Abstract
We describe the use and outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for multiple myeloma (MM) in Europe between January 1990 and December 2012. We identified 7333 patients, median age at allo-HSCT was 51 years (range: 18–78), of whom 4539 (62%) were males. We distinguished three groups: (1) allo-HSCT upfront (n=1924), (2) tandem auto-allo-HSCT (n=2004) and (3) allo-HSCT as a second line treatment and beyond (n=3405). Overall, there is a steady increase in numbers of allo-HSCT over the years. Upfront allo-HSCT use increased up to year 2000, followed by a decrease thereafter and represented 12% of allo-HSCTs performed in 2012. Tandem auto-allo-HSCT peaked around year 2004 and contributed to 19% of allo-HSCTs in 2012. Allo-HSCT as salvage after one or two or three autografts was steadily increasing over the last years and represented 69% of allo-HSCTs in 2012. Remarkable heterogeneity in using allo-HSCT was observed among the different European countries. The 5-year survival probabilities from time of allo-HSCT for the three groups after year 2004 were 42%, 54% and 32%, respectively. These results show that the use of allo-HSCT is increasing in Europe, especially as second line treatment and beyond. There is an unmet need for well-designed prospective studies investigating allo-HSCT as salvage therapy for MM.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008; 111: 2516–2520.
Palumbo A, Anderson K . Multiple myeloma. N Engl J Med 2011; 364: 1046–1060.
Cavo M, Pantani L, Pezzi A, Petrucci MT, Patriarca F, Di Raimondo F et al. Bortezomib-thalidomide-dexamethasone (VTD) is superior to bortezomib-cyclophosphamide-dexamethasone (VCD) as induction therapy prior to autologous stem cell transplantation in multiple myeloma. Leukemia 2015; 29: 2429–2431.
Garderet L, Iacobelli S, Moreau P, Dib M, Lafon I, Niederwieser D et al. Superiority of the triple combination of bortezomib-thalidomide-dexamethasone over the dual combination of thalidomide-dexamethasone in patients with multiple myeloma progressing or relapsing after autologous transplantation: the MMVAR/IFM 2005-04 Randomized Phase III Trial from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 2012; 30: 2475–2482.
Harousseau JL, Attal M, Avet-Loiseau H, Marit G, Caillot D, Mohty M et al. Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial. J Clin Oncol 2010; 28: 4621–4629.
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: 1782–1791.
Mellqvist UH, Gimsing P, Hjertner O, Lenhoff S, Laane E, Remes K et al. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial. Blood 2013; 121: 4647–4654.
Roussel M, Lauwers-Cances V, Robillard N, Hulin C, Leleu X, Benboubker L et al. Front-line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myelome. J Clin Oncol 2014; 32: 2712–2717.
Blade J, Rosinol L, Cibeira MT, Rovira M, Carreras E . Hematopoietic stem cell transplantation for multiple myeloma beyond 2010. Blood 2010; 115: 3655–3663.
Engelhardt M, Udi J, Kleber M, Spencer A, Rocci A, Knop S et al. European Myeloma Network: the 3rd Trialist Forum Consensus Statement from the European experts meeting on multiple myeloma. Leuk Lymphoma 2010; 51: 2006–2011.
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.
Giralt S, Garderet L, Durie B, Cook G, Gahrton G, Bruno B et al. American Society of Blood and Marrow Transplantation, European Society of Blood and Marrow Transplantation, Blood and Marrow Transplant Clinical Trials Network, and International Myeloma Working Group Consensus Conference on salvage hematopoietic cell transplantation in patients with relapsed multiple myeloma. Biol Blood Marrow Transplant 2015; 21: 2039–2051.
Shah N, Callander N, Ganguly S, Gul Z, Hamadani M, Costa L et al. Hematopoietic stem cell transplantation for multiple myeloma: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2015; 21: 1155–1166.
Giralt S, Koehne G . Allogeneic hematopoietic stem cell transplantation for multiple myeloma: what place, if any? Curr Hematol Malign Rep 2013; 8: 284–290.
Lokhorst H, Einsele H, Vesole D, Bruno B, San Miguel J, Perez-Simon JA et al. International Myeloma Working Group consensus statement regarding the current status of allogeneic stem-cell transplantation for multiple myeloma. J Clin Oncol 2010; 28: 4521–4530.
Crawley C, Iacobelli S, Bjorkstrand B, Apperley JF, Niederwieser D, Gahrton G . Reduced-intensity conditioning for myeloma: lower nonrelapse mortality but higher relapse rates compared with myeloablative conditioning. Blood 2007; 109: 3588–3594.
Iacobelli S, de Wreede LC, Schonland S, Bjorkstrand B, Hegenbart U, Gruber A et al. Impact of CR before and after allogeneic and autologous transplantation in multiple myeloma: results from the EBMT NMAM2000 prospective trial. Bone Marrow Transplant 2015; 50: 505–510.
Duarte RF, Greinix H, Rabin B, Mitchell SA, Basak G, Wolff D et al. Uptake and use of recommendations for the diagnosis, severity scoring and management of chronic GVHD: an international survey of the EBMT-NCI Chronic GVHD Task Force. Bone Marrow Transplant 2014; 49: 49–54.
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.
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.
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: 5055–5063.
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.
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.
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.
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.
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.
Knop S, Liebisch P, Hebart H, Holler E, Engelhardt M, Bargou R . 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. Blood 2009; 115: 51.
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: 1195–1203.
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.
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.
Knop S, Liebisch P, Hebart H, Holler E, Engelhardt M, Bargou R . Autologous followed by allogeneic versus tandem-autologous stem cell transplant in newly diagnosed FISH-del13q myeloma. Blood 2014; 124: 43.
