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:

Cell Procurement

Comparison of high-dose CY and growth factor with growth factor alone for mobilization of stem cells for transplantation in patients with multiple myeloma

Bone Marrow Transplantation volume 43, pages 619–625 (2009)Cite this article

Abstract

We retrospectively analyzed outcomes of 716 patients with multiple myeloma who were mobilized using CY and growth factor (n=370) or growth factor alone (n=346) before SCT. Patients receiving CY had higher stem cell yields than the growth factor only group (median number of apheresis sessions needed to achieve stem cell collection goals, two vs four sessions, respectively (P=0.001)). However, patients treated with CY required more time for engraftment of platelets and neutrophils (P<0.001 for both). For patients receiving CY, 75% achieved engraftment (defined as a platelet count of 50 × 109/l) by day 39, whereas 75% of patients not receiving CY achieved engraftment by day 18. Similar results were observed for neutrophil engraftment. These differences did not affect the duration of hospitalization, but patients treated with CY had a higher incidence of post transplant nonstaphylococcal bacteremia. For CY-mobilized patients, considerably faster platelet engraftment (5 fewer days) resulted if stem cell reinfusion occurred more than 30 days after the first apheresis session. Our data suggested that CY damaged the microenvironment and slowed engraftment. By lengthening the period between the completion of apheresis and stem cell reinfusion, the microenvironment may recover and result in faster engraftment.

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
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Bjorkstrand B, Gahrton G . High-dose treatment with autologous stem cell transplantation in multiple myeloma: past, present, and future. Semin Hematol 2007; 44: 227–233.

    Article  PubMed  Google Scholar 

  2. Jagannath S . Current standards for first-line therapy of multiple myeloma. Clin Lymphoma Myeloma 2007; 7 (Suppl 5): S207–S214.

    Article  CAS  PubMed  Google Scholar 

  3. Bashey A, Donohue M, Liu L, Medina B, Corringham S, Ihasz A et al. Peripheral blood progenitor cell mobilization with intermediate-dose cyclophosphamide, sequential granulocyte-macrophage-colony-stimulating factor and granulocyte-colony-stimulating factor, and scheduled commencement of leukapheresis in 225 patients undergoing autologous transplantation. Transfusion 2007; 47: 2153–2160.

    Article  PubMed  Google Scholar 

  4. 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 

  5. Goldschmidt H, Hegenbart U, Haas R, Hunstein W . Mobilization of peripheral blood progenitor cells with high-dose cyclophosphamide (4 or 7 g/m2) and granulocyte colony-stimulating factor in patients with multiple myeloma. Bone Marrow Transplant 1996; 17: 691–697.

    CAS  PubMed  Google Scholar 

  6. To LB, Shepperd KM, Haylock DN, Dyson PG, Charles P, Thorp DL et al. Single high doses of cyclophosphamide enable the collection of high numbers of hemopoietic stem cells from the peripheral blood. Exp Hematol 1990; 18: 442–447.

    CAS  PubMed  Google Scholar 

  7. Boiron JM, Marit G, Faberes C, Cony-Makhoul P, Foures C, Ferrer AM et al. Collection of peripheral blood stem cells in multiple myeloma following single high-dose cyclophosphamide with and without recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Bone Marrow Transplant 1993; 12: 49–55.

    CAS  PubMed  Google Scholar 

  8. Vescio RA, Han EJ, Schiller GJ, Lee JC, Wu CH, Cao J et al. Quantitative comparison of multiple myeloma tumor contamination in bone marrow harvest and leukapheresis autografts. Bone Marrow Transplant 1996; 18: 103–110.

    CAS  PubMed  Google Scholar 

  9. Vescio R, Schiller G, Stewart AK, Ballester O, Noga S, Rugo H et al. Multicenter phase III trial to evaluate CD34+ selected versus unselected autologous peripheral blood progenitor cell transplantation in multiple myeloma. Blood 1999; 93: 1858–1868.

    CAS  PubMed  Google Scholar 

  10. Stewart AK, Vescio R, Schiller G, Ballester O, Noga S, Rugo H et al. Purging of autologous peripheral-blood stem cells using CD34 selection does not improve overall or progression-free survival after high-dose chemotherapy for multiple myeloma: results of a multicenter randomized controlled trial. J Clin Oncol 2001; 19: 3771–3779.

