Skip to main content

Autologous Stem Cell Transplantation in the Management of Multiple Myeloma

  • Chapter
  • First Online:
Book cover Multiple Myeloma

Abstract

Autologous stem cell transplantation has been shown to improve the survival in patients with multiple myeloma. Seven randomized clinical trials have been reported demonstrating the superiority of stem cell transplantation in inducing disease responses, increasing complete remissions, and prolonging event-free survival (Table 10.1).

Three trials demonstrated significant prolongation of median survival in newly diagnosed patients [1]. The largest of these trials enrolled 401 patients and, compared with standard therapy, prolonged median survival by almost 1 year [2]. The available therapies in the era of these trials, however, did not include the novel agents, thalidomide, lenalidomide, and bortezomib, and some have questioned the rationale for stem cell transplantation with the advent of novel agents.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Matsui W, Borrello I, Mitsiades C. Autologous stem cell transplantation and multiple myeloma cancer stem cells. Biol Blood Marrow Transplant. 2012;18:S27–32.

    PubMed  Google Scholar 

  2. 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: 1875–83.

    PubMed  CAS  Google Scholar 

  3. Levy V, Katsahian S, Fermand JP, Mary JY, Chevret S. A meta-analysis on data from 575 patients with multiple myeloma randomly assigned to either high-dose therapy or conventional therapy. Medicine. 2005;84:250–60.

    PubMed  CAS  Google Scholar 

  4. Ferrara F, Palmieri S, Viola A, et al. Outpatient-based peripheral blood stem cell transplantation for patients with multiple myeloma. Hematol J. 2004;5: 222–6.

    PubMed  Google Scholar 

  5. Anderson KO, Giralt SA, Mendoza TR, et al. Symptom burden in patients undergoing autologous stem-cell transplantation. Bone Marrow Transplant. 2007;39:759–66.

    PubMed  CAS  Google Scholar 

  6. Knudsen LM, Nielsen B, Gimsing P, Geisler C. Autologous stem cell transplantation in multiple myeloma: outcome in patients with renal failure. Eur J Haematol. 2005;75:27–33.

    PubMed  Google Scholar 

  7. Bird JM, Fuge R, Sirohi B, et al. The clinical outcome and toxicity of high-dose chemotherapy and autologous stem cell transplantation in patients with myeloma or amyloid and severe renal impairment: a British Society of Blood and Marrow Transplantation study. Br J Haematol. 2006;134:385–90.

    PubMed  CAS  Google Scholar 

  8. Raab MS, Breitkreutz I, Hundemer M, et al. The outcome of autologous stem cell transplantation in patients with plasma cell disorders and dialysis-dependent renal failure. Haematologica. 2006;91: 1555–8.

    PubMed  CAS  Google Scholar 

  9. Parikh GC, Amjad AI, Saliba RM, et al. Autologous hematopoietic stem cell transplantation may reverse renal failure in patients with multiple myeloma. Biol Blood Marrow Transplant. 2009;15:812–6.

    PubMed  Google Scholar 

  10. Qazilbash MH, Saliba RM, Hosing C, et al. Autologous stem cell transplantation is safe and feasible in elderly patients with multiple myeloma. Bone Marrow Transplant. 2007;39:279–83.

    PubMed  CAS  Google Scholar 

  11. Offidani M, Leoni P, Corvatta L, et al. ThaDD plus high dose therapy and autologous stem cell transplantation does not appear superior to ThaDD plus maintenance in elderly patients with de novo multiple myeloma. Eur J Haematol. 2010;84:474–83.

    PubMed  CAS  Google Scholar 

  12. Kumar S, Perez WS, Zhang M-J, et al. Comparable outcomes in nonsecretory and secretory multiple myeloma after autologous stem cell transplantation. Biol Blood Marrow Transplant. 2008;14:1134–40.

    PubMed  Google Scholar 

  13. Kumar SK, Dingli D, Lacy MQ, et al. Outcome after autologous stem cell transplantation for multiple myeloma in patients with preceding plasma cell disorders. Br J Haematol. 2008;141:205–11.

    PubMed  Google Scholar 

  14. Nadal E, Gine E, Blade J, et al. High-dose therapy/autologous stem cell transplantation in patients with chemosensitive multiple myeloma: predictors of complete remission. Bone Marrow Transplant. 2004;33:61–4.