Blade J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G 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. European Group for Blood and Marrow Transplant. Br J Haematol 1998; 102: 1115–1123.
Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K et al. International uniform response criteria for multiple myeloma. Leukemia 2006; 20: 1467–1473.
Gahrton G, Krishnan A . Allogeneic transplantation in multiple myeloma. Exp Rev Hematol 2014; 7: 79–90.
Festuccia M, Martino M, Ferrando F, Messina G, Moscato T, Fedele R et al. Allogeneic stem cell transplantation in multiple myeloma: immunotherapy and new drugs. Exp Opin Biol Ther 2015; 15: 857–872.
Michallet M, Sobh M, El-Cheikh J, Morisset S, Sirvent A, Reman O et al. Evolving strategies with immunomodulating drugs and tandem autologous/allogeneic hematopoietic stem cell transplantation in first line high risk multiple myeloma patients. Exp Hematol 2013; 41: 1008–1015.
McCarthy PL, Einsele H, Attal M, Giralt S . The emerging role of consolidation and maintenance therapy for transplant-eligible multiple myeloma patients. Exp Rev Hematol 2014; 7: 55–66.
Caballero-Velazquez T, Lopez-Corral L, Encinas C, Castilla-Llorente C, Martino R, Rosinol L et al. Phase II clinical trial for the evaluation of bortezomib within the reduced intensity conditioning regimen (RIC) and post-allogeneic transplantation for high-risk myeloma patients. Br J Haematol 2013; 162: 474–482.
Kroger N, Zabelina T, Klyuchnikov E, Kropff M, Pfluger KH, Burchert A et al. Toxicity-reduced, myeloablative allograft followed by lenalidomide maintenance as salvage therapy for refractory/relapsed myeloma patients. Bone Marrow Transplant 2013; 48: 403–407.
Alsina M, Becker PS, Zhong X, Adams A, Hari P, Rowley S et al. Lenalidomide maintenance for high-risk multiple myeloma after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2014; 20: 1183–1189.
Corradini P, Voena C, Tarella C, Astolfi M, Ladetto M, Palumbo A et al. Molecular and clinical remissions in multiple myeloma: role of autologous and allogeneic transplantation of hematopoietic cells. J Clin Oncol 1999; 17: 208–215.
Martinelli G, Terragna C, Zamagni E, Ronconi S, Tosi P, Lemoli RM et al. Molecular remission after allogeneic or autologous transplantation of hematopoietic stem cells for multiple myeloma. J Clin Oncol 2000; 18: 2273–2281.
Ladetto M, Ferrero S, Drandi D, Festuccia M, Patriarca F, Mordini N et al. Prospective molecular monitoring of minimal residual disease after non-myeloablative allografting in newly diagnosed multiple myeloma. Leukemia 2015; 30: 1211–1214.
Corradini P, Cavo M, Lokhorst H, Martinelli G, Terragna C, Majolino I et al. Molecular remission after myeloablative allogeneic stem cell transplantation predicts a better relapse-free survival in patients with multiple myeloma. Blood 2003; 102: 1927–1929.
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.
Munshi NC, Anderson KC, Bergsagel PL, Shaughnessy J, Palumbo A, Durie B et al. Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2. Blood 2011; 117: 4696–4700.
Kroger N, Shimoni A, Schilling G, Schwerdtfeger R, Bornhauser M, Nagler A et al. Unrelated stem cell transplantation after reduced intensity conditioning for patients with multiple myeloma relapsing after autologous transplantation. Br J Haematol 2010; 148: 323–331.
Patriarca F, Einsele H, Spina F, Bruno B, Isola M, Nozzoli C et al. Allogeneic stem cell transplantation in multiple myeloma relapsed after autograft: a multicenter retrospective study based on donor availability. Biol Blood Marrow Transplant 2012; 18: 617–626.
Freytes CO, Vesole DH, LeRademacher J, Zhong X, Gale RP, Kyle RA et al. Second transplants for multiple myeloma relapsing after a previous autotransplant-reduced-intensity allogeneic vs autologous transplantation. Bone Marrow Transplant 2014; 49: 416–421.
San-Miguel JF, Hungria VT, Yoon SS, Beksac M, Dimopoulos MA, Elghandour A et al. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. Lancet Oncol 2014; 15: 1195–1206.
Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Spicka I, Oriol A et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med 2015; 372: 142–152.
Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, Spicka I et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med 2015; 373: 621–631.
Moreau PTMT, Norbert Grzasko N et al. Oral ixazomib, lenalidomide and dexamethasone for relapsed multiple myeloma. N Engl J Med 2016; 374: 1621–1634.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Sobh, M., Michallet, M., Gahrton, G. et al. Allogeneic hematopoietic cell transplantation for multiple myeloma in Europe: trends and outcomes over 25 years. A study by the EBMT Chronic Malignancies Working Party. Leukemia 30, 2047–2054 (2016). https://doi.org/10.1038/leu.2016.101
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/leu.2016.101
This article is cited by
-
Long-term outcomes of allogeneic stem cell transplant in multiple myeloma
Blood Cancer Journal (2023)
-
Maintenance therapy after allogeneic hematopoietic stem cell transplantation for patients with multiple myeloma
International Journal of Hematology (2023)
-
Long-term outcome after allogeneic stem cell transplantation in multiple myeloma
Annals of Hematology (2021)
-
Allogeneic Stem Cell Transplantation in Patients with High-Risk Multiple Myeloma: Utopia or Continuous Challenge in Aiming for Cure?
Current Treatment Options in Oncology (2021)
-
Second allogeneic stem cell transplantation for relapse after allografting in multiple myeloma using CD 34+ selected donor cells without immunosuppression
Bone Marrow Transplantation (2020)