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:

Progenitor Cell Mobilisation

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

Abstract

This randomized, controlled study compared the ability to mobilize and collect an optimal target yield of 5 × 106 CD34+ cells/kg using stem cell factor (SCF; 20 μg/ kg/day) plus filgrastim (G-CSF; 10 μg/kg/day) vsfilgrastim alone (10 μg/kg/day) in 102 patients diagnosed with non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD), who were prospectively defined as being heavily pretreated. Leukapheresis began on day 5 of cytokine administration and continued daily until the target yield was reached, or until a maximum of five leukaphereses had been performed. Compared with the filgrastim-alone group (n = 54), the SCF plus filgrastim group (n = 48) showed an increase in the proportion of patients reaching the target yield within five leukaphereses (44% vs 17%, P = 0.002); reduction in the number of leukaphereses required to reach the target yield (P = 0.003); reduction in the proportion of patients failing to reach a minimum yield of 1 x 106 CD34+ cells/kg to proceed to transplant (16% vs26%, P = NS); increase in the median yield of CD34+ cells per leukapheresis (0.73 × 106/kg vs0.48 × 106/kg, P = 0.04); and an increase in the median total CD34+ cells collected within five leukaphereses (3.6 × 106/kg vs 2.4 × 106/kg, P = 0.05). All patients receiving SCF were premedicated (antihistamines and albuterol), and treatment was generally well tolerated. Five patients experienced severe mast cell-mediated reactions, none of which were life-threatening. In this study of heavily pretreated lymphoma patients, SCF plus filgrastim was more effective than filgrastim alone for mobilizing PBPC for harvesting and transplantation after high-dose chemotherapy. Bone Marrow Transplantation (2000) 26, 471–481.

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

Access options

Buy this article

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Sheridan WP, Begley CG, Juttner CA et al. Effect of peripheral-blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy Lancet 1992 339: 640–644

    Article  CAS  PubMed  Google Scholar 

  2. Schmitz N, Linch DC, Dreger P et al. Randomized trial of filgrastim-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients Lancet 1996 347: 353–357

    Article  CAS  PubMed  Google Scholar 

  3. Bensinger W, Appelbaum F, Rowley S et al. Factors that influence collection and engraftment of autologous peripheral-blood stem cells J Clin Oncol 1995 13: 2547–2555

    Article  CAS  PubMed  Google Scholar 

  4. Bensinger WI, Longin K, Applebaum F 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  PubMed  Google Scholar 

  5. Pettengell R, Morgenstern GR, Woll PJ et al. Peripheral blood progenitor cell transplantation in lymphoma and leukemia using a single apheresis Blood 1993 82: 3770–3777

    CAS  PubMed  Google Scholar 

  6. Knudsen LM, Gaarsdal E, Jensen L et al. Improved priming for mobilization of and optimal timing for harvest of peripheral blood stem cells J Hematother 1996 5: 399–406

    Article  CAS  PubMed  Google Scholar 

  7. Sutherland DR, Anderson L, Keeney M et al. The ISHAGE guidelines for CD34+ cell determination by flow cytometry. International Society of Hematotherapy and Graft Engineering J Hematother 1996 5: 213–226

    Article  CAS  PubMed  Google Scholar 

  8. Demirer T, Buckner CD, Bensinger WI . Optimization of peripheral blood stem cell mobilization Stem Cells 1996 14: 106–116

    Article  CAS  PubMed  Google Scholar 

  9. Tricot G, Jagannath S, Vesole DH et al. Peripheral blood stem cell transplants for multiple myeloma: identification of favorable variables for rapid engraftment in 225 patients Blood 1995 85: 588–596

    CAS  PubMed  Google Scholar 

  10. Weaver CH, Hazelton B, Birch R 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  PubMed  Google Scholar 

  11. Kiss JE, Rybka WB, Winkelstein A et al. Relationship of CD34+ cell dose to early and late hematopoiesis following autologous peripheral blood stem cell transplantation Bone Marrow Transplant 1997 19: 303–310

    Article  CAS  PubMed  Google Scholar 

  12. Dercksen MW, Rodenhuis S, Dirkson MKA et al. Subsets of CD34+ cells and rapid hematopoietic recovery after peripheral blood stem cell transplantation J Clin Oncol 1995 13: 1922–1932

    Article  CAS  PubMed  Google Scholar 

  13. Siena S, Bregni M, Brando B et al. Flow cytometry for clinical estimation of circulating hematopoietic progenitors for autologous transplantation in cancer patients Blood 1991 77: 400–409

