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

Tandem autologous vs autologous plus reduced intensity allogeneic transplantation in the upfront management of multiple myeloma: meta-analysis of trials with biological assignment

Bone Marrow Transplantation volume 48, pages 562–567 (2013)Cite this article

Subjects

Abstract

We utilized meta-analysis to compare tandem autologous (TA) hematopoietic SCT (auto-HSCT) or single auto-HSCT followed by reduced intensity conditioning (RIC), allogeneic (AR) hematopoietic SCT in the upfront management of patients with multiple myeloma (MM). A comprehensive search strategy of published and unpublished reports utilized the following entry criteria: newly diagnosed patients, first autologous transplantation in both arms, use of an RIC regimen and assignment to TA or AR based exclusively on the availability of an HLA matched donor. Six trials were identified yielding 1192 subjects in TA and 630 in AR. Patients in AR had higher likelihoods of TRM (relative risk (RR)=3.3, 95% confidence interval (CI)=2.2–4.8) and CR (RR=1.4, 95% CI=1.1–1.8). OS was not different in the first 36 months (hazard ratio (HR)=1.15, 95% CI=0.91–1.45) or after (HR=0.74, 95% CI=0.53–1.04) 36 months from assignment. Similar findings were seen for PFS. When compared with TA in the upfront management of MM, AR is associated with higher TRM and CR without improvement in PFS or 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
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF et al. A prospective, randomized 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 

  2. Fermand JP, Ravaud P, Chevret S, Divine M, Leblond V, Belanger C et al. High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial. Blood 1998; 92: 3131–3136.

    CAS  PubMed  Google Scholar 

  3. Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003; 348: 1875–1883.

    CAS  PubMed  Google Scholar 

  4. Blade J, Rosinol L, Sureda A, Ribera JM, Diaz-Mediavilla J, Garcia-Larana J et al. High-dose therapy intensification compared with continued standard chemotherapy in multiple myeloma patients responding to the initial chemotherapy: long-term results from a prospective randomized trial from the Spanish cooperative group PETHEMA. Blood 2005; 106: 3755–3759.

    CAS  PubMed  Google Scholar 

  5. Barlogie B, Kyle RA, Anderson KC, Greipp PR, Lazarus HM, Hurd DD et al. Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US Intergroup Trial S9321. J Clin Oncol 2006; 24: 929–936.

    Article  CAS  PubMed  Google Scholar 

  6. 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 

  7. Cavo M, Tosi P, Zamagni E, Cellini C, Tacchetti P, Patriarca F et al. Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 clinical study. J Clin Oncol 2007; 25: 2434–2441.

    Article  PubMed  Google Scholar 

  8. Tricot G, Vesole DH, Jagannath S, Hilton J, Munshi N, Barlogie B . Graft-versus-myeloma effect: proof of principle. Blood 1996; 87: 1196–1198.

    CAS  PubMed  Google Scholar 

  9. Lokhorst HM, Schattenberg A, Cornelissen JJ, van Oers MH, Fibbe W, Russell I et al. Donor lymphocyte infusions for relapsed multiple myeloma after allogeneic stem-cell transplantation: predictive factors for response and long-term outcome. J Clin Oncol 2000; 18: 3031–3037.

    Article  CAS  PubMed  Google Scholar 

  10. Lokhorst HM, Wu K, Verdonck LF, Laterveer LL, van de Donk NW, van Oers MH et al. The occurrence of graft-versus-host disease is the major predictive factor for response to donor lymphocyte infusions in multiple myeloma. Blood 2004; 103: 4362–4364.

    Article  CAS  PubMed  Google Scholar 

  11. Gahrton G, Tura S, Ljungman P, Belanger C, Brandt L, Cavo M et al. Allogeneic bone marrow transplantation in multiple myeloma. European Group for Bone Marrow Transplantation. N Engl J Med 1991; 325: 1267–1273.

    Article  CAS  PubMed  Google Scholar 

  12. Gahrton G, Svensson H, Cavo M, Apperly J, Bacigalupo A, Bjorkstrand B et al. Progress in allogenic bone marrow and peripheral blood stem cell transplantation for multiple myeloma: a comparison between transplants performed 1983–93 and 1994–8 at European Group for Blood and Marrow Transplantation centres. Br J Haematol 2001; 113: 209–216.

    Article  CAS  PubMed  Google Scholar 

  13. Kroger N, Schwerdtfeger R, Kiehl M, Sayer HG, Renges H, Zabelina T et al. Autologous stem cell transplantation followed by a dose-reduced allograft induces high complete remission rate in multiple myeloma. Blood 2002; 100: 755–760.

    Article  CAS  PubMed  Google Scholar 

  14. Maloney DG, Molina AJ, Sahebi F, Stockerl-Goldstein KE, Sandmaier BM, Bensinger W et al. Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma. Blood 2003; 102: 3447–3454.

    Article  CAS  PubMed  Google Scholar 

  15. Giralt S, Ballen K, Rizzo D, Bacigalupo A, Horowitz M, Pasquini M et al. Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant 2009; 15: 367–369.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Parmar MK, Torri V, Stewart L . Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 1998; 17: 2815–2834.

    Article  CAS  PubMed  Google Scholar 

  17. Bjorkstrand B, Iacobelli S, Hegenbart U, Gruber A, Greinix H, Volin L et al. Tandem autologous/reduced-intensity conditioning allogeneic stem-cell transplantation versus autologous transplantation in myeloma: long-term follow-up. J Clin Oncol 2011; 29: 3016–3022.