    PubMed  CAS  Google Scholar 

  15. Haessler J, Shaughnessy Jr JD, Zhan F, et al. Benefit of complete response in multiple myeloma limited to high-risk subgroup identified by gene expression profiling. Clin Cancer Res. 2007;13:7073–9.

    PubMed  CAS  Google Scholar 

  16. Lahuerta JJ, Mateos MV, Martinez-Lopez J, et al. Influence of pre- and post-transplantation responses on outcome of patients with multiple myeloma: sequential improvement of response and achievement of complete response are associated with longer survival. J Clin Oncol. 2008;26:5775–82.

    PubMed  Google Scholar 

  17. Harousseau J-L, Attal M, Avet-Loiseau H. The role of complete response in multiple myeloma. Blood. 2009;114:3139–46.

    PubMed  CAS  Google Scholar 

  18. Kim JS, Kim K, Cheong J-W, et al. Complete remission status before autologous stem cell transplantation is an important prognostic factor in patients with multiple myeloma undergoing upfront single autologous transplantation. Biol Blood Marrow Transplant. 2009;15:463–70.

    PubMed  CAS  Google Scholar 

  19. Kumar SK, Lacy MQ, Dispenzieri A, et al. Early versus delayed autologous transplantation after immunomodulatory agents-based induction therapy in patients with newly diagnosed multiple myeloma. Cancer. 2012;118:1585–92.

    PubMed  Google Scholar 

  20. Bergsagel PL. Individualizing therapy using molecular markers in multiple myeloma. Clin Lymphoma Myeloma. 2007;7 Suppl 4:S170–4.

    PubMed  CAS  Google Scholar 

  21. Shaughnessy Jr JD, Barlogie B. Using genomics to identify high-risk myeloma after autologous stem cell transplantation. Biol Blood Marrow Transplant. 2006;12:77–80.

    PubMed  CAS  Google Scholar 

  22. Kumar SK, Dingli D, Dispenzieri A, et al. Impact of pretransplant therapy in patients with newly diagnosed myeloma undergoing autologous SCT. Bone Marrow Transplant. 2008;41:1013–9.

    PubMed  CAS  Google Scholar 

  23. Korthals M, Sehnke N, Kronenwett R, et al. The level of minimal residual disease in the bone marrow of patients with multiple myeloma before high-dose therapy and autologous blood stem cell transplantation is an independent predictive parameter. Biol Blood Marrow Transplant. 2012;18:423–31.

    PubMed  Google Scholar 

  24. Cavo M, Zamagni E, Tosi P, et al. Superiority of thalidomide and dexamethasone over vincristine-doxorubicindexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma. Blood. 2005;106:35–9.

    PubMed  CAS  Google Scholar 

  25. Palumbo A, Avonto I, Bruno B, et al. Intermediate-dose melphalan (100 mg/m2)/bortezomib/thalidomide/dexamethasone and stem cell support in patients with refractory or relapsed myeloma. Clin Lymphoma Myeloma. 2006;6:475–7.

    PubMed  CAS  Google Scholar 

  26. Rosinol L, Oriol A, Mateos MV, et al. Phase II PETHEMA trial of alternating bortezomib and dexamethasone as induction regimen before autologous stem-cell transplantation in younger patients with multiple myeloma: efficacy and clinical implications of tumor response kinetics. J Clin Oncol. 2007;25: 4452–8.

    PubMed  CAS  Google Scholar 

  27. Oakervee H, Popat R, Cavenagh JD. Use of bortezomib as induction therapy prior to stem cell transplantation in frontline treatment of multiple myeloma: impact on stem cell harvesting and engraftment. Leuk Lymphoma. 2007;48:1910–21.

    PubMed  CAS  Google Scholar 

  28. Mellqvist U-H, Lenhoff S, Johnsen HE, et al. Cyclophosphamide plus dexamethasone is an efficient initial treatment before high-dose melphalan and autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: results of a randomized comparison with vincristine, doxorubicin, and dexamethasone. Cancer. 2008;112:129–35.

    PubMed  CAS  Google Scholar 

  29. Uy GL, Goyal SD, Fisher NM, et al. Bortezomib administered pre-auto-SCT and as maintenance therapy post transplant for multiple myeloma: a single institution phase II study. Bone Marrow Transplant. 2009;43:793–800.

