Skip to main content
Log in

Recent Developments in Hematopoietic Stem Cell Transplantation for Multiple Myeloma

  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Multiple myeloma (MM) is often successfully controlled with conventional chemotherapy; however, complete remissions are uncommon, and cure is rare. High-dose therapy followed by administration of autologous or allogeneic stem cells, used for the treatment of MM in the past 15 years, is promising as a means of increasing remission rates and improving survival. Autologous transplantation has not always demonstrated survival benefits in randomized studies because most of the patients receiving transplants have relapses, whereas patients given conventional therapy can receive salvage transplants when relapse occurs. Efforts to improve the results of autologous transplantation include targeted radiat0ion, tandem transplantation, and posttransplantation immunotherapy. Only allogeneic hematopoietic stem cell transplantation is potentially curative, owing to a graft-versus-myeloma effect. Although patients who receive either allogeneic or 0autologous stem cell transplants for MM have similar 3- to 5-year survival rates, only allograft recipients appear to enjoy long-term disease-free survival. High transplantation-related mortality associated with allogeneic stem cell transplantation is currently the major limitation to wider use of this potentially curative modality. Strategies designed to improve the therapeutic index of allografts include the use of nonablative conditioning regimens, peripheral blood cells rather than bone marrow, graft engineering, and targeted conditioning therapies, such as bone-seeking radioisotopes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Buckner CD, Fefer A, Bensinger WI, et al. Marrow transplantation for malignant plasma cell disorders: summary of the Seattle Experience.Eur J Haematol. 1989;43(suppl 51):186–190.

    Google Scholar 

  2. Gahrton G, Svensson H, Bjürkstrand B, et al. Syngeneic transplantation in multiple myeloma: a case-matched comparison with autologous and allogeneic transplantation.Bone Marrow Transplant. 1999;24:741–745.

    Article  PubMed  CAS  Google Scholar 

  3. Bensinger WI, Demirer T, Buckner CD, et al. Syngeneic marrow transplantation in patients with multiple myeloma.Bone Marrow Transplant. 1996;18:527–531.

    PubMed  CAS  Google Scholar 

  4. McElwain TJ, Powles RL. High-dose intravenous melphalan for plasma cell leukaemia and myeloma.Lancet. 1983;1:822–824.

    Article  Google Scholar 

  5. Tricot G, Vesole DH, Jagannath S, Hilton J, Munshi N, Barlogie B. Graft-versus-myeloma effect: proof of principle.Blood. 1996;87:1196–11988.

    Article  PubMed  CAS  Google Scholar 

  6. Verdonck LF, Lokhorst HM, Dekker AW, Nieuwenhuis HK, Petersen EJ. Graft-versus-myeloma effect in two cases.Lancet. 1996;347:800–801.

    Article  PubMed  CAS  Google Scholar 

  7. Aschan J, Lonnqvist B, Ringden O, Kumlien G, Gahrton G. Graftversusmyeloma effect [letter].Lancet. 1996;348:346.

    Article  PubMed  CAS  Google Scholar 

  8. Attal M, Harousseau J-L, Stoppa A-M, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma.N Engl J Med. 1996;335:91–97.

    Article  PubMed  CAS  Google Scholar 

  9. Attal M, Harousseau JL, Stoppa AM, et al. High dose therapy in multiple myeloma: an updated analysis of the IFM 90 protocol [abstract].Blood. 1998;92(suppl 1):418a. Abstract 1858.

    Google Scholar 

  10. Morgan GJ, Davies FE, Hawkins K, et al. The MRC myeloma VII trial of standard versus intensive treatment in patients <65 years of age with multiple myeloma [abstract].Blood. 2002;100:178a. Abstract 668.

    Article  CAS  Google Scholar 

  11. Macfarlane DJ, Durrant S, Bartlett ML, Allison R, Morton AJ. 153Sm EDTMP for bone marrow ablation prior to stem cell transplantation for haematological malignancies.Nucl Med Commun. 2002;23:1099–1106.

    Article  PubMed  CAS  Google Scholar 

  12. Rasmussen T, Bjorkstrand B, Andersen H, Gaarsdal E, Johnsen HE. Efficacy and safety of CD34-selected and CD19-depleted autografting in multiple myeloma patients: a pilot study.Exp Hematol. 2002;30:82–88.

