(Suppl 1): 176.

  22. Pusic I, DiPersio JF . The use of growth factors in hematopoietic stem cell transplantation. Curr Pharm Des 2008; 14: 1950–1961.

    Article  CAS  Google Scholar 

  23. MacVittie TJ, Farese AM, Davis TA, Lind LB, McKearn JP . Myelopoietin, a chimeric agonist of human interleukin 3 and granulocyte colony-stimulating factor receptors, mobilizes CD34+ cells that rapidly engraft lethally x-irradiated nonhuman primates. Exp Hematol 1999; 27: 1557–1568.

    Article  CAS  Google Scholar 

  24. del Giglio A, Eniu A, Ganea-Motan D, Topuzov E, Lubenau H . XM02 is superior to placebo and equivalent to Neupogen in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy. BMC Cancer 2008; 8: 332.

    Article  CAS  Google Scholar 

  25. Varki R, Pequignot E, Leavitt MC, Ferber A, Kraft WK . A glycosylated recombinant human granulocyte colony stimulating factor produced in a novel protein production system (AVI-014) in healthy subjects: a first-in human, single dose, controlled study. BMC Clin Pharmacol 2009; 9: 2.

    Article  Google Scholar 

  26. Viens P, Chabannon C, Pouillard P, Janvier M, Brugger W, Blay JY et al. Randomized, controlled, dose-range study of Ro 25-8315 given before and after a high-dose combination chemotherapy regimen in patients with metastatic or recurrent breast cancer patients. J Clin Oncol 2002; 20: 24–36.

    Article  CAS  Google Scholar 

  27. Bruns I, Steidl U, Kronenwett R, Fenk R, Graef T, Rohr UP et al. A single dose of 6 or 12 mg 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  Google Scholar 

  28. Ballen KK, Shpall EJ, Avigan D, Yeap BY, Fisher DC, McDermott K et al. Phase I trial of parathyroid hormone to facilitate stem cell mobilization. Biol Blood Marrow Transplant 2007; 13: 838–843.

    Article  CAS  Google Scholar 

  29. Carlo-Stella C, Di Nicola M, Milani R, Guidetti A, Magni M, Milanesi M et al. Use of recombinant human growth hormone (rhGH) plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) for the mobilization and collection of CD34+ cells in poor mobilizers. Blood 2004; 103: 3287–3295.

    Article  CAS  Google Scholar 

  30. Liles WC, Broxmeyer HE, Rodger E, Wood B, Hubel K, Cooper S et al. Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist. Blood 2003; 102: 2728–2730.

    Article  CAS  Google Scholar 

  31. Devine SM, Vij R, Rettig M, Todt L, McGlauchlen K, Fisher N et al. Rapid mobilization of functional donor hematopoietic cells without G-CSF using AMD3100, an antagonist of the CXCR4/SDF-1 interaction. Blood 2008; 112: 990–998.

    Article  CAS  Google Scholar 

  32. 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  Google Scholar 

  33. Devine SM, Flomenberg N, Vesole DH, Liesveld J, Weisdorf D, Badel K et al. Rapid mobilization of CD34+ cells following administration of the CXCR4 antagonist AMD3100 to patients with multiple myeloma and non-Hodgkin's lymphoma. J Clin Oncol 2004; 22: 1095–1102.

    Article  CAS  Google Scholar 

  34. 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 

  35. Stiff P, Micallef I, McCarthy P, Magalhaes-Silverman M, Weisdorf D, Territo M et al. Treatment with plerixafor in non-Hodgkin's lymphoma and multiple myeloma patients to increase the number of peripheral blood stem cells when given a mobilizing regimen of G-CSF: implications for the heavily pretreated patient. Biol Blood Marrow Transplant 2009; 15: 249–256.

    Article  CAS  Google Scholar 

  36. Giralt S, Stadtmauer EA, Harousseau JL, Palumbo A, Bensinger W, Comenzo RL et al. International myeloma working group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100). Leukemia 2009; 23: 1904–1912.