    CAS  PubMed  Google Scholar 

  14. Brecher ME, Sims L, Schmitz J et al. North American multicenter study on flow cytometric enumeration of CD34+ hematopoietic stem cells J Hematother 1996 5: 227–236

    Article  CAS  PubMed  Google Scholar 

  15. Glaspy JA, Shpall EJ, LeMaistre CF et al. Peripheral blood progenitor cell mobilization utilizing stem cell factor in combination with filgrastim in breast cancer patients Blood 1997 90: 2939–2951

    CAS  PubMed  Google Scholar 

  16. Lieschke GJ, Foote M, Morstyn G . Hematopoietic growth factors in cancer chemotherapy. In: Pinedo HM, Longo DL, Chabner BA (eds) Cancer Chemotherapy and Biological Response Modifiers, Annual 17 Elsevier Science: New York 1997 pp363–389

    Google Scholar 

  17. Moskowitz CH, Stiff P, Gordon MS et al. Recombinant methionyl human stem cell factor and filgrastim for peripheral blood progenitor cell mobilization and transplantation in non-Hodgkin's lymphoma patients-results of a phase I/II trial Blood 1997 89: 3136–3147

    CAS  PubMed  Google Scholar 

  18. Weaver A, Chang J, Wrigley E et al. Randomized comparison of progenitor-cell mobilization using chemotherapy, stem-cell factor, and filgrastim or chemotherapy plus filgrastim alone in patients with ovarian cancer J Clin Oncol 1998 16: 2601–2612

    Article  CAS  PubMed  Google Scholar 

  19. Begley CG, Basser R, Mansfield R et al. Enhanced levels and enhanced clonogenic capacity of blood progenitor cells following administration of stem cell factor plus granulocyte colony-stimulating factor to humans Blood 1997 90: 3378–3389

    CAS  PubMed  Google Scholar 

  20. Basser RL, To LB, Begley CG et al. Rapid hematopoietic recovery after multicycle high-dose chemotherapy: enhancement of filgrastim-induced progenitor-cell mobilization by recombinant human stem-cell factor J Clin Oncol 1998 16: 1899–1908

    Article  CAS  PubMed  Google Scholar 

  21. Shpall EJ, Wheeler CA, Turner SA et al. A randomized phase 3 study of peripheral blood progenitor cell mobilization by stem cell factor and filgrastim in high-risk breast cancer patients Blood 1991 93: 2491–2501

    Google Scholar 

  22. Rasko JEJ, Basser RL, Boyd J et al. Multilineage mobilization of peripheral blood progenitor cells in humans following administration of PEG-rHuMGDF Br J Haematol 1997 97: 871–880

    Article  CAS  PubMed  Google Scholar 

  23. Basser RL, Rasko JEJ, Clarke K et al. Randomized, blinded, placebo-controlled phase I trial of pegylated recombinant human megakaryocyte growth and development factor with filgrastim after dose-intensive chemotherapy in patients with advanced cancer Blood 1997 89: 3118–3128

    CAS  PubMed  Google Scholar 

  24. Lebsack ME, McKenna HJ, Hoek JA et al. Safety of FLT3 ligand in healthy volunteers Blood 1997 90: 170 (Abstr.751)

    Google Scholar 

  25. DiPersio JF, Abboud CN, Schuster MW et al. Phase II study of mobilization of PBSC by administration of daniplestim (SC-55494) and G-CSF in patients with breast cancer or lymphoma Proc Am Soc Clin Oncol 1997 16: 87 (Abstr.306)

    Google Scholar 

  26. Morstyn G, Brown S, Gordon M et al. Stem cell factor is a potent synergistic factor in hematopoiesis Oncology 1994 51: 205–214

    Article  CAS  PubMed  Google Scholar 

  27. Glaspy J . Clinical applications of stem cell factor Curr Opin Hematol 1996 3: 223–229

    Article  CAS  PubMed  Google Scholar 

  28. Broudy V . Stem cell factor and hematopoiesis Blood 1997 90: 1345–1364

    CAS  PubMed  Google Scholar 

  29. Briddell RA, Hartley CA, Smith KA, McNiece IK . Recombinant rat stem cell factor synergizes with recombinant human granulocyte colony-stimulating factor in vivo in mice to mobilize peripheral blood progenitor cells that have enhancedrepopulating potential Blood 1993 82: 1720–1723

    CAS  PubMed  Google Scholar 

  30. McNiece IK, Briddell RA, Hartley CA et al. Stem cell factor enhances in vivo effects of granulocyte colony stimulating factor for stimulating mobilization of peripheral blood progenitor cells that have enhanced repopulating potential Stem Cells 1993 11: (Suppl.2) 36–41

