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.

  • Review
  • Published:

Pegfilgrastim for PBSC mobilization and autologous haematopoietic SCT

Abstract

To date, G-CSF is the most favoured cytokine administered for PBSC mobilization because of its great efficacy and lack of serious toxicity. Recently, a pegylated filgrastim (pegfilgrastim) has been introduced. Attachment of the polyethylene glycol (PEG) moiety reduces renal excretion and masks proteolytic cleavage sites resulting in elevated G-CSF serum levels for up to 14 days after a single injection. As single-dose pegfilgrastim had similar effects in the prophylaxis of chemotherapy-induced neutropenia as the daily administration of the unconjugated drug, its capability for the mobilization of haematopoietic stem and progenitor cells has been assessed and presented to be at least equal to that of conventional G-CSF. Administration of pegfilgrastim following high-dose therapy and autologous blood SCT (BSCT) shortened the time to myeloid recovery as seen in conventional G-CSF. Plasma G-CSF levels were about 1 log higher with pegfilgrastim, but in the setting of autologous BSCT this did not translate into a faster haematopoietic recovery. Only few data exist on the biological effects of pegfilgrastim. Still, these data suggest that pegfilgrastim–stimulation results in different functional properties of haematopoietic stem and progenitor cells compared with G-CSF.

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

Similar content being viewed by others

References

  1. Appelbaum FR, Herzig GP, Ziegler JL, Graw RG, Levine AS, Deisseroth AB . Successful engraftment of cryopreserved autologous bone marrow in patients with malignant lymphoma. Blood 1978; 52: 85–95.

    CAS  PubMed  Google Scholar 

  2. Abrams RA, Deisseroth AB . Prospects for accelerating hematopoietic recovery following myelosuppressive therapy by using autologous, cryopreserved hematopoietic stem cells collected solely from the peripheral blood. Exp Hematol 1979; 7 (Suppl 5): 107–115.

    PubMed  Google Scholar 

  3. Haas R, Ho AD, Bredthauer U, Cayeux S, Egerer G, Knauf W et al. Successful autologous transplantation of blood stem cells mobilized with recombinant human granulocyte-macrophage colony-stimulating factor. Exp Hematol 1990; 18: 94–98.

    CAS  PubMed  Google Scholar 

  4. Neben S, Marcus K, Mauch P . Mobilization of hematopoietic stem and progenitor cell subpopulations from the marrow to the blood of mice following cyclophosphamide and/or granulocyte colony-stimulating factor. Blood 1993; 81: 1960–1967.

    CAS  PubMed  Google Scholar 

  5. Siena S, Bregni M, Brando B, Ravagnani F, Bonadonna G, Gianni AM . Circulation of CD34+ hematopoietic stem cells in the peripheral blood of high-dose cyclophosphamide-treated patients: enhancement by intravenous recombinant human granulocyte-macrophage colony-stimulating factor. Blood 1989; 74: 1905–1914.

    CAS  PubMed  Google Scholar 

  6. Haas R, Witt B, Mohle R, Goldschmidt H, Hohaus S, Fruehauf S et al. Sustained long-term hematopoiesis after myeloablative therapy with peripheral blood progenitor cell support. Blood 1995; 85: 3754–3761.

    CAS  PubMed  Google Scholar 

  7. Schmitz N, Linch DC, Dreger P, Goldstone AH, Boogaerts MA, Ferrant A et al. Randomised 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 

  8. Tabbara IA, Ghazal CD, Ghazal HH . The clinical applications of granulocyte colony-stimulating factor in hematopoietic stem cell transplantation: a review. Anticancer Res 1996; 16: 3901–3905.

    CAS  PubMed  Google Scholar 

  9. Roskos LK, Lum P, Lockbaum P, Schwab G, Yang BB . Pharmacokinetic/pharmacodynamic modeling of pegfilgrastim in healthy subjects. J Clin Pharmacol 2006; 46: 747–757.

    Article  CAS  PubMed  Google Scholar 

  10. Martin-Murea S, Voso MT, Hohaus S, Pforsich M, Fruehauf S, Goldschmidt H et al. The dose of granulocyte colony-stimulating factor administered following cytotoxic chemotherapy is not related to the rebound level of circulating CD34+ haemopoietic progenitor cells during marrow recovery. Br J Haematol 1998; 101: 582–585.

    Article  CAS  PubMed  Google Scholar 

  11. Kobbe G, Sohngen D, Bauser U, Schneider P, Germing U, Thiele KP et al. Factors influencing G-CSF-mediated mobilization of hematopoietic progenitor cells during steady-state hematopoiesis in patients with malignant lymphoma and multiple myeloma. Ann Hematol 1999; 78: 456–462.