    PubMed  CAS  Google Scholar 

  30. Cavo M, Di Raimondo F, Zamagni E, et al. Short-term thalidomide incorporated into double autologous stem-cell transplantation improves outcomes in comparison with double autotransplantation for multiple myeloma. J Clin Oncol. 2009;27:5001–7.

    PubMed  CAS  Google Scholar 

  31. Cavo M, Tacchetti P, Patriarca F, et al. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010;376:2075–85.

    PubMed  CAS  Google Scholar 

  32. Chim CS, Lie AKW, Chan EYT, et al. A staged approach with vincristine, adriamycin, and dexamethasone followed by bortezomib, thalidomide, and dexamethasone before autologous hematopoietic stem cell transplantation in the treatment of newly diagnosed multiple myeloma. Ann Hematol. 2010;89:1019–27.

    PubMed  CAS  Google Scholar 

  33. Corso A, Barbarano L, Mangiacavalli S, et al. Bortezomib plus dexamethasone can improve stem cell collection and overcome the need for additional chemotherapy before autologous transplant in patients with myeloma. Leuk Lymphoma. 2010;51: 236–42.

    PubMed  CAS  Google Scholar 

  34. Harousseau J-L, Attal M, Avet-Loiseau H, 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;28:4621–9.

    PubMed  CAS  Google Scholar 

  35. Palumbo A, Gay F, Falco P, et al. Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma patients. [Erratum appears in J Clin Oncol. 2010 May 1;28(13):2314]. J Clin Oncol. 2010;28:800–7.

    PubMed  CAS  Google Scholar 

  36. Tosi P, Zamagni E, Tacchetti P, et al. Thalidomide-dexamethasone as induction therapy before autologous stem cell transplantation in patients with newly diagnosed multiple myeloma and renal insufficiency. Biol Blood Marrow Transplant. 2010;16:1115–21.

    PubMed  CAS  Google Scholar 

  37. Moreau P, Avet-Loiseau H, Facon T, et al. Bortezomib plus dexamethasone versus reduced-dose bortezomib, thalidomide plus dexamethasone as induction treatment before autologous stem cell transplantation in newly diagnosed multiple myeloma. Blood. 2011;118:5752–8. quiz 5982.

    PubMed  CAS  Google Scholar 

  38. Morgan GJ, Davies FE, Gregory WM, et al. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results. Haematologica. 2012;97: 442–50.

    PubMed  CAS  Google Scholar 

  39. Kumar SK, Mikhael JR, Buadi FK, et al. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines. Mayo Clin Proc. 2009;84(12):1095–110.

    PubMed  CAS  Google Scholar 

  40. Porrata LF, Gastineau DA, Padley D, Bundy K, Markovic SN. Re-infused autologous graft natural killer cells correlates with absolute lymphocyte count recovery after autologous stem cell transplantation. Leuk Lymphoma. 2003;44:997–1000.

    PubMed  CAS  Google Scholar 

  41. Galimberti S, Morabito F, Guerrini F, et al. Peripheral blood stem cell contamination evaluated by a highly sensitive molecular method fails to predict outcome of autotransplanted multiple myeloma patients. Br J Haematol. 2003;120:405–12.

    PubMed  Google Scholar 

  42. Bourhis J-H, Bouko Y, Koscielny S, et al. Relapse risk after autologous transplantation in patients with newly diagnosed myeloma is not related with infused tumor cell load and the outcome is not improved by CD34+ cell selection: long term follow-up of an EBMT phase III randomized study. Haematologica. 2007;92:1083–90.

    PubMed  Google Scholar 

  43. Klaus J, Herrmann D, Breitkreutz I, et al. Effect of CD34 cell dose on hematopoietic reconstitution and outcome in 508 patients with multiple myeloma undergoing autologous peripheral blood stem cell transplantation. Eur J Haematol. 2007;78:21–8.

    PubMed  Google Scholar 

  44. Stiff PJ, Micallef I, Nademanee AP, et al. Transplanted CD34(+) cell dose is associated with long-term platelet count recovery following autologous peripheral blood stem cell transplant in patients with non-Hodgkin lymphoma or multiple myeloma. Biol Blood Marrow Transplant. 2011;17:1146–53.

    PubMed  CAS  Google Scholar 

  45. Jiang L, Malik S, Litzow M, et al. Hematopoietic stem cells from poor and good mobilizers are qualitatively equivalent. Transfusion. 2012;52:542–8.

