Skip to main content

Thank you for visiting 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.

Multiple myeloma gammopathies

Allogeneic transplantation in multiple myeloma: long-term follow-up and cytogenetic subgroup analysis



This phase 3 trial compared tandem autologous stem cell transplantation (autoSCT) versus autoSCT followed by reduced-intensity conditioning allogeneic stem cell transplantation (auto/alloSCT) in patients with newly diagnosed multiple myeloma (MM) with deletion of (del) chromosome 13q (del13q). The availability/absence of a human leukocyte antigen-matched-related or matched-unrelated donor (MUD) determined the nature of the second SCT. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population (n= 199). Auto/alloSCT was performed in 126 patients; 74 received MUD allografts. After 91 months median follow-up, median PFS with auto/allo versus tandem autoSCT was 34.5 versus 21.8 months (P = 0.003; adjusted hazard ratio 0.55, 95% confidence interval 0.36–0.84). Median overall survival (OS) was 70.2 versus 71.8 months (P= 0.856). Two-year non-relapse mortality with auto/allo versus tandem autoSCT was 14.3% versus 4.1% (P= 0.008). In patients harboring both del13q and del17p, median PFS and OS were 37.5 and 61.5 months with auto/allo (n= 19) versus 6.1 and 23.4 months with tandem autoSCT (n = 6) (P= 0.0002 and 0.032). Our findings suggest that auto/alloSCT significantly extends PFS versus tandem autoSCT in del13q MM, and indicate some survival benefit for first-line alloSCT in high-risk MM.

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type



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

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. Rollig C, Knop S, Bornhauser M. Multiple myeloma. Lancet. 2015;385:2197–208.

    Article  Google Scholar 

  2. 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  Google Scholar 

  3. 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;349:2495–502.

    Article  CAS  Google Scholar 

  4. Bolli N, Avet-Loiseau H, Wedge DC, Van Loo P, Alexandrov LB, Martincorena I, et al. Heterogeneity of genomic evolution and mutational profiles in multiple myeloma. Nat Commun. 2014;5:2997.

    Article  Google Scholar 

  5. Melchor L, Brioli A, Wardell CP, Murison A, Potter NE, Kaiser MF, et al. Single-cell genetic analysis reveals the composition of initiating clones and phylogenetic patterns of branching and parallel evolution in myeloma. Leukemia. 2014;28:1705–15.

    Article  CAS  Google Scholar 

  6. 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;107:3474–80.

    Article  CAS  Google Scholar 

  7. 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;356:1110–20.

    Article  CAS  Google Scholar 

  8. 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;112:3591–3.

    Article  CAS  Google Scholar 

  9. 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;29:3016–22.

    Article  Google Scholar 

  10. 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;119:6219–25.

    Article  CAS  Google Scholar 

  11. Krishnan A, Pasquini MC, Logan B, Stadtmauer EA, Vesole DH, Alyea E 3rd, 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;12:1195–203.

    Article  Google Scholar 

  12. Fonseca R, Bergsagel PL, Drach J, Shaughnessy J, Gutierrez N, Stewart AK, et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009;23:2210–21.

    Article  CAS  Google Scholar 

  13. Konigsberg R, Zojer N, Ackermann J, Kromer E, Kittler H, Fritz E, et al. Predictive role of interphase cytogenetics for survival of patients with multiple myeloma. J Clin Oncol. 2000;18:804–12.

    Article  CAS  Google Scholar 

  14. Facon T, Avet-Loiseau H, Guillerm G, Moreau P, Genevieve F, Zandecki M, et al. Chromosome 13 abnormalities identified by FISH analysis and serum beta2-microglobulin produce a powerful myeloma staging system for patients receiving high-dose therapy. Blood. 2001;97:1566–71.

    Article  CAS  Google Scholar 

  15. Avet-Loiseau H, Attal M, Campion L, Caillot D, Hulin C, Marit G, et al. Long-term analysis of the IFM 99 trials for myeloma: cytogenetic abnormalities [t(4;14), del(17p), 1q gains] play a major role in defining long-term survival. J Clin Oncol. 2012;30:1949–52.