    Article  CAS  PubMed  Google Scholar 

  12. Haas R, Mohle R, Fruhauf S, Goldschmidt H, Witt B, Flentje M 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 

  13. Goldschmidt H, Hegenbart U, Wallmeier M, Hohaus S, Haas R . Factors influencing collection of peripheral blood progenitor cells following high-dose cyclophosphamide and granulocyte colony-stimulating factor in patients with multiple myeloma. Br J Haematol 1997; 98: 736–744.

    Article  CAS  PubMed  Google Scholar 

  14. Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 2003; 349: 2495–2502.

    Article  CAS  PubMed  Google Scholar 

  15. Vose JM, Crump M, Lazarus H, Emmanouilides C, Schenkein D, Moore J et al. Randomized, multicenter, open-label study of pegfilgrastim compared with daily filgrastim after chemotherapy for lymphoma. J Clin Oncol 2003; 21: 514–519.

    Article  CAS  PubMed  Google Scholar 

  16. 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  PubMed  Google Scholar 

  17. Johnston E, Crawford J, Blackwell S, Bjurstrom T, Lockbaum P, Roskos L et al. randomized, dose-escalation study of SD/01 compared with daily filgrastim in patients receiving chemotherapy. J Clin Oncol 2000; 18: 2522–2528.

    Article  CAS  PubMed  Google Scholar 

  18. 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 

  19. 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  PubMed  Google Scholar 

  20. Russell N, Mesters R, Schubert J, Boogaerts M, Johnsen HE, Canizo CD et al. A phase 2 pilot study of pegfilgrastim and filgrastim for mobilizing peripheral blood progenitor cells in patients with non-Hodgkin's lymphoma receiving chemotherapy. Haematologica 2008; 93: 405–412.

    Article  CAS  PubMed  Google Scholar 

  21. Fenk R, Hieronimus N, Steidl U, Bruns I, Graef T, Zohren F et al. Sustained G-CSF plasma levels following administration of pegfilgrastim fasten neutrophil reconstitution after high-dose chemotherapy and autologous blood stem cell transplantation in patients with multiple myeloma. Exp Hematol 2006; 34: 1296–1302.

    Article  CAS  PubMed  Google Scholar 

  22. Haas R, Gericke G, Witt B, Cayeux S, Hunstein W . Increased serum levels of granulocyte colony-stimulating factor after autologous bone marrow or blood stem cell transplantation. Exp Hematol 1993; 21: 109–113.

    CAS  PubMed  Google Scholar 

  23. Tricot G, Barlogie B, Zangari M, van RF, Hoering A, Szymonifka J et al. Mobilization of peripheral blood stem cells in myeloma with either pegfilgrastim or filgrastim following chemotherapy. Haematologica 2008; 93: 1739–1742.

    Article  CAS  PubMed  Google Scholar 

  24. Isidori A, Tani M, Bonifazi F, Zinzani P, Curti A, Motta MR et al. Phase II study of a single pegfilgrastim injection as an adjunct to chemotherapy to mobilize stem cells into the peripheral blood of pretreated lymphoma patients. Haematologica 2005; 90: 225–231.

    CAS  PubMed  Google Scholar 

  25. Nosari A, Cairoli R, Ciapanna D, Gargantini L, Intropido L, Barate C et al. Efficacy of single dose pegfilgrastim in enhancing the mobilization of CD34+ peripheral blood stem cells in aggressive lymphoma patients treated with cisplatin-aracytin-containing regimens. Bone Marrow Transplant 2006; 38: 413–416.

    Article  CAS  PubMed  Google Scholar 

  26. 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 

  27. Fruehauf S, Klaus J, Huesing J, Veldwijk MR, Buss EC, Topaly J et al. Efficient mobilization of peripheral blood stem cells following CAD chemotherapy and a single dose of pegylated G-CSF in patients with multiple myeloma. Bone Marrow Transplant 2007; 39: 743–750.

    Article  CAS  PubMed  Google Scholar 

  28. Haas R, Ehrhardt R, Witt B, Goldschmidt H, Hohaus S, Pforsich M et al. Autografting with peripheral blood stem cells mobilized by sequential interleukin-3/granulocyte-macrophage colony-stimulating factor following high-dose chemotherapy in non-Hodgkin's lymphoma. Bone Marrow Transplant 1993; 12: 643–649.