    Article  PubMed  Google Scholar 

  13. Moreau P, Facon T, Attal M, 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.

    Article  PubMed  CAS  Google Scholar 

  14. Attal M, Harousseau J-L, Facon T, et al. Double autologous transplantation improves survival of multiple myeloma patients: final analysis of a prospective randomized study of the “Intergroupe Francophone du Myélome” (IFM 94) [abstract].Blood. 2002;100:5a. Abstract 7.

    Google Scholar 

  15. Cavo M, Tosi P, Zamagni E, et al. The “Bologna 96” clinical trial of single vs. double autotransplants for previously untreated multiple myeloma patients [abstract].Blood. 2002;100:179a. Abstract 669.

    Article  Google Scholar 

  16. Giralt S, Bensinger W, Goodman M, et al. Long-term follow-up of 83 patients with multiple myeloma (MM) treated on a phase I-II study of skeletal targeted radiotherapy (STR) using 166Ho- DOTMP plus melphalan with or without total body irradiation (TBI) and autologous hematopoietic stem cell transplant (AHSCT) [abstract]. Blood. 2002;179a. Abstract 670.

  17. Fermand J-P, Ravaud P, Chevret S, 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.

    Article  PubMed  CAS  Google Scholar 

  18. Massaia M, Borrione P, Battaglio S, et al. Idiotype vaccination in human myeloma: generation of tumor-specific immune responses after high-dose chemotherapy.Blood. 1999;94:673–683.

    Article  PubMed  CAS  Google Scholar 

  19. Lim SH, Bailey-Wood R. Idiotypic protein-pulsed dendritic cell vaccination in multiple myeloma.Int J Cancer. 1999;83:215–222.

    Article  PubMed  CAS  Google Scholar 

  20. Cull G, Durrant L, Stainer C, Haynes A, Russell N. Generation of anti-idiotype immune responses following vaccination with idiotype- protein pulsed dendritic cells in myeloma.Br J Haematol. 1999;107:648–655.

    Article  PubMed  CAS  Google Scholar 

  21. Titzer S, Christensen O, Manzke O, et al. Vaccination of multiple myeloma patients with idiotype-pulsed dendritic cells: immunological and clinical aspects.Br J Haematol. 2000;108:805–816.

    Article  PubMed  CAS  Google Scholar 

  22. Chiriva-Internati M, Wang Z, Salati E, Bumm K, Barlogie B, Lim SH. Sperm protein 17 (Sp17) is a suitable target for immunotherapy of multiple myeloma.Blood. 2002;100:961–965.

    Article  PubMed  CAS  Google Scholar 

  23. Gahrton G, Svensson H, Cavo M, et al. Progress in allogeneic bone marrow and peripheral blood stem cell transplantation for multiple myeloma: a comparison between transplants performed 1983- 93 and 1994-98 at European Group for Blood and Marrow Transplantation centres.Br J Haematol. 2001;113:209–216.

    Article  PubMed  CAS  Google Scholar 

  24. 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.

    Article  PubMed  CAS  Google Scholar 

  25. Roberts RT. Usefulness of immunofixation electrophoresis in the clinical laboratory.Clin Lab Med. 1986;6:601–605.

    Article  PubMed  CAS  Google Scholar 

  26. Bladé J, Samson D, Reece D, 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;102:1115–11233.

    Article  PubMed  Google Scholar 

  27. Ludwig H, Fruhwald F, Tscholakoff D, Rasoul S, Neuhold A, Fritz E. Magnetic resonance imaging of the spine in multiple myeloma.Lancet. 1987;2:364–366.

    Article  PubMed  CAS  Google Scholar 

  28. Laroche M, Assoun J, Sixou L, Attal M. Comparison of MRI and computed tomography in the various stages of plasma disorders: correlations with biological and histological findings. Myeloma- Midi-Pyrenees Group.Clin Exp Rheumatol. 1996;14:171–176.

    PubMed  CAS  Google Scholar 

  29. Billadeau D, Blackstadt M, Greipp P, et al. Analysis of B-lymphoid malignancies using allele-specific polymerase chain reaction: a technique for sequential quantitation of residual disease.Blood. 1991;78:3021–3029.

