Abstract
Multiple myeloma remains incurable despite the use of high-dose therapy and autologous stem cell transplantation and the introduction of novel agents with high response rates. The use of an uncontaminated stem cell graft and the presence of a graft-versus-myeloma effect led to the use of allogeneic stem cell transplantation in myeloma, and it has been part of the therapeutic armamentarium for more than a decade. Early results were discouraging due to high transplantation-related mortality and high rates of graft-versus-host disease. More recently, better supportive care, increasing experience with this modality and its complications, use of reduced-intensity conditioning regimens, and its use earlier in the course of disease have led to improved outcomes. Patients with high-risk genetic and biochemical features do poorly with conventional therapies, and allogeneic transplantation offers the potential for long-term disease control.
Similar content being viewed by others
References and Recommended Reading
Jemal A, Siegel R, Ward E, et al.: Cancer statistics, 2007. CA Cancer J Clin 2007, 57:43–66.
Myeloma Trialists’ Collaborative Group: Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. J Clin Oncol 1998, 16:3832–3842.
McElwain TJ, Powles RL: High-dose intravenous melphalan for plasma-cell leukaemia and myeloma. Lancet 1983, 8:822–824.
Barlogie B, Alexanian R, Dicke KA, et al.: High-dose chemoradiotherapy and autologous bone marrow transplantation for resistant multiple myeloma. Blood 1987, 70:869–872.
Attal M, Harousseau JL, Stoppa AM, 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.
Child JA, Morgan GJ, Davies FE, et al.: High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003, 348:1875–1883.
Attal M, Harousseau JL, Facon T, et al.: Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 2003, 349:2495–2502.
Kumar S, Rajkumar SV: Thalidomide and lenalidomide in the treatment of multiple myeloma. Eur J Cancer 2006, 42:1612–1622.
Rajkumar SV, Blood E, Vesole D, et al.: 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.
Rajkumar SV, Hayman SR, Lacy MQ, et al.: Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 2005, 106:4050–4053.
Singhal S, Mehta J, Desikan R, et al.: Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999, 341:1565–1571.
Richardson PG, Sonneveld P, Schuster MW, et al.: Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 2005, 352:2487–2498.
Kumar SK, Rajkumar SV, Dispenzieri A, et al.: Improved survival in multiple myeloma and the impact of novel therapies. Blood 2007 [Epub ahead of print].
Bergsagel PL, Kuehl WM: Molecular pathogenesis and a consequent classification of multiple myeloma. J Clin Oncol 2005, 23:6333–6338.
Dispenzieri A, Rajkumar SV, Gertz MA, et al.: Treatment of newly diagnosed multiple myeloma based on Mayo Stratification of Myeloma and Risk-adapted Therapy (mSMART): consensus statement. Mayo Clin Proc 2007, 82:323–341.
Tricot G, Vesole DH, Jagannath S, et al.: Graft-versus-myeloma effect: proof of principle. Blood 1996, 87:1196–1198.
Alyea E, Weller E, Schlossman R, et al.: Outcome after autologous and allogeneic stem cell transplantation for patients with multiple myeloma: impact of graft-versus-myeloma effect. Bone Marrow Transplant 2003, 32:1145–1151.
Huff CA, Fuchs EJ, Noga SJ, et al.: Long-term follow-up of T cell-depleted allogeneic bone marrow transplantation in refractory multiple myeloma: importance of allogeneic T cells. Biol Blood Marrow Transplant 2003, 9:312–319.
Lokhorst HM, Schattenberg A, Cornelissen JJ, et al.: Donor leukocyte infusions are effective in relapsed multiple myeloma after allogeneic bone marrow transplantation. Blood 1997, 90:4206–4211.
Martinelli G, Terragna C, Zamagni E, et al.: Molecular remission after allogeneic or autologous transplantation of hematopoietic stem cells for multiple myeloma. J Clin Oncol 2000, 18:2273–2281.
Alyea E, Weller E, Schlossman R, et al.: T-cell—depleted allogeneic bone marrow transplantation followed by donor lymphocyte infusion in patients with multiple myeloma: induction of graft-versus-myeloma effect. Blood 2001, 98:934–939.
Crawley C, Lalancette M, Szydlo R, et al.: Outcomes for reduced-intensity allogeneic transplantation for multiple myeloma: an analysis of prognostic factors from the Chronic Leukaemia Working Party of the EBMT. Blood 2005, 105:4532–4539.
Badros A, Barlogie B, Morris C, et al.: High response rate in refractory and poor-risk multiple myeloma after allotransplantation using a nonmyeloablative conditioning regimen and donor lymphocyte infusions. Blood 2001, 97:2574–2579.
Peggs KS, Mackinnon S, Williams CD, et al.: Reduced-intensity transplantation with in vivo T-cell depletion and adjuvant dose-escalating donor lymphocyte infusions for chemotherapy-sensitive myeloma: limited efficacy of graft-versus-tumor activity. Biol Blood Marrow Transplant 2003, 9:257–265.
Lokhorst HM, Wu K, Verdonck LF, 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.
Bensinger WI, Buckner CD, Anasetti C, et al.: Allogeneic marrow transplantation for multiple myeloma: an analysis of risk factors on outcome. Blood 1996, 88:2787–2793.
Hunter HM, Peggs K, Powles R, et al.: Analysis of outcome following allogeneic haemopoietic stem cell transplantation for myeloma using myeloablative conditioning—evidence for a superior outcome using melphalan combined with total body irradiation. Br J Haematol 2005, 128:496–502.