    CAS  PubMed  Google Scholar 

  29. Stiff PJ . Management strategies for the hard-to-mobilize patient. Bone Marrow Transplant 1999; 23 (Suppl 2): S29–S33.

    Article  PubMed  Google Scholar 

  30. Cashen A, Lopez S, Gao F, Calandra G, MacFarland R, Badel K et al. A phase II study of plerixafor (AMD3100) plus G-CSF for autologous hematopoietic progenitor cell mobilization in patients with Hodgkin lymphoma. Biol Blood Marrow Transplant 2008; 14: 1253–1261.

    Article  CAS  PubMed  Google Scholar 

  31. Fricker SP . A novel CXCR4 antagonist for hematopoietic stem cell mobilization. Expert Opin Investig Drugs 2008; 17: 1749–1760.

    Article  CAS  PubMed  Google Scholar 

  32. Jacoub JF, Suryadevara U, Pereyra V, Colon D, Fontelonga A, Mackintosh FR et al. Mobilization strategies for the collection of peripheral blood progenitor cells: Results from a pilot study of delayed addition G-CSF following chemotherapy and review of the literature. Exp Hematol 2006; 34: 1443–1450.

    Article  CAS  PubMed  Google Scholar 

  33. Kroger N, Renges H, Kruger W, Gutensohn K, Loliger C, Carrero I et al. A randomized comparison of once versus twice daily recombinant human granulocyte colony-stimulating factor (filgrastim) for stem cell mobilization in healthy donors for allogeneic transplantation. Br J Haematol 2000; 111: 761–765.

    CAS  PubMed  Google Scholar 

  34. 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 

  35. 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 

  36. Hosing C, Qazilbash MH, Kebriaei P, Giralt S, Davis MS, Popat U et al. Fixed-dose single agent pegfilgrastim for peripheral blood progenitor cell mobilisation in patients with multiple myeloma. Br J Haematol 2006; 133: 533–537.

    Article  CAS  PubMed  Google Scholar 

  37. Bruns I, Steidl U, Fischer JC, Czibere A, Kobbe G, Raschke S et al. Pegylated granulocyte colony-stimulating factor mobilizes CD34+ cells with different stem and progenitor subsets and distinct functional properties in comparison with unconjugated granulocyte colony-stimulating factor. Haematologica 2008; 93: 347–355.

    Article  CAS  PubMed  Google Scholar 

  38. Sarkar CA, Lowenhaupt K, Wang PJ, Horan T, Lauffenburger DA . Parsing the effects of binding, signaling, and trafficking on the mitogenic potencies of granulocyte colony-stimulating factor analogues. Biotechnol Prog 2003; 19: 955–964.

    Article  CAS  PubMed  Google Scholar 

  39. Morris ES, MacDonald KP, Hill GR . Stem cell mobilization with G-CSF analogs: a rational approach to separate GVHD and GVL? Blood 2006; 107: 3430–3435.

    Article  CAS  PubMed  Google Scholar 

  40. van AM, Vellenga E, Fibbe WE, Kingma T, Uyl-de Groot CA . Cost analysis and quality of life assessment comparing patients undergoing autologous peripheral blood stem cell transplantation or autologous bone marrow transplantation for refractory or relapsed non-Hodgkin's lymphoma or Hodgkin's disease: a prospective randomised trial. Eur J Cancer 2001; 37: 1781–1789.

    Article  Google Scholar 

  41. McQuaker IG, Hunter AE, Pacey S, Haynes AP, Iqbal A, Russell NH . Low-dose filgrastim significantly enhances neutrophil recovery following autologous peripheral-blood stem-cell transplantation in patients with lymphoproliferative disorders: evidence for clinical and economic benefit. J Clin Oncol 1997; 15: 451–457.

    Article  CAS  PubMed  Google Scholar 

  42. Dekker A, Bulley S, Beyene J, Dupuis LL, Doyle JJ, Sung L . Meta-analysis of randomized controlled trials of prophylactic granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor after autologous and allogeneic stem cell transplantation. J Clin Oncol 2006; 24: 5207–5215.

    Article  CAS  PubMed  Google Scholar 

  43. Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L et al. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 2006; 24: 3187–3205.

    Article  CAS  PubMed  Google Scholar 

  44. Farese AM, MacVittie TJ, Roskos L, Stead RB . Hematopoietic recovery following autologous bone marrow transplantation in a nonhuman primate: effect of variation in treatment schedule with PEG-rHuMGDF. Stem Cells 2003; 21: 79–89.