    Article  PubMed  Google Scholar 

  18. Cochran WG . The combination of estimates from different experiments. Biometrics 1954; 10: 101–129.

    Google Scholar 

  19. Higgins JP, Thompson SG . Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539–1558.

    Article  PubMed  Google Scholar 

  20. Mantel N, Haenszel W . Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959; 22: 719–748.

    CAS  PubMed  Google Scholar 

  21. DerSimonian R, Laird N . Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177–188.

    Article  CAS  PubMed  Google Scholar 

  22. Sterne JAC, Egger M, Moher D . Chapter 10: Addressing reporting biases. In: Higgins JP, Green S (eds) Cochrane Handbook for Systematic Reviews of Interventions. John Wiley & Sons: Chichester (UK), 2008.

    Google Scholar 

  23. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing, 2010.

  24. Schwarzer G . Meta-Analysis with R, R package version 1.6-0 ed, 2010.

  25. Moher D, Liberati A, Tetzlaff J, Altman DG . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 339: b2535.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Bruno B, Rotta M, Patriarca F, Mordini N, Allione B, Carnevale-Schianca F et al. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med 2007; 356: 1110–1120.

    Article  CAS  PubMed  Google Scholar 

  27. Giaccone L, Storer B, Patriarca F, Rotta M, Sorasio R, Allione B et al. Long-term follow-up of a comparison of nonmyeloablative allografting with autografting for newly diagnosed myeloma. Blood 2011; 117: 6721–6727.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Knop S, Liebisch P, Hebart H, Holler E, Engelhardt M, Bargou RC et al. Allogeneic stem cell transplant versus tandem high-dose melphalan for front-line treatment of deletion 13q14 myeloma—an interim analysis of the German DSMM V Trial. ASH Annu Meet Abstr 2009; 114: 51.

    Google Scholar 

  29. Krishnan A, Pasquini MC, Logan B, Stadtmauer EA, Vesole DH, Alyea E et al. Autologous haemopoietic stem-cell transplantation followed by allogeneic or autologous haemopoietic stem-cell transplantation in patients with multiple myeloma (BMT CTN 0102): a phase 3 biological assignment trial. Lancet Oncol 2011; 12: 1195–1203.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Rosinol L, Perez-Simon JA, Sureda A, de la Rubia J, de Arriba F, Lahuerta JJ et al. A prospective PETHEMA study of tandem autologous transplantation versus autograft followed by reduced-intensity conditioning allogeneic transplantation in newly diagnosed multiple myeloma. Blood 2008; 112: 3591–3593.

    Article  CAS  PubMed  Google Scholar 

  31. Moreau P, Garban F, Attal M, Michallet M, Marit G, Hulin C et al. Long-term follow-up results of IFM99-03 and IFM99-04 trials comparing nonmyeloablative allotransplantation with autologous transplantation in high-risk de novo multiple myeloma. Blood 2008; 112: 3914–3915.

    Article  CAS  PubMed  Google Scholar 

  32. Moreau P, Hullin C, Garban F, Yakoub-Agha I, Benboubker L, Attal M et al. Tandem autologous stem cell transplantation in high-risk de novo multiple myeloma: final results of the prospective and randomized IFM 99-04 protocol. Blood 2006; 107: 397–403.

    Article  CAS  PubMed  Google Scholar 

  33. Garban F, Attal M, Michallet M, Hulin C, Bourhis JH, Yakoub-Agha I et al. Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft (IFM99-03 trial) with tandem autologous stem cell transplantation (IFM99-04 trial) in high-risk de novo multiple myeloma. Blood 2006; 107: 3474–3480.

    Article  CAS  PubMed  Google Scholar 

  34. Harousseau JL, Attal M, Avet-Loiseau H . The role of complete response in multiple myeloma. Blood 2009; 114: 3139–3146.

    Article  CAS  PubMed  Google Scholar 

  35. Lokhorst HM, van der Holt B, Cornelissen JJ, Kersten MJ, van Oers M, Raymakers R et al. Donor versus no donor comparison of newly diagnosed myeloma patients included in the HOVON 50 multiple myeloma study. Blood 2012; 119: 6219–6225.

    Article  CAS  PubMed  Google Scholar 

  36. Gertz MA, Lacy MQ, Dispenzieri A, Greipp PR, Litzow MR, Henderson KJ et al. Clinical implications of t(11;14)(q13;q32), t(4;14)(p16.3;q32), and -17p13 in myeloma patients treated with high-dose therapy. Blood 2005; 106: 2837–2840.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Gertz MA, Kumar S, Lacy MQ, Dispenzieri A, Dingli D, Hayman SR et al. Stem cell transplantation in multiple myeloma: impact of response failure with thalidomide or lenalidomide induction. Blood 2010; 115: 2348–2353; quiz 2560.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The research presented in this article was supported in part by the Biostatistics Shared Resource as part of the Hollings Cancer Center at the Medical University of South Carolina which is funded by a Cancer Center Support Grant P30 CA138313. This study was presented at the 38th European Group or EBMT annual meeting in Geneva, Switzerland in 03 April 2012.

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Biostatistics and Epidemiology, Medical University of South Carolina, Charleston, SC, USA

    K E Armeson & E G Hill

  2. Department of Medicine, Division of Hematology and Medical Oncology, Medical University of South Carolina, Charleston, SC, USA

    L J Costa

Authors
  1. K E Armeson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E G Hill
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L J Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L J Costa.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on Bone Marrow Transplantation website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Armeson, K., Hill, E. & Costa, L. Tandem autologous vs autologous plus reduced intensity allogeneic transplantation in the upfront management of multiple myeloma: meta-analysis of trials with biological assignment. Bone Marrow Transplant 48, 562–567 (2013). https://doi.org/10.1038/bmt.2012.173

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2012.173

Keywords

This article is cited by

Search

Advanced search

Quick links