    Article  PubMed  CAS  Google Scholar 

  30. Bird JM, Russell NH, Samson D. Minimal residual disease after bone marrow transplantation for multiple myeloma: evidence for cure in long-term survivors.Bone Marrow Transplant. 1993;12:651–6544.

    PubMed  CAS  Google Scholar 

  31. 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.

    Article  PubMed  CAS  Google Scholar 

  32. Cavo M, Terragna C, Martinelli G, et al. Molecular monitoring of minimal residual disease in patients in long-term complete remission after allogeneic stem cell transplantation for multiple myeloma.Blood. 2000;96:355–357.

    Article  PubMed  CAS  Google Scholar 

  33. Corradini P, Voena C, Tarella C, et al. Molecular and clinical remissions in multiple myeloma: role of autologous and allogeneic transplantation of hematopoietic cells.J Clin Oncol. 1999;17:208–2155.

    Article  PubMed  CAS  Google Scholar 

  34. Alyea EP, Weller E, Schlossman RL, et al. Comparison of autologous and allogeneic stem cell transplantation in patients with multiple myeloma (MM): impact of graft versus myeloma (GVM) on relapse [abstract].Blood. 2001;98:482a. Abstract 2014.

    Article  Google Scholar 

  35. Lokhorst HM, Segeren CM, Holt B, et al. T-cell depleted allogeneic stem cell transplantation as part of first line treatment of multiple myeloma is inferior to intensive treatment alone: results from a prospective donor versus no donor comparison of patients treated in the HOVON 24 study [abstract].Blood. 2001;98:481a. Abstract 2008.

    Google Scholar 

  36. Schaap N, Schattenberg A, Bär B, Preijers F, van de Wiel van Kemenade E, De Witte T. Induction of graft-versus-leukemia to prevent relapse after partially lymphocyte-depleted allogeneic bone marrow transplantation by pre-emptive donor leukocyte infusions.Leukemia. 2001;15:1339–1346.

    Article  PubMed  CAS  Google Scholar 

  37. Le Blanc R, Montminy-Métivier S, Bélanger R, et al. Allogeneic transplantation for multiple myeloma: further evidence for a GVHD-associated graft-versus-myeloma effect.Bone Marrow Transplant. 2001;28:841–848.

    Article  Google Scholar 

  38. Libura J, Hoffmann T, Passweg J, et al. Graft-versus-myeloma after withdrawal of immunosuppression following allogeneic peripheral stem cell transplantation.Bone Marrow Transplant. 1999;24:925–9277.

    Article  PubMed  CAS  Google Scholar 

  39. Bertz H, Burger JA, Kunzmann R, Mertelsmann R, Finke J. Adoptive immunotherapy for relapsed multiple myeloma after allogeneic bone marrow transplantation (BMT): evidence for a graftversus- myeloma effect.Leukemia. 1997;11:281–283.

    Article  PubMed  CAS  Google Scholar 

  40. Salama M, Nevill T, Marcellus D, et al. Donor leukocyte infusions for multiple myeloma.Bone Marrow Transplant. 2000;26:1179–11844.

    Article  PubMed  CAS  Google Scholar 

  41. Collins RH Jr, Shpilberg O, Drobyski WR, et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation.J Clin Oncol. 1997;15:433–444.

    Article  PubMed  Google Scholar 

  42. Alyea E, Ritz J. Induction of graft versus myeloma by donor lymphocyte infusions following allogeneic bone marrow transplant. In: Anderson KC, ed. Syllabus of the VI International Workshop on Multiple Myeloma 1997; June 14-18, 1997; Boston, Mass, USA.

  43. Mehta J, Singhal S. Graft-versus-myeloma [review].Bone Marrow Transplant. 1998;22:835–843.

    Article  PubMed  CAS  Google Scholar 

  44. Champlin R, Giralt S, Gajewski J, Hester J, Kürbling M, Deisseroth A. CD8 depleted donor lymphocytes for CML relapsing post BMT.Exp Hematol. 1995;23:939.

