Abstract
High-dose melphalan with autologous hematopoietic SCT (HSCT) improves response rates and survival in myeloma. This is despite the fact that unlike other hematologic malignancies treated with high-dose therapy and autotransplantation, autografted myeloma patients continue to relapse several years after transplantation and the procedure is not curative in the majority of patients. However, patients surviving for several years with essentially normal quality of life may be considered to be ‘operationally cured.’ Also, unlike with other hematologic malignancies relapsing after an autograft, recurrent disease can be treated with novel agents or repeat high-dose chemotherapy and autologous or allogeneic HSCT—and long-term survival is seen in a number of patients after relapse. Although tandem transplantation is clearly superior to a single autograft, it is unclear if this should be offered to all patients routinely or only to those not attaining CR after one transplant. It is also unclear if novel agents should be used before transplantation or reserved for relapse. Despite their excellent activity, there is no evidence that novel agents such as thalidomide, bortezomib and lenalidomide can replace high-dose chemotherapy and HSCT, and the best strategy is to use all options in all eligible patients at appropriate stages of the disease.
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
McElwain TJ, Powles RL . High-dose intravenous melphalan for plasma-cell leukaemia and myeloma. Lancet 1983; 2: 822–824.
Singhal S . High-dose therapy and autologous transplantation. In: Mehta J, Singhal S (eds). Myeloma, Martin Dunitz: London, 2002, pp 327–347.
Barlogie B, Hall R, Zander A, Dicke K, Alexanian R . High-dose melphalan with autologous bone marrow transplantation for multiple myeloma. Blood 1986; 67: 1298–1301.
Sirohi B, Powles R, Mehta J, Rudin C, Kulkarni S, Horton C et al. An elective single autograft with high-dose melphalan: single-center study of 451 patients. Bone Marrow Transplant 2005; 36: 19–24.
Mehta J, Singhal S . High-dose chemotherapy and autologous hematopoietic stem cell transplantation in myeloma patients under the age of 65 years. Bone Marrow Transplant 2007; 40: 1101–1114.
Powles R, Sirohi B, Treleaven J, Singhal S, Kulkarni S, Lal R et al. Continued first complete remission in multiple myeloma for over 10 years: a series of ‘operationally cured’ patients. Blood (ASH Annual Meeting Abstracts) 2000; 96: Abstract 2215.
Powles R, Singhal S, Sirohi B, Horton C, Treleaven J, Mehta J . ‘Discontinuous complete remission’: a new endpoint to evaluate the success of therapy in keeping myeloma patients disease-free for extended periods of time. Blood (ASH Annual Meeting Abstracts) 2001; 98: 166a.
Barlogie B, Tricot GJ, van Rhee F, Angtuaco E, Walker R, Epstein J et al. Long-term outcome results of the first tandem autotransplant trial for multiple myeloma. Br J Haematol 2006; 135: 158–164.
Siegel DS, Desikan KR, Mehta J, Singhal S, Fassas A, Munshi N et al. Age is not a prognostic variable with autotransplants multiple myeloma. Blood 1999; 93: 51–54.
Sirohi B, Powles R, Treleaven J, Mainwaring P, Kulkarni S, Pandha H et al. The role of autologous transplantation in patients with multiple myeloma aged 65 years and over. Bone Marrow Transplant 2000; 25: 533–539.
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 Français du Myelome. N Engl J Med 1996; 335: 91–97.
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.
Palumbo A, Bringhen S, Petrucci MT, Musto P, Rossini F, Nunzi M et al. Intermediate-dose melphalan improves survival of myeloma patients aged 50–70: results of a randomized controlled trial. Blood 2004; 104: 3052–3057.
Bladé J, Rosiñol L, Sureda A, Ribera JM, Díaz-Mediavilla J, García-Laraña 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.
Fermand JP, Katsahian S, Divine M, Leblond V, Dreyfus F, Macro M et al. High-dose therapy and autologous blood stem-cell transplantation compared with conventional treatment in myeloma patients aged 55–65 years: long-term results of a randomized control trial from the Group Myelome-Autogreffe. J Clin Oncol 2005; 23: 9227–9233.
Powles R, Raje N, Milan S, Millar B, Shepherd V, Mehta J 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.
Desikan KR, Tricot G, Dhodapkar M, Fassas A, Siegel D, Vesole DH 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.
Moreau P, Facon T, Attal M, Hulin C, Michallet M, Maloisel F 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 Myélome 9502 randomized trial. Blood 2002; 99: 731–735.
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.
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.
Singhal S . Treatment of multiple myeloma. BMJ 2003; 327: 575–576.
Barlogie B, Jagannath S, Desikan KR, Mattox S, Vesole D, Siegel D et al. Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood 1999; 93: 55–65.
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.
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.
Fermand JP . MAG studies (1985–2005). 10th International Myeloma Workshop, Sydney, April 2005 Accessed 2 December 2006. http://myeloma.org/pdfs/Sydney2005_Fermand_P8.pdf.
Goldschmidt H . Single vs double HDT in multiple myeloma: third analysis of the trial GMMG-HD2. 10th International Myeloma Workshop, Sydney, April 2005. Accessed 2 December 2006. http://myeloma.org/pdfs/Sydney2005_Goldschmidt_P8.pdf.