Lokhorst HM, Segeren CM, Verdonck LF, et al.: Partially T-cell-depleted allogeneic stem-cell transplantation for first-line treatment of multiple myeloma: a prospective evaluation of patients treated in the phase III study HOVON 24 MM. J Clin Oncol 2003, 21:1728–1733.
Ballen KK, King R, Carston M, et al.: Outcome of unrelated transplants in patients with multiple myeloma. Bone Marrow Transplant 2005, 35:675–681.
Bjorkstrand BB, Ljungman P, Svensson H, et al.: Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma: a retrospective case-matched study from the European Group for Blood and Marrow Transplantation. Blood 1996, 88:4711–4718.
Gahrton G, Svensson H, Cavo M, 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.
Giralt S, Aleman A, Anagnostopoulos A, et al.: Fludarabine/melphalan conditioning for allogeneic transplantation in patients with multiple myeloma. Bone Marrow Transplant 2002, 30:367–373.
Maloney DG, Molina AJ, Sahebi F, et al.: Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma. Blood 2003, 102:3447–3454.
Kroger N, Schwerdtfeger R, Kiehl M, 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.
Kroger N, Sayer HG, Schwerdtfeger R, 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, 100:3919–3924.
Crawley C, Iacobelli S, Bjorkstrand B, et al.: Reduced-intensity conditioning for myeloma: lower nonrelapse mortality but higher relapse rates compared with myeloablative conditioning. Blood 2007, 109:3588–3594.
Georges GE, Maris MB, Maloney DG, et al.: Nonmyeloablative unrelated donor hematopoietic cell transplantation to treat patients with poor-risk, relapsed, or refractory multiple myeloma. Biol Blood Marrow Transplant 2007, 13:423–432.
Bruno B, Sorasio R, Patriarca F, et al.: Unrelated donor haematopoietic cell transplantation after non-myeloablative conditioning for patients with high-risk multiple myeloma. Eur J Haematol 2007, 78:330–337.
Garban F, Attal M, Michallet M, 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.
Bruno B, Rotta M, Patriarca F, et al.: A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med 2007, 356:1110–1120.
Salama M, Nevill T, Marcellus D, et al.: Donor leukocyte infusions for multiple myeloma. Bone Marrow Transplant 2000, 26:1179–1184.
Lokhorst HM, Schattenberg A, Cornelissen JJ, 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.
Levenga H, Levison-Keating S, Schattenberg AV, et al.: Multiple myeloma patients receiving pre-emptive donor lymphocyte infusion after partial T-cell-depleted allogeneic stem cell transplantation show a long progression-free survival. Bone Marrow Transplant 2007, 40:355–359.
Peggs KS, Thomson K, Hart DP, et al.: Dose-escalated donor lymphocyte infusions following reduced intensity transplantation: toxicity, chimerism, and disease responses. Blood 2004, 103:1548–1556.
Arora M, McGlave PB, Burns LJ, et al.: Results of autologous and allogeneic hematopoietic cell transplant therapy for multiple myeloma. Bone Marrow Transplant 2005, 35:1133–1140.
Lokhorst HM, Sonneveld P, Cornelissen JJ, et al.: Induction therapy with vincristine, adriamycin, dexamethasone (VAD) and intermediate-dose melphalan (IDM) followed by autologous or allogeneic stem cell transplantation in newly diagnosed multiple myeloma. Bone Marrow Transplant 1999, 23:317–322.
Varterasian M, Janakiraman N, Karanes C, et al.: Transplantation in patients with multiple myeloma: a multicenter comparative analysis of peripheral blood stem cell and allogeneic transplant. Am J Clin Oncol 1997, 20:462–466.
Couban S, Stewart AK, Loach D, et al.: Autologous and allogeneic transplantation for multiple myeloma at a single centre. Bone Marrow Transplant 1997, 19:783–789.
Reynolds C, Ratanatharathorn V, Adams P, et al.: Allogeneic stem cell transplantation reduces disease progression compared to autologous transplantation in patients with multiple myeloma. Bone Marrow Transplant 2001, 27:801–807.
Kuruvilla J, Shepherd JD, Sutherland HJ, et al.: Long-term outcome of myeloablative allogeneic stem cell transplantation for multiple myeloma. Biol Blood Marrow Transplant 2007, 13:925–931.
Perez-Simon JA, Martino R, Alegre A, et al.: Chronic but not acute graft-versus-host disease improves outcome in multiple myeloma patients after non-myeloablative allogeneic transplantation. Br J Haematol 2003, 121:104–108.
Gerull S, Goerner M, Benner A, et al.: Long-term outcome of nonmyeloablative allogeneic transplantation in patients with high-risk multiple myeloma. Bone Marrow Transplant 2005, 36:963–969.
Majolino I, Davoli M, Carnevalli E, et al.: Reduced intensity conditioning with thiotepa, fludarabine, and melphalan is effective in advanced multiple myeloma. Leuk Lymphoma 2007, 48:759–766.
Shimazaki C, Fujii H, Yoshida T, et al.: Reduced-intensity conditioning allogeneic stem cell transplantation for multiple myeloma: results from the Japan Myeloma Study Group. Int J Hematol 2005, 81:342–348.
Mohty M, Boiron JM, Damaj G, et al.: Graft-versus-myeloma effect following antithymocyte globulin-based reduced intensity conditioning allogeneic stem cell transplantation. Bone Marrow Transplant 2004, 34:77–84.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kumar, S. Role of allogeneic stem cell transplantation in multiple myeloma. Curr Hematol Malig Rep 3, 99–106 (2008). https://doi.org/10.1007/s11899-008-0015-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11899-008-0015-9