    Article  CAS  PubMed  Google Scholar 

  31. Yan XQ, Briddell R, Hartley C et al. Mobilization of long-term reconstituting cells in mice by the combination of stem cell factor plus granulocyte colony-stimulating factor Blood 1994 84: 795–799

    CAS  PubMed  Google Scholar 

  32. de Revel T, Applebaum FR, Storb et al. Effects of granulocyte colony-stimulating factor and stem cell factor, alone and in combination, on the mobilization of peripheral blood cells that engraft lethally irradiated dogs Blood 1994 83: 3795–3799

    CAS  PubMed  Google Scholar 

  33. Andrews RG, Briddell RA, Knitter GH et al. In vivo synergy between recombinant human stem cell factor and recombinant human granulocyte colony-stimulating factor in baboons; enhanced circulation of progenitor cells Blood 1994 84: 800–810

    CAS  PubMed  Google Scholar 

  34. Andrews RG, Briddell RA, Knitter GH et al. Rapid engraftment by peripheral blood progenitor cells mobilized by recombinant human stem cell factor and recombinant human granulocyte colony-stimulating factor in nonhuman primates Blood 1995 85: 15–20

    CAS  PubMed  Google Scholar 

  35. Moskowitz CH, Glassman JR, Wuest D et al. Factors affecting mobilization of peripheral blood progenitor cells in patients with lymphoma Clin Cancer Res 1998 4: 311–316

    CAS  PubMed  Google Scholar 

  36. Stiff PJ, Dahlberg S, Forman SJ et al. Autologous bone marrow transplantation for patients with relapsed or refractory diffuse aggressive non-Hodgkin's lymphoma: value of augmented preparative regimens: a Southwest Oncology Group trial J Clin Oncol 1998 16: 48–55

    Article  CAS  PubMed  Google Scholar 

  37. Weaver CH, Bensinger WI, Appelbaum F et al. Phase I study of high-dose busulfan, melphalan, thiotepa with autologous stem cell support in patients with refractory malignancies Bone Marrow Transplant 1994 14: 813–819

    CAS  PubMed  Google Scholar 

  38. Jaganath S, Dicke KA, Armitage JO et al. High-dose cyclophosphamide, carmustine and etoposide and autologous bone marrow transplantation for relapsed Hodgkin's Disease Ann Intern Med 1986 104: 163–168

    Article  Google Scholar 

  39. Collett D . Modeling Survival Data in Medical Research Chapman and Hall: London 1994

    Book  Google Scholar 

  40. Costa JJ, Demetri GD, Harrist TJ 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  PubMed  Google Scholar 

  41. Crawford J, Ozer H, Stoller R et al. Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer New Engl J Med 1991 325: 164–170

    Article  CAS  PubMed  Google Scholar 

  42. Philip T, Guglielmi C, Hagenbeek A . Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma New Engl J Med 1995 333: 1540–1545

    Article  CAS  PubMed  Google Scholar 

  43. Pettengell R . Survival benefit from high-dose therapy with autologous blood progenitor-cell transplantation in poor-prognosis non-Hodgkin's lymphoma J Clin Oncol 1996 14: 586–592

    Article  CAS  PubMed  Google Scholar 

  44. Haioun C, Lepage E, Gisselbrecht C et al. Benefit of autologous bone marrow transplantation over sequential chemotherapy in poor-risk aggressive non-Hodgkin's lymphoma: updated results of the prospective study LNH87-2 J Clin Oncol 1997 5: 1131–1137

    Article  Google Scholar 

  45. Gianni AM, Bregni M, Siena S et al. High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma New Engl J Med 1997 336: 1290–1297

    Article  CAS  PubMed  Google Scholar 

  46. Laport GF, Zimmerman TM, Grinblatt DL et al. CD34+ peripheral blood stem cell (PBSC) dose influences engraftment kinetics and other relevant clinical variables Proc Am Soc Clin Oncol 1996 15: 333 (Abstr. 956)

    Google Scholar 

  47. Schiller G, Vescio R, Freytes C et al. Transplantation of CD34+ peripheral blood progenitor cells after high dose chemotherapy for patients with advanced multiple myeloma Blood 1995 86: 390–397

    CAS  PubMed  Google Scholar 

  48. Bender JG, To LB, Williams S, Schwartzberg, LS . Defining a therapeutic dose of peripheral blood stem cells J Hematother 1992 1: 329–241

