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:

Autografting

Thiotepa, busulfan, cyclophosphamide (TBC) and autologous hematopoietic transplantation: an intensive regimen for the treatment of multiple myeloma

Abstract

The study was designed to evaluate the efficacy and safety of an intensive, tri-alkylator conditioning regimen, consisting of thiotepa, busulfan and cyclophosphamide (TBC), prior to autologous hematopoietic cell transplantation in patients with multiple myeloma (MM) and to analyze factors associated with outcome. One hundred and twenty patients with MM received high-dose chemotherapy with TBC followed by autologous bone marrow (n = 24) or peripheral blood stem cell (PBSC) transplantation (n = 96). Fifty-four patients had chemosensitive disease and 66 had refractory disease at the time of transplantation. The overall response rate was 81% and the complete remission (CR) rate was 26%. Patients with chemosensitive disease had a CR rate of 52% vs 5% for patients with refractory disease. Multivariable analysis determined disease status at transplant as the factor most likely associated with long survival. Estimated median survival was 48, 35 and 9 months for patients with chemosensitive, primary refractory or disease in refractory relapse, respectively. Short interval from diagnosis to transplant among patients with primary refractory disease and younger age were also favorable prognostic factors for survival. Patients with refractory disease pre-transplant who achieved remission criteria rapidly after treatment had a worse outcome than the slow responders. Treatment-related mortality with the introduction of PBSC and better supportive care was 4.8%. In conclusion, TBC is an effective and relatively well-tolerated intensive conditioning regimen in patients with MM. A more favorable outcome was observed in patients with chemosensitive disease and with early treatment for primary refractory disease. TBC merits further study in these subgroups and comparison with alternative regimens in prospective studies is warranted. Bone Marrow Transplantation (2001) 27, 821–828.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Alexanian R, Dimopoulos M . The treatment of multiple myeloma New Engl J Med 1994 330: 484–489

    Article  CAS  PubMed  Google Scholar 

  2. Kyle RA . Prognostic factors in multiple myeloma Stem Cells 1995 13: (Suppl. 2) 56–63

    PubMed  Google Scholar 

  3. Attal M, Harousseau J, Stoppa A et al. A prospective randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma New Engl J Med 1996 335: 91–97

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  5. Harousseau J, Attal M, Divine M et al. Autologous stem cell transplantation after first remission induction treatment in multiple myeloma: a report of the French registry on autologous transplantation in multiple myeloma Blood 1995 85: 3077–3085

    CAS  PubMed  Google Scholar 

  6. Barlogie B, Jagannath S, Naucke S et al. Long term follow-up after therapy for high risk multiple myeloma Bone Marrow Transplant 1998 21: 1101–1107

    Article  CAS  PubMed  Google Scholar 

  7. Vesole DH, Crowly JJ, Catchatourian R . High-dose melphalan with autotransplantation for refractory multiple myeloma: results of a Southwest Oncology Group phase II trial J Clin Oncol 1999 17: 2173–2179

    Article  CAS  PubMed  Google Scholar 

  8. Barlogie B, Desikar R, Munshi M et al. Durable CR in multiple myeloma in the absence of chromosome 13 deletion and with tandem, melphalan-based, high-dose therapy. The Arkansas experience with 1000 consecutive patients Blood 1999 94: (Suppl. 1) 714 (Abstr.)

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  10. Attal M, Harousseau JL, Stoppa AM et al. High dose therapy in multiple myeloma: an update analysis of the IFM 90 protocol Blood 1997 90: (Suppl. 1) 418 (Abstr.)

    Google Scholar 

  11. 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 

  12. Alexanian R, Dimopoulos MA, Delasalle KB et al. Myeloablative therapy for primary resistant myeloma Stem Cells 1995 13: (Suppl. 2) 118–121

    Article  PubMed  Google Scholar 

  13. Alexanian R, Dimopoulos M, Smith T et al. Limited value of myeloablative therapy in late multiple myeloma Blood 1994 83: 512–516

    CAS  PubMed  Google Scholar 

  14. Dimopoulos MA, Alexanian R, Przepiorka D et al. Thiotepa, busulfan and cyclophosphamide: a new preparative regimen for autologous marrow or blood stem cell transplantation in high risk multiple myeloma Blood 1993 82: 2324–2328

    CAS  PubMed  Google Scholar 

  15. Vesole DH, Barlogie B, Jagannath S et al. High dose therapy for refractory myeloma: improved prognosis with better supportive care and double transplants Blood 1994 84: 950–956

    CAS  PubMed  Google Scholar 

  16. Powles R, Raje N, Millar B et al. Outcome assessment of a population-based group of 195 unselected myeloma patients under 70 years of age offered intensive treatment Bone Marrow Transplant 1997 20: 435–443

