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:

Myelofibrosis

A new conditioning regimen involving total marrow irradiation, busulfan and cyclophosphamide followed by autologous PBSCT in patients with advanced multiple myeloma

Bone Marrow Transplantation volume 32, pages 593–599 (2003)Cite this article

Summary:

The overall survival of patients with advanced multiple myeloma (MM) undergoing high-dose chemotherapy and autologous stem cell transplantation (SCT) depends mainly on the quality of response. Thus, to improve the response rate, a new intensified high-dose chemoradiotherapy was evaluated in a phase I/II study. After induction chemotherapy, 89 patients (median age 51 years, range 32–60 years) with MM stage II/III received a conditioning regimen with total marrow irradiation (9 Gy), busulfan (12 mg/kg) and cyclophosphamide (120 mg/kg) followed by SCT. Regimen-related toxicity according to WHO criteria and response rates defined by EBMT/IBMTR were analyzed. The main toxicity was mucositis grade III/IV in 76%, and fever grade >I in 75% of patients. Three patients developed reversible veno-occlusive disease. Transplant-related mortality was 2%. Among patients with de novo and pretreated MM, a CR rate of 48 and 41%, respectively, was documented. With a median follow-up of 45 months, the actuarial median durations of event-free survival (EFS) and overall survival (OS) after transplant were 29 and 61 months for the whole group, 36 and 85 months for patients with de novo MM, respectively. Thus, administration of this intensified conditioning regimen was associated with tolerable toxicity, a high response rate and long EFS and OS.

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

Similar content being viewed by others

References

  1. Boccadoro M, Pileri A . Diagnosis, prognosis, and standard treatment of multiple myeloma. Clin Haematol Oncol N Am 1997; 11: 111–131.

    Article  CAS  Google Scholar 

  2. Barlogie B . Plasma cell myeloma. In: Kipps T (ed.). Haematology. William's Haematology, 5th edn. McGraw-Hill: Baltimore, MD, 1995, pp 1109–1130.

    Google Scholar 

  3. Boccadoro M, Marmont F, Tribalto M et al. Multiple myeloma: VMCP/VBAP alternating combination chemotherapy is not superior to melphalan and prednisone even in high-risk patients. J Clin Oncol 1991; 9: 444–448.

    Article  CAS  PubMed  Google Scholar 

  4. McElwain TJ, Powles RJ . High-dose intravenous melphalan for plasma-cell leukaemia and myeloma. Lancet 1983; 2: 822–824.

    Article  CAS  PubMed  Google Scholar 

  5. Fefer A, Cheever MA, Greenberg PD . Identical-twin (syngeneic) marrow transplantation for haematologic cancers. J Natl Cancer Inst 1986; 76: 1269–1273.

    CAS  PubMed  Google Scholar 

  6. Barlogie B, Hall R, Zander A et al. High-dose melphalan with autologous bone marrow transplantation for multiple myeloma. Blood 1986; 67: 1298–1301.

    CAS  PubMed  Google Scholar 

  7. Fermand JP, Levy Y, Gerota J et al. Treatment of aggressive multiple myeloma by high-dose chemotherapy and total body irradiation followed by blood stem cells autologous graft. Blood 1989; 73: 20–23.

    CAS  PubMed  Google Scholar 

  8. Alexanian R, Dimopoulos MA, Hester J et al. Early myeloablative therapy for multiple myeloma. Blood 1994; 84: 4278–4282.

    CAS  PubMed  Google Scholar 

  9. Attal M, Harousseau JL, Stoppa AM et al. A prospective, randomised trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma, Intergroupe Francais du Myelome. N Engl J Med 1996; 335: 91–97.

    Article  CAS  PubMed  Google Scholar 

  10. Barlogie B, Jagannath S, Vesole DH et al. Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma. Blood 1997; 89: 789–793.

    CAS  PubMed  Google Scholar 

  11. Lenhoff S, Hjorth M, Holmberg E et al. Impact on survival of high-dose therapy with autologous stem cell support in patients younger than 60 years with newly diagnosed multiple myeloma: a population-based study. Blood 2000; 95: 7–11.

    CAS  PubMed  Google Scholar 

  12. Petersen FB, Buckner CD, Appelbaum FR et al. Busulfan, cyclophosphamide and fractionated total body irradiation as a preparatory regimen for marrow transplantation in patients with advanced haematological malignancies: a phase I study. Bone Marrow Transplant 1989; 4: 617–623.

    CAS  PubMed  Google Scholar 

  13. Lynch MH, Petersen FB, Appelbaum FR et al. Phase II study of busulfan, cyclophosphamide and fractionated total body irradiation as a preparatory regimen for allogeneic bone marrow transplantation in patients with advanced myeloid malignancies. Bone Marrow Transplant 1995; 15: 59–64.

    PubMed  Google Scholar 

  14. Bensinger WI, Rowley SD, Demirer T et al. High-dose therapy followed by autologous haematopoietic stem-cell infusion for patients with multiple myeloma. J Clin Oncol 1996; 5: 1447–1456.

    Article  Google Scholar 

  15. Durie BGM, Salmon S . A clinical staging system for multiple myeloma, Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer 1975; 36: 842–854.

    Article  CAS  PubMed  Google Scholar 

  16. Blade J, Samson D, Reece D et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. Br J Haematol 1998; 102: 1115–1123.