    PubMed  CAS  Google Scholar 

  46. Petrucci MT, Avvisati G, La Verde G, et al. Intermediate-dose cyclophosphamide and granulocyte colony-stimulating factor is a valid alternative to high-dose cyclophosphamide for mobilizing peripheral blood CD34+ cells in patients with multiple myeloma. Acta Haematol. 2003;109:184–8.

    PubMed  CAS  Google Scholar 

  47. Gojo I, Guo C, Sarkodee-Adoo C, et al. High-dose cyclophosphamide with or without etoposide for mobilization of peripheral blood progenitor cells in patients with multiple myeloma: efficacy and toxicity. Bone Marrow Transplant. 2004;34:69–76.

    PubMed  CAS  Google Scholar 

  48. Breitkreutz I, Lokhorst HM, Raab MS, et al. Thalidomide in newly diagnosed multiple myeloma: influence of thalidomide treatment on peripheral blood stem cell collection yield. Leukemia. 2007;21:1294–9.

    PubMed  CAS  Google Scholar 

  49. Mark T, Stern J, Furst JR, et al. Stem cell mobilization with cyclophosphamide overcomes the suppressive effect of lenalidomide therapy on stem cell collection in multiple myeloma. Biol Blood Marrow Transplant. 2008;14:795–8.

    PubMed  CAS  Google Scholar 

  50. Nazha A, Cook R, Vogl DT, et al. Stem cell collection in patients with multiple myeloma: impact of induction therapy and mobilization regimen. Bone Marrow Transplant. 2011;46:59–63.

    PubMed  CAS  Google Scholar 

  51. Dingli D, Nowakowski GS, Dispenzieri A, et al. Cyclophosphamide mobilization does not improve outcome in patients receiving stem cell transplantation for multiple myeloma. Clin Lymphoma Myeloma. 2006;6:384–8.

    PubMed  CAS  Google Scholar 

  52. Zver S, Zadnik V, Bunc M, Rogel P, Cernelc P, Kozelj M. Cardiac toxicity of high-dose cyclophosphamide in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation. Int J Hematol. 2007;85:408–14.

    PubMed  CAS  Google Scholar 

  53. Ramzi M, Zakerinia M, Nourani H, Dehghani M, Vojdani R, Haghighinejad H. Non-cryopreserved hematopoietic stem cell transplantation in multiple myeloma, a single center experience. Clin Transplant. 2012;26:117–22.

    PubMed  Google Scholar 

  54. Jang G, Ko OB, Kim S, Lee DH, Huh J, Suh C. Prospective randomized comparative observation of single- versus split-dose lenograstim to enhance engraftment after autologous stem cell transplantation in patients with multiple myeloma or non-Hodgkin’s lymphoma. Transfusion. 2008;48(4):640–6.

    PubMed  Google Scholar 

  55. Bruns I, Steidl U, Kronenwett R, et al. A single dose of 6 or 12 mg of pegfilgrastim for peripheral blood progenitor cell mobilization results in similar yields of CD34+ progenitors in patients with multiple myeloma. Transfusion. 2006;46:180–5.

    PubMed  CAS  Google Scholar 

  56. Kroschinsky F, Holig K, Platzbecker U, et al. Efficacy of single-dose pegfilgrastim after chemotherapy for the mobilization of autologous peripheral blood stem cells in patients with malignant lymphoma or multiple myeloma. Transfusion. 2006;46:1417–23.

    PubMed  CAS  Google Scholar 

  57. Sebban C, Lefranc A, Perrier L, et al. A randomised phase II study of the efficacy, safety and cost-effectiveness of pegfilgrastim and filgrastim after autologous stem cell transplant for lymphoma and myeloma (PALM study). Eur J Cancer. 2012;48:713–20.

    PubMed  CAS  Google Scholar 

  58. Basak GW, Jaksic O, Koristek Z, et al. Haematopoietic stem cell mobilization with plerixafor and G-CSF in patients with multiple myeloma transplanted with autologous stem cells. Eur J Haematol. 2011;86:488–95.

    PubMed  CAS  Google Scholar 

  59. Attolico I, Pavone V, Ostuni A, et al. Plerixafor added to chemotherapy plus G-CSF is safe and allows adequate PBSC collection in predicted poor mobilizer patients with multiple myeloma or lymphoma. Biol Blood Marrow Transplant. 2012;18:241–9.