    Article  CAS  PubMed  Google Scholar 

  11. Hill QA, Buxton D, Pearce R, Gesinde MO, Smith GM, Cook G . An analysis of the optimal timing of peripheral blood stem cell harvesting following priming with cyclophosphamide and G-CSF. Bone Marrow Transplant 2007; 40: 925–930.

    Article  CAS  PubMed  Google Scholar 

  12. Kumar S, Lacy MQ, Dispenzieri A, Rajkumar SV, Fonseca R, Geyer S et al. High-dose therapy and autologous stem cell transplantation for multiple myeloma poorly responsive to initial therapy. Bone Marrow Transplant 2004; 34: 161–167.

    Article  CAS  PubMed  Google Scholar 

  13. Dingli D, Nowakowski GS, Dispenzieri A, Lacy MQ, Hayman S, Litzow MR et al. Cyclophosphamide mobilization does not improve outcome in patients receiving stem cell transplantation for multiple myeloma. Clin Lymphoma Myeloma 2006; 6: 384–388.

    Article  CAS  PubMed  Google Scholar 

  14. Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Kumar S, Leung N et al. Impact of age and serum creatinine value on outcome after autologous blood stem cell transplantation for patients with multiple myeloma. Bone Marrow Transplant 2007; 39: 605–611.

    Article  CAS  PubMed  Google Scholar 

  15. Croockewit A, Raymakers RA, Trilsbeek C, Dolstra H, Pennings A, De Witte TJ et al. Peripheral blood cell harvests yield primitive multilineage progenitor cells in the CD34+/33− fraction. Int J Artif Organs 1993; 16 (Suppl 5): 83–88.

    Article  PubMed  Google Scholar 

  16. Burgstaler EA, Pineda AA, Winters JL . Hematopoietic progenitor cell large volume leukapheresis (LVL) on the Fenwal Amicus blood separator. J Clin Apher 2004; 19: 103–111.

    Article  PubMed  Google Scholar 

  17. 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 

  18. Desikan KR, Tricot G, Munshi NC, Anaissie E, Spoon D, Fassas A et al. Preceding chemotherapy, tumour load and age influence engraftment in multiple myeloma patients mobilized with granulocyte colony-stimulating factor alone. Br J Haematol 2001; 112: 242–247.

    Article  CAS  PubMed  Google Scholar 

  19. Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Gastineau DA et al. Impact of lenalidomide therapy on stem cell mobilization and engraftment post-peripheral blood stem cell transplantation in patients with newly diagnosed myeloma. Leukemia 2007; 21: 2035–2042.

    Article  CAS  PubMed  Google Scholar 

  20. Paripati H, Stewart AK, Cabou S, Dueck A, Zepeda VJ, Pirooz N et al. Compromised stem cell mobilization following induction therapy with lenalidomide in myeloma. Leukemia 2008; 22: 1282–1284.

    Article  CAS  PubMed  Google Scholar 

  21. Dyson PG, Horvath N, Joshua D, Barrow L, Van Holst NG, Brown R et al. CD34+ selection of autologous peripheral blood stem cells for transplantation following sequential cycles of high-dose therapy and mobilization in multiple myeloma. Bone Marrow Transplant 2000; 25: 1175–1184.

    Article  CAS  PubMed  Google Scholar 

  22. Tricot G, Jagannath S, Vesole D, Nelson J, Tindle S, Miller L 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 

  23. Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Kumar SK . High-dose chemotherapy with autologous hematopoietic stem cell transplantation in patients with multiple myeloma. Expert Rev Anticancer Ther 2006; 6: 343–360.

    Article  CAS  PubMed  Google Scholar 

  24. Alegre A, Tomas JF, Martinez-Chamorro C, Gil-Fernandez JJ, Fernandez-Villalta MJ, Arranz R et al. Comparison of peripheral blood progenitor cell mobilization in patients with multiple myeloma: high-dose cyclophosphamide plus GM-CSF vs G-CSF alone. Bone Marrow Transplant 1997; 20: 211–217.