    Article  CAS  PubMed  Google Scholar 

  45. Straka C, Oduncu F, Hinke A, Einsele H, Drexler E, Schnabel B et al. Responsiveness to G-CSF before leukopenia predicts defense to infection in high-dose chemotherapy recipients. Blood 2004; 104: 1989–1994.

    Article  CAS  PubMed  Google Scholar 

  46. Kuendgen A, Fenk R, Bruns I, Dommach M, Schutte A, Engers R et al. Splenic rupture following administration of pegfilgrastim in a patient with multiple myeloma undergoing autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 2006; 38: 69–70.

    Article  CAS  PubMed  Google Scholar 

  47. Nuamah NM, Goker H, Kilic YA, Dagmoura H, Cakmak A . Spontaneous splenic rupture in a healthy allogeneic donor of peripheral-blood stem cell following the administration of granulocyte colony-stimulating factor (g-csf). A case report and review of the literature. Haematologica 2006; 91: ECR08.

    PubMed  Google Scholar 

  48. Piccirillo N, De MS, De VS, Laurenti L, Chiusolo P, Sora F et al. Kinetics of peg-filgrastim after high-dose chemotherapy and autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 2007; 40: 579–583.

    Article  CAS  PubMed  Google Scholar 

  49. Staber PB, Holub R, Linkesch W, Schmidt H, Neumeister P . Fixed-dose single administration of Pegfilgrastim vs daily Filgrastim in patients with haematological malignancies undergoing autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 2005; 35: 889–893.

    Article  CAS  PubMed  Google Scholar 

  50. Jagasia MH, Greer JP, Morgan DS, Mineishi S, Kassim AA, Ruffner KL et al. Pegfilgrastim after high-dose chemotherapy and autologous peripheral blood stem cell transplant: phase II study. Bone Marrow Transplant 2005; 35: 1165–1169.

    Article  CAS  PubMed  Google Scholar 

  51. Martino M, Pratico G, Messina G, Irrera G, Massara E, Messina G et al. Pegfilgrastim compared with filgrastim after high-dose melphalan and autologous hematopoietic peripheral blood stem cell transplantation in multiple myeloma patients. Eur J Haematol 2006; 77: 410–415.

    Article  CAS  PubMed  Google Scholar 

  52. Vanstraelen G, Frere P, Ngirabacu MC, Willems E, Fillet G, Beguin Y . Pegfilgrastim compared with Filgrastim after autologous hematopoietic peripheral blood stem cell transplantation. Exp Hematol 2006; 34: 382–388.

    Article  CAS  PubMed  Google Scholar 

  53. Ballestrero A, Boy D, Gonella R, Miglino M, Clavio M, Barbero V et al. Pegfilgrastim compared with filgrastim after autologous peripheral blood stem cell transplantation in patients with solid tumours and lymphomas. Ann Hematol 2008; 87: 49–55.

    Article  PubMed  Google Scholar 

  54. Gerds A, Fox-Geiman M, Dawravoo K, Rodriguez T, Toor A, Smith S et al. A Phase III, randomized, placebo-controlled comparative trial of pegfilgrastim versus filgrastim after autologous stem cell transplantation(PBPSCT). Blood 2007; 110: 479.

    Article  Google Scholar 

  55. Rader M . Granulocyte colony-stimulating factor use in patients with chemotherapy-induced neutropenia: clinical and economic benefits. Oncology (Williston Park) 2006; 20: 16–21.

    Google Scholar 

  56. Numnum TM, Kimball KJ, Rocconi RP, Kilgore LC, Straughn Jr JM . Pegfilgrastim for the prevention of febrile neutropenia in patients with epithelial ovarian carcinoma—a cost-effectiveness analysis. Int J Gynecol Cancer 2007; 17: 1019–1024.

    Article  CAS  PubMed  Google Scholar 

  57. Eldar-Lissai A, Cosler LE, Culakova E, Lyman GH . Economic analysis of prophylactic pegfilgrastim in adult cancer patients receiving chemotherapy. Value Health 2008; 11: 172–179.

    Article  PubMed  Google Scholar 

  58. Ng R, Green MD . Pegfilgrastim: evidence in support of its use with cytotoxic chemotherapy. Expert Rev Anticancer Ther 2005; 5: 585–590.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to G Kobbe.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kobbe, G., Bruns, I., Fenk, R. et al. Pegfilgrastim for PBSC mobilization and autologous haematopoietic SCT. Bone Marrow Transplant 43, 669–677 (2009). https://doi.org/10.1038/bmt.2009.59

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2009.59

Keywords

This article is cited by

Search

Quick links