    PubMed  CAS  Google Scholar 

  60. Douglas KW, Parker AN, Hayden PJ, et al. Plerixafor for PBSC mobilisation in myeloma patients with advanced renal failure: safety and efficacy data in a series of 21 patients from Europe and the USA. Bone Marrow Transplant. 2012;47:18–23.

    PubMed  CAS  Google Scholar 

  61. Malard F, Kroger N, Gabriel IH, et al. Plerixafor for autologous peripheral blood stem cell mobilization in patients previously treated with fludarabine or lenalidomide. Biol Blood Marrow Transplant. 2012;18:314–7.

    PubMed  CAS  Google Scholar 

  62. Moreau P, Facon T, Attal M, et al. Comparison of 200 mg/m(2) melphalan and 8 Gy total body irradiation plus 140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myelome 9502 randomized trial. Blood. 2002;99:731–5.

    PubMed  CAS  Google Scholar 

  63. Dispenzieri A, Wiseman GA, Lacy MQ, et al. A phase I study of 153Sm-EDTMP with fixed high-dose melphalan as a peripheral blood stem cell conditioning regimen in patients with multiple myeloma. Leukemia. 2005;19:118–25.

    PubMed  CAS  Google Scholar 

  64. Dispenzieri A, Wiseman GA, Lacy MQ, et al. A phase II study of (153)Sm-EDTMP and high-dose melphalan as a peripheral blood stem cell conditioning regimen in patients with multiple myeloma. Am J Hematol. 2010;85:409–13.

    PubMed  CAS  Google Scholar 

  65. Somlo G, Spielberger R, Frankel P, et al. Total marrow irradiation: a new ablative regimen as part of tandem autologous stem cell transplantation for patients with multiple myeloma. Clin Cancer Res. 2011;17:174–82.

    PubMed  CAS  Google Scholar 

  66. Wong JYC, Rosenthal J, Liu A, Schultheiss T, Forman S, Somlo G. Image-guided total-marrow irradiation using helical tomotherapy in patients with multiple myeloma and acute leukemia undergoing hematopoietic cell transplantation. Int J Radiat Oncol Biol Phys. 2009;73:273–9.

    PubMed  Google Scholar 

  67. Fenk R, Schneider P, Kropff M, et al. High-dose idarubicin, cyclophosphamide and melphalan as conditioning for autologous stem cell transplantation increases treatment-related mortality in patients with multiple myeloma: results of a randomised study. Br J Haematol. 2005;130:588–94.

    PubMed  CAS  Google Scholar 

  68. Clopes A, Sureda A, Sierra J, et al. Absence of veno-occlusive disease in a cohort of multiple myeloma patients undergoing autologous stem cell transplantation with targeted busulfan dosage. Eur J Haematol. 2006;77:1–6.

    PubMed  CAS  Google Scholar 

  69. Blanes M, de la Rubia J, Lahuerta JJ, et al. Single daily dose of intravenous busulfan and melphalan as a conditioning regimen for patients with multiple myeloma undergoing autologous stem cell transplantation: a phase II trial. Leuk Lymphoma. 2009;50:216–22.

    PubMed  CAS  Google Scholar 

  70. Lahuerta JJ, Mateos MV, Martinez-Lopez J, et al. Busulfan 12 mg/kg plus melphalan 140 mg/m2 versus melphalan 200 mg/m2 as conditioning regimens for autologous transplantation in newly diagnosed multiple myeloma patients included in the PETHEMA/GEM2000 study. Haematologica. 2010;95:1913–20.

    PubMed  CAS  Google Scholar 

  71. Comenzo RL, Hassoun H, Kewalramani T, et al. Results of a phase I/II trial adding carmustine (300 mg/m2) to melphalan (200 mg/m2) in multiple myeloma patients undergoing autologous stem cell transplantation. Leukemia. 2005;20:345–9.

    Google Scholar 

  72. Lonial S, Kaufman J, Tighiouart M, et al. A phase I/II trial combining high-dose melphalan and autologous transplant with bortezomib for multiple myeloma: a dose- and schedule-finding study. Clin Cancer Res. 2010;16:5079–86.