    Article  CAS  Google Scholar 

  37. Kumar S, Giralt S, Stadtmauer EA, Harousseau JL, Palumbo A, Bensinger W et al. Mobilization in myeloma revisited: IMWG consensus perspectives on stem cell collection following initial therapy with thalidomide-, lenalidomide-, or bortezomib-containing regimens. Blood 2009; 114: 1729–1735.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors deeply acknowledge the strong support of all the staff at Amgen France for providing ancestim to patients who benefited from an ATU, and Agnes Balog and her team at Parexel France for organizing the distribution of ancestim to hospitals and the collection of data from treated patients. The following centres requested ATU for ancestim for one or several patients: Hôpitaux Henri-Mondor, Avicenne, Beaujon, Saint-Antoine, Saint-Louis, Necker, Paul Brousse, Tenon, Hôpital Européen Georges Pompidou all at Assistance Publique des Hôpitaux de Paris (AP-HP); Centres Hospitaliers et Universitaires de Bordeaux, Nancy, Brest, Caen, Reims, Toulouse, Lille, Besançon, Poitiers, Clermont-Ferrand, Nice, Rennes, Tours, Lyon, Limoges, Strasbourg; Centres de Lutte Contre le Cancer Caen (Centre François Baclesse), Rouen (Centre Henri Becquerel), Paris (Institut Curie), Clermont-Ferrand (Centre Jean Perrin), Montpellier (Centre Val d’Aurelle), Bordeaux (Institut Bergonié), Nancy (Centre Alexis Vautrin), Toulouse (Institut Claudius Regaud); Centres Hospitaliers de Metz, Mulhouse, Meaux, Argenteuil, Saint-Denis de la Réunion, Corbeil-Essonnes, Avignon, Blois, Pontoise, Boulogne-sur-Mer, Valenciennes, Lens; Army Hospitals in Percy and Toulon, Hôpital Foch, Clinique Victor Hugo in Le Mans, Polyclinique du Parc in Caen and Polyclinique Nord-Aquitaine in Bordeaux. The authors thank all personnel at the departments of Hematology and Medical Oncology within these institutions, and at associated apheresis departments, for their help in collecting data presented in this report.

Author information

Authors and Affiliations

  1. Institut Gustave Roussy, Villejuif, France

    V Lapierre & A Auperin

  2. Centre Hospitalier et Universitaire, Montpellier, France

    J-F Rossi

  3. Inserm, CIC-B509, Centre d’Investigations Cliniques en Biothérapie, Montpellier, France

    J-F Rossi

  4. Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Paris, France

    F Heshmati

  5. Hôpital de la Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris, Paris, France

    N Azar

  6. Hôpital de l’Hôtel-Dieu, Assistance Publique des Hôpitaux de Paris, Paris, France

    A Vekhof

  7. Centre Hospitalier et Universitaire, Grenoble, France

    C Makowski

  8. Centre Hospitalier et Universitaire, Nantes, France

    P Moreau

  9. Centre Hospitalier et Universitaire, Dijon, France

    D Caillot

  10. Institut Paoli-Calmettes, Marseille, France

    C Chabannon

  11. Inserm, CIC-B510, Centre d’Investigations Cliniques en Biothérapie, Marseille, France

    C Chabannon

Authors
  1. V Lapierre
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J-F Rossi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F Heshmati
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N Azar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Vekhof
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C Makowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P Moreau
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. D Caillot
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A Auperin
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. C Chabannon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V Lapierre.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

This work was reported in part at the 2004 American Society for Clinical Oncology (ASCO) annual meeting and the 2007 American Society of Hematology (ASH) annual meeting.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lapierre, V., Rossi, JF., Heshmati, F. et al. Ancestim (r-metHuSCF) plus filgrastim and/or chemotherapy for mobilization of blood progenitors in 513 poorly mobilizing cancer patients: the French compassionate experience. Bone Marrow Transplant 46, 936–942 (2011). https://doi.org/10.1038/bmt.2010.231

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2010.231

Keywords

This article is cited by

Search

Advanced search

Quick links