    Article  CAS  PubMed  Google Scholar 

  49. Borson R, Brown R, Hendricks D et al. Hematopoietic recovery after stem cell transplantation: impact of CD34+ cell dose and method of mobilization Blood 1994 84: 349 (Abstr. 1381)

    Google Scholar 

  50. Haas R, Mohle R, Fruhauf S et al. Patient characteristics associated with successful mobilizing and autografting of peripheral blood progenitor cells in malignant lymphoma Blood 1994 83: 3787–3794

    CAS  PubMed  Google Scholar 

  51. Haynes A, Hunter A, McQuaker G et al. Engraftment characteristics of peripheral blood stem cells mobilised withcyclophosphamide and the delayed addition of G-CSF Bone Marrow Transplant 1995 16: 359–363

    CAS  PubMed  Google Scholar 

  52. Schwella N, Beyer J, Schwaner I et al. Impact of preleukapheresis cell counts on collection results and correlation ofprogenitor-cell dose with engraftment after high-dose chemotherapy in patients with germ cell cancer J Clin Oncol 1996 14: 1114–1121

    Article  CAS  PubMed  Google Scholar 

  53. Glaspy JA, Lu ZJ, Wheeler C et al. Economic rationale for infusing optimal numbers of CD34+ cells in peripheral blood progenitor transplants (PBPCT) Blood 1997 90: 370 (Abstr.1646)

    Google Scholar 

  54. Weaver CH, Birch R, Schulman KA . Effect of cell dose on resource utilization in patients undergoing transplant with peripheral blood progenitor cells Blood 1997 90: 370 (Abstr.1647)

    Google Scholar 

  55. Chabannon C, Le Coroller AG, Faucher C et al. Patient condition affects the collection of peripheral blood progenitors after priming with recombinant granulocyte colony-stimulating factor J Hematother 1995 4: 171–179

    Article  CAS  PubMed  Google Scholar 

  56. Morton J, Morton A, Bird R et al. Predictors for optimal mobilization and subsequent engraftment of peripheral blood progenitor cells following intermediate dose cyclophosphamide and G-CSF Leuk Res 1997 21: 21–27

    Article  CAS  PubMed  Google Scholar 

  57. Neben S, Hemman S, Montgomery M et al. Hematopoietic stem cell deficit of transplanted bone marrow previously exposed to cytotoxic agents Exp Hematol 1993 21: 156–162

    CAS  PubMed  Google Scholar 

  58. Glaspy JA, Snyder C, Lu J et al. A resource-based cost analysis of G-CSF-primed peripheral blood progenitor cell procurement (PBPCP) Proc Am Soc Clin Oncol 1997 16: 412 (Abstr.1471)

    Google Scholar 

  59. Goldberg SL, Mangan KF, Klumpp TR et al. Complications of peripheral blood stem cell harvesting: review of 554 PBSC leukaphereses J Hematother 1995 4: 85–90

    Article  CAS  PubMed  Google Scholar 

  60. Tricot G, Jagannath S, Desikan KR et al. Superior mobilization of peripheral blood progenitor cells (PBPC) withr-metHuSCF (SCF) and r-metHuG-CSF (filgrastim) in heavily pretreated multiple myeloma (MM) patients Blood 1996 88: 388a (Abstr.1540)

    Google Scholar 

  61. Harousseau JL, Facon T, Maloisel F et al. Stem cell factor in combination with filgrastim following chemotherapy improves peripheral blood progenitor cell mobilisation Br J Haematol 1998 102: 152 (Abstr.0–0600)

    Google Scholar 

Download references

Acknowledgements

Administrative costs for the conduct of this study were supported in part by Amgen Inc. The authors would like to thank Carol Cutrone, Beth Kaufman, Cheryl Sickles, Elisa Beck, Carol Rush, Kathy Derr, Sheryl Oliverson, Maureen Hougham, Doshia James, Robin Inabinet, Vicki O'Brien, Julie Morelli, Kristi Snead, Lisa Glenn, Terry Brehm, Kathleen Shannon-Dorcy, Lisa Gaynes, Joya Milano, Jane Quigley, Anne Sharpe, Sara Rasti, Mark Davis, Robyn Murphy-Filkins, Kathy Jelaca-Maxwell, Jerome Hill, Doug Okamoto, Neal Birkett, Hillary O'Kelly, Jody Tyrrell, Erik Olson, Wade Lovelace, and Carol Brannan for their contributions towards this research; and Keith Langley for assistance in preparation of the manuscript.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stiff, P., Gingrich, R., Luger, S. 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 26, 471–481 (2000). https://doi.org/10.1038/sj.bmt.1702531

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1702531

Keywords

This article is cited by

Search

Quick links