    Article  Google Scholar 

  16. McQuaker I, Haynes A, Stainer C, Byrne J, Russell N. Mobilisation of peripheral blood stem cells with IVE and G-CSF improves CD34+ cell yields and engraftment in patients with non-Hodgkin’s lymphomas and Hodgkin’s disease. Bone Marrow Transplant. 1999;24:715–22.

    Article  CAS  Google Scholar 

  17. Ross FM, Avet-Loiseau H, Ameye G, Gutierrez NC, Liebisch P, O’Connor S, et al. Report from the European Myeloma Network on interphase FISH in multiple myeloma and related disorders. Haematologica. 2012;97:1272–7.

    Article  Google Scholar 

  18. Gahrton G, Iacobelli S, Bjorkstrand B, Hegenbart U, Gruber A, Greinix H, et al. Autologous/reduced-intensity allogeneic stem cell transplantation vs autologous transplantation in multiple myeloma: long-term results of the EBMT-NMAM2000 study. Blood. 2013;121:5055–63.

    Article  CAS  Google Scholar 

  19. Lokhorst HM, van der Holt B, Cornelissen JJ, Kersten MJ, van Oers M, Raymakers R, et al. Reduced relapse rate in upfront tandem autologous/reduced-intensity allogeneic transplantation in multiple myeloma only results in borderline non-significant prolongation of progression-free but not overall survival. Haematologica. 2015;100:e508–510.

    Article  CAS  Google Scholar 

  20. Kroger N, Sayer HG, Schwerdtfeger R, Kiehl M, Nagler A, Renges H, et al. Unrelated stem cell transplantation in multiple myeloma after a reduced-intensity conditioning with pretransplantation antithymocyte globulin is highly effective with low transplantation-related mortality. Blood. 2002;100:3919–24.

    Article  CAS  Google Scholar 

  21. Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, et al. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012;30:2946–55.

    Article  CAS  Google Scholar 

  22. Kroger N, Badbaran A, Zabelina T, Ayuk F, Wolschke C, Alchalby H, et al. Impact of high-risk cytogenetics and achievement of molecular remission on long-term freedom from disease after autologous-allogeneic tandem transplantation in patients with multiple myeloma. Biol Blood Marrow Transplant. 2013;19:398–404.

    Article  Google Scholar 

  23. Avet-Loiseau H, Leleu X, Roussel M, Moreau P, Guerin-Charbonnel C, Caillot D, et al. Bortezomib plus dexamethasone induction improves outcome of patients with t(4;14) myeloma but not outcome of patients with del(17p). J Clin Oncol. 2010;28:4630–4.

    Article  CAS  Google Scholar 

  24. Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366:1782–91.

    Article  CAS  Google Scholar 

  25. Avet-Loiseau H, Fonseca R, Siegel D, Dimopoulos MA, Spicka I, Masszi T, et al. Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma. Blood. 2016;128:1174–80.

    Article  CAS  Google Scholar 

  26. Koreth J, Stevenson KE, Kim HT, McDonough SM, Bindra B, Armand P, et al. Bortezomib-based graft-versus-host disease prophylaxis in HLA-mismatched unrelated donor transplantation. J Clin Oncol. 2012;30:3202–8.

    Article  CAS  Google Scholar 

  27. Passera R, Pollichieni S, Brunello L, Patriarca F, Bonifazi F, Montefusco V, et al. Allogeneic hematopoietic cell transplantation from unrelated donors in multiple myeloma: study from the Italian Bone Marrow Donor Registry. Biol Blood Marrow Transplant. 2013;19:940–8.

    Article  Google Scholar 

  28. Gerull S, Goerner M, Benner A, Hegenbart U, Klein U, Schaefer H, et al. Long-term outcome of nonmyeloablative allogeneic transplantation in patients with high-risk multiple myeloma. Bone Marrow Transplant. 2005;36:963–9.

    Article  CAS  Google Scholar 

Download references


We would like to thank the patients who consented to participate, their families and caregivers, and the study nurses in the DSMM centers. We are indebted to Martina Haase, Lisa Hubert, Annette Nobis, and Verena Pscheidl for their help in putting long-term follow-up data together, and to Sandralee Lewis, PhD, working on behalf of the Investigator Initiated Research Writing Group (an initiative from Ashfield Healthcare Communications, part of UDG Healthcare plc), for medical writing support (funded by Würzburg University Medical Center). The trial was sponsored by Würzburg University, Würzburg, Germany.