    Article  CAS  PubMed  Google Scholar 

  25. Mazumder A, Kaufman J, Niesvizky R, Lonial S, Vesole D, Jagannath S . Effect of lenalidomide therapy on mobilization of peripheral blood stem cells in previously untreated multiple myeloma patients. Leukemia 2008; 22: 1280–1281; author reply 1281–2.

    Article  CAS  PubMed  Google Scholar 

  26. Tarella C, Boccadoro M, Omede P, Bondesan P, Caracciolo D, Frieri R et al. Role of chemotherapy and GM-CSF on hemopoietic progenitor cell mobilization in multiple myeloma. Bone Marrow Transplant 1993; 11: 271–277.

    CAS  PubMed  Google Scholar 

  27. Scott MA, Ager S, Apperley JF, Jestice HK, Bloxham DM, Boraks P et al. Peripheral blood progenitor cell harvesting in multiple myeloma and malignant lymphoma. Leuk Lymphoma 1995; 19: 479–484.

    Article  CAS  PubMed  Google Scholar 

  28. Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Kumar SK, Leung N et al. Transplantation without growth factor: engraftment kinetics after stem cell transplantation for primary systemic amyloidosis (AL). Bone Marrow Transplant 2007; 40: 989–993.

    Article  CAS  PubMed  Google Scholar 

  29. Narayanasami U, Kanteti R, Morelli J, Klekar A, Al-Olama A, Keating C et al. Randomized trial of filgrastim versus chemotherapy and filgrastim mobilization of hematopoietic progenitor cells for rescue in autologous transplantation. Blood 2001; 98: 2059–2064.

    Article  CAS  PubMed  Google Scholar 

  30. Galotto M, Berisso G, Delfino L, Podesta M, Ottaggio L, Dallorso S et al. Stromal damage as consequence of high-dose chemo/radiotherapy in bone marrow transplant recipients. Exp Hematol 1999; 27: 1460–1466.

    Article  CAS  PubMed  Google Scholar 

  31. Banfi A, Bianchi G, Galotto M, Cancedda R, Quarto R . Bone marrow stromal damage after chemo/radiotherapy: occurrence, consequences and possibilities of treatment. Leuk Lymphoma 2001; 42: 863–870.

    Article  CAS  PubMed  Google Scholar 

  32. Corazza F, Hermans C, Ferster A, Fondu P, Demulder A, Sariban E . Bone marrow stroma damage induced by chemotherapy for acute lymphoblastic leukemia in children. Pediatr Res 2004; 55: 152–158.

    Article  PubMed  Google Scholar 

  33. Li J, Law HK, Lau YL, Chan GC . Differential damage and recovery of human mesenchymal stem cells after exposure to chemotherapeutic agents. Br J Haematol 2004; 127: 326–334.

    Article  CAS  PubMed  Google Scholar 

  34. Kushner BH, Gulati SC, O'Reilly RJ, Heller G, Cheung NK . Autografting with bone marrow exposed to multiple courses of very high dose cyclophosphamide in vivo and to 4-hydroperoxycyclophosphamide in vitro. Med Pediatr Oncol 1990; 18: 454–458.

    Article  CAS  PubMed  Google Scholar 

  35. Spyridonidis A, Kuttler T, Wasch R, Samek E, Waterhouse M, Behringer D et al. Reduced intensity conditioning compared to standard conditioning preserves the in vitro growth capacity of bone marrow stroma, which remains of host origin. Stem Cells Dev 2005; 14: 213–222.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    M A Gertz, S K Kumar, M Q Lacy, A Dispenzieri, S R Hayman, F K Buadi, D Dingli, D A Gastineau & M R Litzow

  2. Division of Transfusion Medicine, Mayo Clinic, Rochester, MN, USA

    J L Winters

Authors
  1. M A Gertz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S K Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Q Lacy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A Dispenzieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S R Hayman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F K Buadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. D Dingli
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. D A Gastineau
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J L Winters
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M R Litzow
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M A Gertz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gertz, M., Kumar, S., Lacy, M. et al. Comparison of high-dose CY and growth factor with growth factor alone for mobilization of stem cells for transplantation in patients with multiple myeloma. Bone Marrow Transplant 43, 619–625 (2009). https://doi.org/10.1038/bmt.2008.369

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2008.369

Keywords

This article is cited by

Search

Advanced search

Quick links