    Google Scholar 

  45. Molina A, Sahebi F, Maloney DG, et al. Non-myeloablative peripheral blood stem cell (PBSC) allografts following cytoreductive autotransplants for treatment of multiple myeloma (MM) [abstract].Blood. 2000;96:480a. Abstract 2063

    Google Scholar 

  46. Badros A, Barlogie B, Cottler-Fox M, et al. Improved outcome of allogeneic transplants in high risk multiple myeloma (MM) patients (pts) following non-myeloablative conditioning [abstract].Blood. 2001;98:414a. Abstract 1738.

    Article  Google Scholar 

  47. 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-versusmyeloma effect.Blood. 2001;98:934–939.

    Article  PubMed  CAS  Google Scholar 

  48. Bensinger WI, Buckner CD, Shannon-Dorcy K, et al. Transplantation of allogeneic CD34+ peripheral blood stem cells in patients with advanced hematologic malignancy.Blood. 1996;88:4132–4138.

    Article  PubMed  CAS  Google Scholar 

  49. Bensinger WI, Clift R, Martin P, et al. Allogeneic peripheral blood stem cell transplantation in patients with advanced hematologic malignancies: a retrospective comparison with marrow transplantation.Blood. 1996;88:2794–2800.

    Article  PubMed  CAS  Google Scholar 

  50. Majolino I, Corradini P, Scimè R, et al. Allogeneic transplantation of unmanipulated peripheral blood stem cells in patients with multiple myeloma.Bone Marrow Transplant. 1998;22:449–4555.

    Article  PubMed  CAS  Google Scholar 

  51. Majolino I, Corradini P, Santoro A, et al. In multiple myeloma (MM) allogeneic PBSC transplantation results in high rate of remission and low rate of recurrence [abstract].Blood. 2001;98:4199a. Abstract 1757.

    Google Scholar 

  52. Russell N, Bessell E, Stainer C, Haynes A, Das-Gupta E, Byrne J. Allogeneic haemopoietic stem cell transplantation for multiple myeloma or plasma cell leukaemia using fractionated total body radiation and high-dose melphalan conditioning.Acta Oncol. 2000; 39:837–841.

    Article  PubMed  CAS  Google Scholar 

  53. Storb R, Yu C, Sandmaier B, et al. Mixed hematopoietic chimerism after hematopoietic stem cell allografts.Transplant Proc. 1999;31:677–6788.

    Article  PubMed  CAS  Google Scholar 

  54. McSweeney PA, Niederwieser D, Shizuru JA, et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects.Blood. 2001;97:3390–3400.

    Article  PubMed  CAS  Google Scholar 

  55. Maloney DG, Sahebi F, Stockerl-Goldstein KE, et al. Combining an allogeneic graft-vs-myeloma effect with high-dose autologous stem cell rescue in the treatment of multiple myeloma [abstract].Blood. 2001;98:434a-435a. Abstract 1822.

    Google Scholar 

  56. Badros A, Barlogie B, Siegel E, et al. Improved outcome of allogeneic transplantation in high-risk multiple myeloma patients after nonmyeloablative conditioning.J Clin Oncol. 2002;20:1295–1303.

    Article  PubMed  Google Scholar 

  57. Krüger 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;100:755–7600.

    Article  CAS  Google Scholar 

  58. Krüger 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.

    Article  CAS  Google Scholar 

  59. Hoepfner S, Probst SM, Breitkreutz I, et al. Non-myeloablative allogeneic transplantation as part of salvage therapy for relapse of multiple myeloma after autologous transplantation [abstract].Blood. 2002;100:859a. Abstract 3387.

    Google Scholar 

  60. Einsele H, Schäfer HJ, Bader P, et al. Allografts after reduced intensity conditioning can induce long-term remission in patients with chemosensitive relapsed multiple myeloma (MM) [abstract].Blood. 2002;100:635a. Abstract 2499.

    Article  Google Scholar 

  61. Bensinger WI, Martin PJ, Storer B, et al. Transplantation of bone marrow as compared with peripheral-blood cells from HLAidentical relatives in patients with hematologic cancers.N Engl J Med. 2001;344:175–181.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to William I. Bensinger.

About this article

Cite this article

Bensinger, W.I. Recent Developments in Hematopoietic Stem Cell Transplantation for Multiple Myeloma. Int J Hematol 77, 232–238 (2003). https://doi.org/10.1007/BF02983779

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02983779

Key words

Navigation