Investigators of the German Myeloma Study Group DSMM (Deutsche Studiengruppe Multiples Myelom) are as follows:

O. Sezer30, B. Dörken30, C. Gerecke31, S. Fuhrmann31, W. D. Ludwig31, B. Hertenstein32, M. Bormann32, R. Meyer33, R. Naumann34, U. Platzbecker34, Ch. Röllig34, W. Rösler35, I. von Metzler36, H. Martin36, M. Engelhardt37, J. Finke37, L. Trümper38, W. Jung38, Ch. A. Schmidt39, G. Dölken39, H. H. Wolf40, L. Müller40, K. Ligeti40, N. Kröger41, G. Schilling41, H. Dürk42, D. Peest43, A. Ganser43, M. Pfreundschuh44, H. Sayer45, M. von Lilienfeld-Toal45, L. O. Mügge45, M. Bentz46, M. Gramatzki47, M. Brüggemann47, T. Fischer48, D. Wolleschak10, G. Hess49, M. Kropff50, J. Reusch50, C. Straka51, H. Ostermann52, D. Franke52, C. Peschel53, T. Dechow53, F. Bassermann53, M. Hentrich54, H. Wandt55, K. Schäfer-Eckart55, B. Metzner56, G. Maschmeyer57, E. Holler58, C. Hart58, A. Reichle58, M. Freund59, S. Böttcher59, C. Kahl59, H. G. Mergenthaler60, W. Aulitzky61, M. Kaufmann61, J. Greiner62, E. Heidemann62, L. Kanz63, H. Hebart63, P. Liebisch3, D. Bunjes3, C. Langer3, N. Frickhofen64, H. Einsele1, S. Knop1, S. Mielke1, R. C. Bargou1, M. Svaldi65

Author information

Authors and Affiliations




CM, CS, HH, and HE conceived and designed the work that led to the submission. SK, ME, PL, EH, BM, DP, MK, CAS, DB, TF, OS, MH, HO, FB, GH, BH, MF, MK, H-HW, WJ, NF, SM, RCB, GM, MS, CHL, MG, HH, LK, and HE acquired data and played an important role in interpreting the results. SK, ME, CM, and HE drafted the manuscript. PL, EH, BM, DP, MK, DB, CS, TF, OS, MH, HO, FB, GH, BH, MF, MK, CAS, H-HW, WJ, NF, SM, RCB, GM, MS, CHL, MG, HH, and LK revised the manuscript. CM conducted all the reported statistical analyses. All the authors approved the final version of the manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Hermann Einsele.

Ethics declarations

Conflict of interest

MH reports personal fees from Amgen, Celgene, Janssen, Bristol-Myers Squibb, and Takeda. GH reports personal fees from Janssen, Roche, AbbVie, Gilead, Novartis, MorphoSys, and Celgene; and grants from Roche, Pfizer, and Celgene. SM reports non-financial support from EBMT/EHA, IACH, Celgene, Miltenyi, KIADIS, Bellicum, DGHO, Jazz Pharma, and ISCT; and personal fees from Celgene, Miltenyi, KIADIS, Bellicum, and Jazz Pharma. GM reports personal fees from Gilead, Pfizer, Boehringer Ingelheim, Bristol-Myers Squibb, and Merck-Serono; and non-financial support from Janssen-Cilag. LK reports honoraria for presentation at “MedIpdate” (OnkoUpdate, IntemistenUpdate, PraxisUpdate) and at “Medizin Aktuell”. Amgen and Celgene are sponsors of the “Biannual International Stem Cell Conference, Tübingen, Germany): Scientific chairman: LK. HE reports grants, personal fees, and other (advisory board) from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Novartis, and Takeda. The other authors declare that they have no conflict of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Investigators of the German Myeloma Study Group DSMM (Deutsche Studiengruppe Multiples Myelom) are listed at the end of the paper.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Knop, S., Engelhardt, M., Liebisch, P. et al. Allogeneic transplantation in multiple myeloma: long-term follow-up and cytogenetic subgroup analysis. Leukemia 33, 2710–2719 (2019).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links