    PubMed  CAS  Google Scholar 

  73. Beaven AW, Moore DT, Sharf A, Serody JS, Shea TC, Gabriel DA. Infusional mitoxantrone plus bolus melphalan as a stem cell transplant conditioning regimen for multiple myeloma. Cancer Invest. 2011;29:214–9.

    PubMed  CAS  Google Scholar 

  74. Qazilbash MH, Saliba RM, Nieto Y, et al. Arsenic trioxide with ascorbic acid and high-dose melphalan: results of a phase II randomized trial. Biol Blood Marrow Transplant. 2008;14:1401–7.

    PubMed  CAS  Google Scholar 

  75. Kazmi SMA, Saliba RM, Donato M, et al. Phase II trial of high-dose topotecan, melphalan and CY with autologous stem cell support for multiple myeloma. Bone Marrow Transplant. 2011;46:510–5.

    PubMed  CAS  Google Scholar 

  76. 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.

    PubMed  CAS  Google Scholar 

  77. Blijlevens N, Schwenkglenks M, Bacon P, et al. Prospective oral mucositis audit: oral mucositis in patients receiving high-dose melphalan or BEAM conditioning chemotherapy—European Blood and Marrow Transplantation Mucositis Advisory Group. J Clin Oncol. 2008;26:1519–25.

    PubMed  CAS  Google Scholar 

  78. Fassas ABT, Spencer T, Desikan R, et al. Cytotoxic chemotherapy following tandem autotransplants in multiple myeloma patients. Br J Haematol. 2002; 119:164–8.

    PubMed  Google Scholar 

  79. The Myeloma Trialists’ Collaborative Group. Interferon as therapy for multiple myeloma: an individual patient data overview of 24 randomized trials and 4012 patients. Br J Haematol. 2001;113:1020–34.

    Google Scholar 

  80. Stewart AK, Chen CI, Howson-Jan K, et al. Results of a multicenter randomized phase II trial of thalidomide and prednisone maintenance therapy for multiple myeloma after autologous stem cell transplant. Clin Cancer Res. 2004;10:8170–6.

    PubMed  CAS  Google Scholar 

  81. Barlogie B, Tricot G, Anaissie E, et al. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med. 2006;354:1021–30.

    PubMed  CAS  Google Scholar 

  82. Attal M, Harousseau J-L, Leyvraz S, et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006;108:3289–94.

    PubMed  CAS  Google Scholar 

  83. Martino M, Console G, Callea V, et al. Low tolerance and high toxicity of thalidomide as maintenance therapy after double autologous stem cell transplant in multiple myeloma patients. Eur J Haematol. 2007;78:35–40.

    PubMed  CAS  Google Scholar 

  84. Lokhorst H, van der Holt B, Zweegman S, et al. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010;115:1113–20.

    PubMed  CAS  Google Scholar 

  85. Lacy MQ, Mandrekar S, Dispenzieri A, et al. Idiotype-pulsed antigen-presenting cells following autologous transplantation for multiple myeloma may be associated with prolonged survival. Am J Hematol. 2009;84:799–802 [Erratum appears in Am J Hematol. 2010 Apr;85(4):309].

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  87. McCarthy PL, Owzar K, Hofmeister CC, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366:1770–81.

    PubMed  CAS  Google Scholar 

  88. Ladetto M, Pagliano G, Ferrero S, et al. Major tumor shrinking and persistent molecular remissions after consolidation with bortezomib, thalidomide, and dexamethasone in patients with autografted myeloma. J Clin Oncol. 2010;28:2077–84.

    PubMed  CAS  Google Scholar 

  89. Rifkin RM, Greenspan A, Schwerkoske JF, et al. A phase II open-label trial of bortezomib in patients with multiple myeloma who have undergone an autologous peripheral blood stem cell transplant and failed to achieve a complete response. Invest New Drugs. 2012;30:714–22.

    PubMed  CAS  Google Scholar 

  90. Sahebi F, Frankel PH, Farol L, et al. Sequential bortezomib, dexamethasone, and thalidomide maintenance therapy after single autologous peripheral stem cell transplantation in patients with multiple myeloma. Biol Blood Marrow Transplant. 2012;18:486–92.