    Article  CAS  PubMed  Google Scholar 

  17. Keys A, Fidanza F, Karvonen MJ et al. Indices of relative weight and obesity. J Chronic Dis 1972; 25: 329–343.

    Article  CAS  PubMed  Google Scholar 

  18. Tarella C, Caracciolo D, Gavarotti P et al. Overweight as an adverse prognostic factor for non-Hodgkin's lymphoma patients receiving high-dose chemotherapy and autograft. Bone Marrow Transplant 2000; 26: 1185–1191.

    Article  CAS  PubMed  Google Scholar 

  19. Vesole DH, Tricot G, Jagannath S et al. Autotransplants in multiple myeloma: what have we learned? Blood 1996; 88: 838–847.

    CAS  PubMed  Google Scholar 

  20. Weaver CH, Zhen B, Schwartzberg LS et al. Phase I–II evaluation of rapid sequence tandem high-dose melphalan with peripheral blood stem cell support in patients with multiple myeloma. Bone Marrow Transplant 1998; 22: 245–251.

    Article  CAS  PubMed  Google Scholar 

  21. Jagannath S, Vesole DH, Glenn L et al. Low-risk intensive therapy for multiple myeloma with combined autologous bone marrow and blood stem cell support. Blood 1992; 80: 1666–1672.

    CAS  PubMed  Google Scholar 

  22. Cunningham D, Paz-Ares L, Gore ME et al. High-dose melphalan for multiple myeloma: long term follow-up data. J Clin Oncol 1994; 12: 764–768.

    Article  CAS  PubMed  Google Scholar 

  23. Fermand JP, Chevret S, Ravaud P et al. High-dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma: results of a phase II trial involving 63 patients. Blood 1993; 82: 2005–2009.

    CAS  PubMed  Google Scholar 

  24. Goldschmidt H, Hegenbart U, Wallmeier M et al. Peripheral blood progenitor cell transplantation in multiple myeloma following high-dose melphalan-based therapy. Recent Res Clin Cancer 1998; 144: 27–35.

    Article  CAS  Google Scholar 

  25. Desikan KR, Tricot G, Dhodapkar M et al. Melphalan plus total body irradiation (MEL-TBI) or cyclophosphamide (MEL-CY) as a conditioning regimen with second autotransplant in responding patients with myeloma is inferior compared to historical controls receiving tandem transplants with melphalan alone. Bone Marrow Transplant 2000; 25: 483–487.

    Article  CAS  PubMed  Google Scholar 

  26. Moreau P, Facon T, Attal M et al. Comparison of 200 mg/m2 melphalan and 8 Gy total body irradiation plus 140 mg/m2 melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myelome 9502 randomized trial. Blood 2002; 99: 731–735.

    Article  CAS  PubMed  Google Scholar 

  27. Lehnert S, Greene D, Batist G . Radiation resistance in a melphalan-resistant subline of a rat mammary carcinoma. Radiat Res 1994; 139: 232–239.

    Article  CAS  PubMed  Google Scholar 

  28. Louie KG, Behrens BC, Kinsella TJ et al. Radiation survival parameters of antineoplastic drug-sensitive and -resistant human ovarian cancer cell lines and their modification by buthionine sulfoximine. Cancer Res 1985; 45: 2110–2115.

    CAS  PubMed  Google Scholar 

  29. Barlogie B, Jagannath S, Desikan KR et al. Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood 1999; 93: 55–65.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant by the Deutsche Forschungsgemeinschaft (SFB 120 project B1), by the Jose Carreras Foundation Against Leukemia and the National Institutes of Health Grant CA 47748.

Author information

Authors and Affiliations

  1. Department of Hematology and Oncology, Tübingen, Germany

    H Einsele, H Hebart, H Schmidt & L Kanz

  2. Department for Radiotherapy, Tübingen, Germany

    M Bamberg & W Budach

  3. Department of Radiotherapy, Göttingen, Germany

    H Schmidberger & C F Hess

  4. Department of Hematology and Oncology, Göttingen, Germany

    B Wörmann

  5. Institute for Medical Information Processing, Tübingen, Germany

    C Meisner

  6. Department of Hematology, City-Hospital, München, Germany

    C Straka

  7. Department of Hematology/Oncology, Homburg, Germany

    L Trümper

  8. Department of Hematology/Oncology, Hamburg, Germany

    N Kröger, A R Zander, S Hegewisch-Becker & D K Hossfeld

  9. Department of Hematology/Oncology, Augsburg, Germany

    P Müller & G Schlimok

  10. Department of Hematology/Oncology, Hannover, Germany

    B Hertenstein & D Peest

  11. Department of Hematology/Oncology, Oldenburg, Germany

    B Metzner

  12. Department of Hematology/Oncology, Ulm, Germany

    N Frickhofen

  13. Fred-Hutchinson Cancer Research Center, Seattle, WA, USA

    W I Bensinger

Authors
  1. H Einsele
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Bamberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W Budach
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H Schmidberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C F Hess
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B Wörmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C Meisner
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C Straka
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. H Hebart
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. L Trümper
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. N Kröger
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. A R Zander
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. S Hegewisch-Becker
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. D K Hossfeld
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. H Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. P Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. G Schlimok
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. B Hertenstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. D Peest
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. B Metzner
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. N Frickhofen
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. L Kanz
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. W I Bensinger
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Einsele, H., Bamberg, M., Budach, W. et al. A new conditioning regimen involving total marrow irradiation, busulfan and cyclophosphamide followed by autologous PBSCT in patients with advanced multiple myeloma. Bone Marrow Transplant 32, 593–599 (2003). https://doi.org/10.1038/sj.bmt.1704192

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704192

Keywords

This article is cited by

Search

Advanced search

Quick links