Segeren CM, Sonneveld P, van der Holt B, Vellenga E, Croockewit AJ, Verhoef GE et al. Overall and event-free survival are not improved by the use of myeloablative therapy following intensified chemotherapy in previously untreated patients with multiple myeloma: a prospective randomized phase 3 study. Blood 2003; 101: 2144–2151.
Sonneveld P, van der Holt B, Vellenga E, Croockewit S, Verhoef G, Segeren C et al. Intensive versus double intensive therapy in untreated multiple myeloma: final analysis of the HOVON 24 trial. Blood (ASH Annual Meeting Abstracts) 2005; 106: Abstract 2545.
Mehta J, Tricot G, Jagannath S, Ayers D, Singhal S, Siegel D et al. Salvage autologous or allogeneic transplantation for multiple myeloma refractory to or relapsing after a first-line autograft? Bone Marrow Transplant 1998; 21: 887–892.
Sirohi B, Powles R, Mehta J, Kulkarni S, Sankpal S, Treleaven J et al. Prognostic factors at the time of single autotransplantation in 451 myeloma patients treated with 200 mg/m2 melphalan: results equivalent to tadem autotransplantation. Blood (ASH Annual Meeting Abstracts) 2002; 100: Abstract 673.
Singhal S, Powles R, Sirohi B, Treleaven J, Kulkarni S, Mehta J . Response to induction chemotherapy is not essential to obtain survival benefit from high-dose melphalan and autotransplantation in myeloma. Bone Marrow Transplant 2002; 30: 673–679.
Powles R, Sirohi B, Kulkarni S, Treleaven J, Rudin C, Sankpal S et al. Collection of peripheral blood stem cells in newly diagnosed myeloma patients without any prior cytoreductive therapy: the first step towards an ‘operational cure’? Bone Marrow Transplant 2002; 30: 479–484.
Kumar S, Lacy MQ, Dispenzieri A, Rajkumar SV, Fonseca R, Geyer S et al. Single agent dexamethasone for pre-stem cell transplant induction therapy for multiple myeloma. Bone Marrow Transplant 2004; 34: 485–490.
Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR . Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol 2006; 24: 431–436.
Singhal S, Mehta J . Multiple myeloma. Clin J Am Soc Nephrol 2006; 1: 1322–1330.
Kumar S, Lacy MQ, Dispenzieri A, Hayman SR, Rajkumar SV, Zeldenrust S et al. Analysis of outcome after autologous stem transplantation in patients with newly diagnosed myeloma: comparison of different induction regimens. Blood (ASH Annual Meeting Abstracts) 2006; 108: Abstract 3079.
Barlogie B, Tricot G, Anaissie E, Shaughnessy J, Rasmussen E, van Rhee F et al. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med 2006; 354: 1021–1030.
Cunningham D, Powles R, Malpas J, Raje N, Milan S, Viner C et al. A randomized trial of maintenance interferon following high-dose chemotherapy in multiple myeloma: long-term follow-up results. Br J Haematol 1998; 102: 495–502.
Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999; 341: 1565–1571.
Attal M, Harousseau JL, Leyvraz S, Doyen C, Hulin C, Benboubker L et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood 2006; 108: 3289–3294.
Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Blade J et al. International staging system for multiple myeloma. J Clin Oncol 2005; 23: 3412–3420.
Tricot G, Sawyer JR, Jagannath S, Desikan KR, Siegel D, Naucke S et al. Unique role of cytogenetics in the prognosis of patients with myeloma receiving high-dose therapy and autotransplants. J Clin Oncol 1997; 15: 2659–2666.
Desikan R, Barlogie B, Sawyer J, Ayers D, Tricot G, Badros A et al. Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities. Blood 2000; 95: 4008–4010.
Crowley JJ, McCoy J, LeBlanc M, Barlogie B . Extreme regression: a statistical technique for finding good or poor prognostic groups, illustrated using myeloma patient data from intergroup trial S9321. Blood (ASH Annual Meeting Abstracts) 2004; 102: Abstract 5202.
Barlogie B, Desikan R, Eddlemon P, Spencer T, Zeldis J, Munshi N et al. Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients. Blood 2001; 98: 492–494.
Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 2003; 348: 2609–2617.
Singhal S, Mehta J . Lenalidomide in myeloma. Curr Treatment Options Oncol 2007; 8: 154–163.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mehta, J., Singhal, S. Current status of autologous hematopoietic stem cell transplantation in myeloma. Bone Marrow Transplant 42 (Suppl 1), S28–S34 (2008). https://doi.org/10.1038/bmt.2008.109
Published:
Issue Date:
DOI: https://doi.org/10.1038/bmt.2008.109
Keywords
This article is cited by
-
Cyclophosphamide vs salvage chemotherapy plus G-CSF as chemo-mobilization in Asian patients undergoing autologous hematopoietic stem cell transplant
Bone Marrow Transplantation (2017)
-
Clinical impact and resource utilization after stem cell mobilization failure in patients with multiple myeloma and lymphoma
Bone Marrow Transplantation (2010)
-
Peripheral blood stem cell collection in elderly patients
Annals of Hematology (2010)
-
A simplified method for stem cell autografting in multiple myeloma: a single institution experience
Bone Marrow Transplantation (2009)
-
International myeloma working group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100)
Leukemia (2009)