    PubMed  CAS  Google Scholar 

  91. Neben K, Lokhorst HM, Jauch A, et al. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012;119:940–8.

    PubMed  CAS  Google Scholar 

  92. Sonneveld P, Schmidt-Wolf I, van der Holt B, 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.

    PubMed  CAS  Google Scholar 

  93. Attal M, Harousseau J-L, Facon T, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. [Erratum appears in N Engl J Med. 2004 Jun17;350(25):2628]. N Engl J Med. 2003;349:2495–502.

    PubMed  CAS  Google Scholar 

  94. Lahuerta JJ, Grande C, Martinez-Lopez J, et al. Tandem transplants with different high-dose regimens improve the complete remission rates in multiple myeloma. Results of a Grupo Espanol de Sindromes Linfoproliferativos/Trasplante Autologo de Medula Osea phase II trial. Br J Haematol. 2003;120:296–303.

    PubMed  CAS  Google Scholar 

  95. Galli M, Nicolucci A, Valentini M, et al. Feasibility and outcome of tandem stem cell autotransplants in multiple myeloma. Haematologica. 2005;90:1643–9.

    PubMed  CAS  Google Scholar 

  96. Moreau P, Hullin C, Garban F, et al. Tandem autologous stem cell transplantation in high-risk de novo multiple myeloma: final results of the prospective and randomized IFM 99-04 protocol. Blood. 2006;107:397–403.

    PubMed  CAS  Google Scholar 

  97. Barlogie B, Tricot GJ, van Rhee F, et al. Long-term outcome results of the first tandem autotransplant trial for multiple myeloma. Br J Haematol. 2006;135:158–64.

    PubMed  Google Scholar 

  98. Cavo M, Tosi P, Zamagni E, 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(17):2434–41.

    PubMed  Google Scholar 

  99. Corso A, Mangiacavalli S, Barbarano L, et al. Limited feasibility of double transplant in multiple myeloma: results of a multicenter study on 153 patients aged <65 years. Cancer. 2007;109:2273–8.

    PubMed  Google Scholar 

  100. Sunami K, Shinagawa K, Sawamura M, et al. Phase I/II study of tandem high-dose chemotherapy with autologous peripheral blood stem cell transplantation for advanced multiple myeloma. Int J Hematol. 2009;90:635–42.

    PubMed  CAS  Google Scholar 

  101. Novitzky N, Thomson J, Thomas V, du Toit C, Mohamed Z, McDonald A. Combined submyeloablative and myeloablative dose intense melphalan results in satisfactory responses with acceptable toxicity in patients with multiple myeloma. Biol Blood Marrow Transplant. 2010;16:1402–10.

    PubMed  CAS  Google Scholar 

  102. Blade J, Rosinol L. Advances in therapy of multiple myeloma. Curr Opin Oncol. 2008;20:697–704.

    PubMed  CAS  Google Scholar 

  103. Kumar A, Kharfan-Dabaja MA, Glasmacher A, Djulbegovic B. Tandem versus single autologous hematopoietic cell transplantation for the treatment of multiple myeloma: a systematic review and meta-analysis. J Natl Cancer Inst. 2009;101:100–6.

    PubMed  CAS  Google Scholar 

  104. Krivanova A, Hajek R, Krejci M, et al. Second autologous transplantation for multiple myeloma patients relapsing after the first autograft—a pilot study for the evaluation of experimental maintenance therapies. Report of the prospective non-randomized pilot study of the Czech Myeloma Group. Onkologie. 2004;27: 275–9.

    PubMed  CAS  Google Scholar 

  105. Jimenez-Zepeda VH, Mikhael J, Winter A, et al. Second autologous stem cell transplantation as salvage therapy for multiple myeloma: impact on progression-free and overall survival. Biol Blood Marrow Transplant. 2012;18:773–9.

    PubMed  Google Scholar 

  106. Burzynski JA, Toro JJ, Patel RC, et al. Toxicity of a second autologous peripheral blood stem cell transplant in patients with relapsed or recurrent multiple myeloma. Leuk Lymphoma. 2009;50:1442–7.

    PubMed  CAS  Google Scholar 

  107. Qazilbash MH, Saliba R, De Lima M, et al. Second autologous or allogeneic transplantation after the failure of first autograft in patients with multiple myeloma. Cancer. 2006;106:1084–9.

    PubMed  Google Scholar 

  108. 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;107:3474–80.