    Article  CAS  PubMed  Google Scholar 

  17. Jagannath S, Barlogie B, Dicke K et al. Autologous bone marrow transplantation in multiple myeloma – identification of prognostic factors Blood 1990 76: 1860–1866

    CAS  PubMed  Google Scholar 

  18. Rajkumar SV, Fonseca R, Lacy MQ et al. Autotologous stem cell transplantation for relapsed and primary refractory myeloma Bone Marrow Transplant 1999 23: 1267–1272

    Article  CAS  PubMed  Google Scholar 

  19. Rajkumar SV, Fonseca R, Lacy MQ et al. Plasmablastic morphology is an independent predictor of poor survival after autologous stem-cell transplantation for multiple myeloma J Clin Oncol 1999 17: 1551–1557

    Article  CAS  PubMed  Google Scholar 

  20. McLaughlin P, Alexanian R . Myeloma protein kinetics following chemotherapy Blood 1982 60: 851–855

    CAS  PubMed  Google Scholar 

  21. Boccadoro M, Marmont F, Tribalto M et al. Early responder myeloma: kinetic studies identify a patient subgroup characterized by very poor prognosis J Clin Oncol 1989 7: 119–125

    Article  CAS  PubMed  Google Scholar 

  22. Bearman SI, Appelbaum FR, Buckner CD et al. Regimen related toxicities in patients undergoing bone marrow transplantation J Clin Oncol 1988 6: 1562–1568

    Article  CAS  PubMed  Google Scholar 

  23. Durie BG, 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 

  24. Dimopoulos MA, Delasalle KB, Champlin R et al. Cyclophosphamide and etoposide therapy with GM-CSF for VAD-resistant multiple myeloma Br J Haematol 1993 83: 240–244

    Article  CAS  PubMed  Google Scholar 

  25. Dimopoulos MA, Weber D, Kantarjian H et al. HyperCVAD for VAD-resistant multiple myeloma Am J Hematol 1996 52: 77–81

    Article  CAS  PubMed  Google Scholar 

  26. Giralt S, Weber D, Colome M et al. Phase I study of cyclosporine-induce graft versus host disease in patients with multiple myeloma undergoing high dose chemotherapy with autologous stem cell rescue J Clin Oncol 1997 15: 667–673

    Article  CAS  PubMed  Google Scholar 

  27. 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 hematopoietic stem cell transplantation Br J Haematol 1998 102: 1115–1123

    Article  CAS  PubMed  Google Scholar 

  28. Kaplan EL, Meier P . Nonparametric estimation from incomplete observation J Am Stat Assoc 1958 53: 457–481

    Article  Google Scholar 

  29. Steinberg D, Colla P . CART: Tree-structured Non-parametric Data Analysis Salford Systems: San Diego, CA 1995

    Google Scholar 

  30. Cox DR . Regression models and life tables J R Stat Soc 1972 34: 187–220

    Google Scholar 

  31. Siegel DS, Desikan KR, Mehta J et al. Age is not a prognostic variable with autotransplants for multiple myeloma Blood 1999 93: 51–54

    CAS  PubMed  Google Scholar 

  32. Singhal S, Powles R, Milan S et al. Kinetics of paraprotein clearance after autografting for multiple myeloma Bone Marrow Transplant 1995 16: 537–540

    CAS  PubMed  Google Scholar 

  33. Gore ME, Selby PJ, Clark PI et al. Intensive treatment of multiple myeloma and criteria for complete response Lancet 1989 2: 879–882

    Article  CAS  PubMed  Google Scholar 

  34. Cunningham D, Paz-Ares L, Milan S et al. High dose melphalan and autologous bone marrow transplantation as consolidation in previously untreated myeloma J Clin Oncol 1994 12: 759–763

    Article  CAS  PubMed  Google Scholar 

  35. Takahashi T, Lim B, Jamal N et al. Colony growth and self-renewal of plasma cell precursors in multiple myeloma J Clin Oncol 1985 3: 1613–1623

    Article  CAS  PubMed  Google Scholar 

  36. Hansen OP, Jessen B, Videbaek A . Prognosis of myelomatosis on treatment with prednisone and cytostatics Scand J Haematol 1973 10: 282–290

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shimoni, A., Smith, T., Aleman, A. et al. Thiotepa, busulfan, cyclophosphamide (TBC) and autologous hematopoietic transplantation: an intensive regimen for the treatment of multiple myeloma. Bone Marrow Transplant 27, 821–828 (2001). https://doi.org/10.1038/sj.bmt.1703007

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1703007

Keywords

This article is cited by

Search

Quick links