    PubMed  CAS  Google Scholar 

  109. Bruno B, Rotta M, Patriarca F, et al. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med. 2007;356:1110–20.

    PubMed  CAS  Google Scholar 

  110. Gahrton G, Iacobelli S, Bandini G, et al. Peripheral blood or bone marrow cells in reduced-intensity or myeloablative conditioning allogeneic HLA identical sibling donor transplantation for multiple myeloma. Haematologica. 2007;92:1513–8.

    PubMed  Google Scholar 

  111. 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;109:3588–94.

    PubMed  CAS  Google Scholar 

  112. 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;13:925–31.

    PubMed  Google Scholar 

  113. Levenga H, Levison-Keating S, Schattenberg AV, Dolstra H, Schaap N, Raymakers RA. 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;40:355–9.

    PubMed  CAS  Google Scholar 

  114. Rosinol L, Perez-Simon JA, Sureda A, 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.

    PubMed  CAS  Google Scholar 

  115. Bruno B, Rotta M, Patriarca F, et al. Nonmyeloablative allografting for newly diagnosed multiple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo. Blood. 2009;113:3375–82.

    PubMed  CAS  Google Scholar 

  116. Rotta M, Storer BE, Sahebi F, et al. Long-term outcome of patients with multiple myeloma after autologous hematopoietic cell transplantation and nonmyeloablative allografting. Blood. 2009;113:3383–91.

    PubMed  CAS  Google Scholar 

  117. Efebera YA, Qureshi SR, Cole SM, et al. Reduced-intensity allogeneic hematopoietic stem cell transplantation for relapsed multiple myeloma. Biol Blood Marrow Transplant. 2010;16:1122–9.

    PubMed  CAS  Google Scholar 

  118. Kroger N, Einsele H, Derigs G, Wandt H, Krull A, Zander A. Long-term follow-up of an intensified myeloablative conditioning regimen with in vivo T cell depletion followed by allografting in patients with advanced multiple myeloma. Biol Blood Marrow Transplant. 2010;16:861–4.

    PubMed  Google Scholar 

  119. Lokhorst H, Einsele H, Vesole D, et al. International Myeloma Working Group consensus statement regarding the current status of allogeneic stem-cell transplantation for multiple myeloma. J Clin Oncol. 2010;28:4521–30.

    PubMed  Google Scholar 

  120. Bjorkstrand B, Iacobelli S, Hegenbart U, et al. Tandem autologous/reduced-intensity conditioning allogeneic stem-cell transplantation versus autologous transplantation in myeloma: long-term follow-up. [Erratum appears in J Clin Oncol. 2011 Sep 20;29(27):3721]. J Clin Oncol. 2011;29:3016–22.

    PubMed  Google Scholar 

  121. Krishnan A, Pasquini MC, Logan B, 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.

    PubMed  Google Scholar 

  122. Roos-Weil D, Moreau P, Avet-Loiseau H, et al. Impact of genetic abnormalities after allogeneic stem cell transplantation in multiple myeloma: a report of the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire. Haematologica. 2011;96: 1504–11.

    PubMed  Google Scholar 

  123. Bashir Q, Khan H, Orlowski RZ, et al. Predictors of prolonged survival after allogeneic hematopoietic stem cell transplantation for multiple myeloma. Am J Hematol. 2012;87:272–6.

    PubMed  Google Scholar 

  124. El-Cheikh J, Crocchiolo R, Boher JM, et al. Comparable outcomes between unrelated and related donors after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation in patients with high-risk multiple myeloma. Eur J Haematol. 2012;88:497–503.

    PubMed  Google Scholar 

  125. Nishihori T, Kharfan-Dabaja MA, Ochoa-Bayona JL, Bazarbachi A, Pasquini M, Alsina M. Role of reduced intensity conditioning in allogeneic hematopoietic cell transplantation for patients with multiple myeloma. Hematol Oncol Stem Cell Ther. 2011;4:1–9.

    PubMed  CAS  Google Scholar 

  126. Patriarca F, Einsele H, Spina F, 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;18:617–26.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Morie A. Gertz M.D., M.A.C.P. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Mayo Foundation for Medical Education and Research

About this chapter

Cite this chapter

Gertz, M.A., Reeder, C.B. (2014). Autologous Stem Cell Transplantation in the Management of Multiple Myeloma. In: Gertz, M., Rajkumar, S. (eds) Multiple Myeloma. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8520-9_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-8520-9_10

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-8519-3

  • Online ISBN: 978-1-4614-8520-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics