Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Autologous hematopoietic cell transplantation in multiple myeloma

S Vincent Rajkumar, MD
Section Editors
Robert S Negrin, MD
Robert A Kyle, MD
Deputy Editor
Rebecca F Connor, MD


Autologous hematopoietic cell transplantation (HCT), performed either at the time of initial diagnosis or at relapse, is considered the standard of care for younger patients (less than 70 years of age) with newly diagnosed multiple myeloma (MM) (algorithm 1). While neither chemotherapy nor autologous HCT produces a cure, event-free survival and overall survival are prolonged following autologous HCT when compared with treatment with conventional chemotherapy alone.

As new chemotherapeutic agents (eg, bortezomib, thalidomide, lenalidomide) are incorporated into the initial treatment of MM, survival with chemotherapy alone is improving. Whether the use of these newer agents, alone or in combination, will delay or eliminate the need for HCT in patients with MM is not known at this time. In addition, survival with HCT is improving for certain populations with the incorporation of double (tandem) autologous HCT.

In contrast, allogeneic HCT has the potential for cure, although at a cost of increased treatment-related mortality. The use of allogeneic HCT for MM is discussed in detail separately. (See "Allogeneic hematopoietic cell transplantation in multiple myeloma".)

Practical issues regarding the use of autologous HCT in myeloma are presented here. Eligibility criteria for HCT, a comparison of HCT with other treatment strategies, and the initial chemotherapy choices for patients with myeloma are discussed separately. (See "Overview of the management of multiple myeloma" and "Selection of initial chemotherapy for symptomatic multiple myeloma".)

The term "hematopoietic cell transplantation" (HCT) will be used throughout this review as a general term to cover transplantation of progenitor (stem) cells from any source (eg, bone marrow, peripheral blood, cord blood). Otherwise, the source of such cells will be specified (eg, autologous peripheral blood progenitor cell transplantation). (See "Sources of hematopoietic stem cells".)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Mar 2017. | This topic last updated: Apr 25, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Kumar S, Giralt S, Stadtmauer EA, et al. Mobilization in myeloma revisited: IMWG consensus perspectives on stem cell collection following initial therapy with thalidomide-, lenalidomide-, or bortezomib-containing regimens. Blood 2009; 114:1729.
  2. Cavallo F, Bringhen S, Milone G, et al. Stem cell mobilization in patients with newly diagnosed multiple myeloma after lenalidomide induction therapy. Leukemia 2011; 25:1627.
  3. Moreau P, Attal M, Pégourié B, et al. Achievement of VGPR to induction therapy is an important prognostic factor for longer PFS in the IFM 2005-01 trial. Blood 2011; 117:3041.
  4. 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.
  5. Gertz MA, Kumar S, Lacy MQ, et al. Stem cell transplantation in multiple myeloma: impact of response failure with thalidomide or lenalidomide induction. Blood 2010; 115:2348.
  6. Rajkumar SV, Rosiñol L, Hussein M, et al. Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol 2008; 26:2171.
  7. Facon T, Mary JY, Pégourie B, et al. Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high-dose therapy. Blood 2006; 107:1292.
  8. 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.
  9. Rajkumar SV, Jacobus S, Callander N, et al. Phase III trial of lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed multiple myeloma (E4A03): a trial coordinated by the Eastern Cooperative Oncology Group (abstract). J Clin Oncol 2007; 25(18S):LBA8025.
  10. Lemoli RM, Martinelli G, Zamagni E, et al. Engraftment, clinical, and molecular follow-up of patients with multiple myeloma who were reinfused with highly purified CD34+ cells to support single or tandem high-dose chemotherapy. Blood 2000; 95:2234.
  11. Vesole DH, Tricot G, Jagannath S, et al. Autotransplants in multiple myeloma: what have we learned? Blood 1996; 88:838.
  12. Hosing C, Qazilbash MH, Kebriaei P, et al. Fixed-dose single agent pegfilgrastim for peripheral blood progenitor cell mobilisation in patients with multiple myeloma. Br J Haematol 2006; 133:533.
  13. Awan F, Kochuparambil ST, Falconer DE, et al. Comparable efficacy and lower cost of PBSC mobilization with intermediate-dose cyclophosphamide and G-CSF compared with plerixafor and G-CSF in patients with multiple myeloma treated with novel therapies. Bone Marrow Transplant 2013; 48:1279.
  14. Desikan KR, Tricot G, Munshi NC, et al. Preceding chemotherapy, tumour load and age influence engraftment in multiple myeloma patients mobilized with granulocyte colony-stimulating factor alone. Br J Haematol 2001; 112:242.
  15. http://www.fda.gov/cder/foi/label/2008/022311lbl.pdf (Accessed on January 05, 2008).
  16. DiPersio JF, Stadtmauer EA, Nademanee A, et al. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood 2009; 113:5720.
  17. Hartmann T, Hübel K, Monsef I, et al. Additional plerixafor to granulocyte colony-stimulating factors for haematopoietic stem cell mobilisation for autologous transplantation in people with malignant lymphoma or multiple myeloma. Cochrane Database Syst Rev 2015; :CD010615.
  18. Giralt S, Stadtmauer EA, Harousseau JL, et al. 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; 23:1904.
  19. Tricot G, Cottler-Fox MH, Calandra G. Safety and efficacy assessment of plerixafor in patients with multiple myeloma proven or predicted to be poor mobilizers, including assessment of tumor cell mobilization. Bone Marrow Transplant 2010; 45:63.
  20. Worel N, Rosskopf K, Neumeister P, et al. Plerixafor and granulocyte-colony-stimulating factor (G-CSF) in patients with lymphoma and multiple myeloma previously failing mobilization with G-CSF with or without chemotherapy for autologous hematopoietic stem cell mobilization: the Austrian experience on a named patient program. Transfusion 2011; 51:968.
  21. Mohty M, Hübel K, Kröger N, et al. Autologous haematopoietic stem cell mobilisation in multiple myeloma and lymphoma patients: a position statement from the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 2014; 49:865.
  22. Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med 2004; 351:1860.
  23. Hari P, Pasquini MC, Vesole DH. New questions about transplantation in multiple myeloma. Oncology (Williston Park) 2006; 20:1230.
  24. Berz D, McCormack EM, Winer ES, et al. Cryopreservation of hematopoietic stem cells. Am J Hematol 2007; 82:463.
  25. Zhou P, Zhang Y, Martinez C, et al. Melphalan-mobilized blood stem cell components contain minimal clonotypic myeloma cell contamination. Blood 2003; 102:477.
  26. Pilarski LM, Hipperson G, Seeberger K, et al. Myeloma progenitors in the blood of patients with aggressive or minimal disease: engraftment and self-renewal of primary human myeloma in the bone marrow of NOD SCID mice. Blood 2000; 95:1056.
  27. 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.
  28. Gazitt Y, Reading CC, Hoffman R, et al. Purified CD34+ Lin- Thy+ stem cells do not contain clonal myeloma cells. Blood 1995; 86:381.
  29. Tricot G, Gazitt Y, Leemhuis T, et al. Collection, tumor contamination, and engraftment kinetics of highly purified hematopoietic progenitor cells to support high dose therapy in multiple myeloma. Blood 1998; 91:4489.
  30. Stewart AK, Vescio R, Schiller G, et al. Purging of autologous peripheral-blood stem cells using CD34 selection does not improve overall or progression-free survival after high-dose chemotherapy for multiple myeloma: results of a multicenter randomized controlled trial. J Clin Oncol 2001; 19:3771.
  31. Bourhis JH, 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.
  32. Barbui AM, Galli M, Dotti G, et al. Negative selection of peripheral blood stem cells to support a tandem autologous transplantation programme in multiple myeloma. Br J Haematol 2002; 116:202.
  33. Mitterer M, Oduncu F, Lanthaler AJ, et al. The relationship between monoclonal myeloma precursor B cells in the peripheral blood stem cell harvests and the clinical response of multiple myeloma patients. Br J Haematol 1999; 106:737.
  34. Attal M, Lauwers-Cances V, Hulin C, et al. Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma. N Engl J Med 2017; 376:1311.
  35. Stewart AK, Bergsagel PL, Greipp PR, et al. A practical guide to defining high-risk myeloma for clinical trials, patient counseling and choice of therapy. Leukemia 2007; 21:529.
  36. Elice F, Raimondi R, Tosetto A, et al. Prolonged overall survival with second on-demand autologous transplant in multiple myeloma. Am J Hematol 2006; 81:426.
  37. Kumar S, Dingli D, Dispenzieri A, et al. Impact of additional cytoreduction following autologous SCT in multiple myeloma. Bone Marrow Transplant 2008; 42:259.
  38. 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 Myélome 9502 randomized trial. Blood 2002; 99:731.
  39. Palumbo A, Bringhen S, Bruno B, et al. Melphalan 200 mg/m(2) versus melphalan 100 mg/m(2) in newly diagnosed myeloma patients: a prospective, multicenter phase 3 study. Blood 2010; 115:1873.
  40. Anagnostopoulos A, Aleman A, Ayers G, et al. Comparison of high-dose melphalan with a more intensive regimen of thiotepa, busulfan, and cyclophosphamide for patients with multiple myeloma. Cancer 2004; 100:2607.
  41. 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.
  42. Roussel M, Moreau P, Huynh A, et al. Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myelome (IFM). Blood 2010; 115:32.
  43. Badros A, Barlogie B, Siegel E, et al. Results of autologous stem cell transplant in multiple myeloma patients with renal failure. Br J Haematol 2001; 114:822.
  44. Palumbo A, Triolo S, Argentino C, et al. Dose-intensive melphalan with stem cell support (MEL100) is superior to standard treatment in elderly myeloma patients. Blood 1999; 94:1248.
  45. Palumbo A, Bringhen S, Petrucci MT, et al. Intermediate-dose melphalan improves survival of myeloma patients aged 50 to 70: results of a randomized controlled trial. Blood 2004; 104:3052.
  46. Facon T, Mary JY, Hulin C, et al. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet 2007; 370:1209.
  47. Kumar SK, Dingli D, Lacy MQ, et al. Autologous stem cell transplantation in patients of 70 years and older with multiple myeloma: Results from a matched pair analysis. Am J Hematol 2008; 83:614.
  48. Schmitz N, Linch DC, Dreger P, et al. Randomised trial of filgrastim-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients. Lancet 1996; 347:353.
  49. Gertz MA, Ansell SM, Dingli D, et al. Autologous stem cell transplant in 716 patients with multiple myeloma: low treatment-related mortality, feasibility of outpatient transplant, and effect of a multidisciplinary quality initiative. Mayo Clin Proc 2008; 83:1131.
  50. Jones JA, Qazilbash MH, Shih YC, et al. In-hospital complications of autologous hematopoietic stem cell transplantation for lymphoid malignancies: clinical and economic outcomes from the Nationwide Inpatient Sample. Cancer 2008; 112:1096.
  51. Mellqvist UH, Gimsing P, Hjertner O, 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.
  52. 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.
  53. McCarthy PL, Owzar K, Hofmeister CC, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med 2012; 366:1770.
  54. Palumbo A, Cavallo F, Gay F, et al. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med 2014; 371:895.
  55. Musto P, Anderson KC, Attal M, et al. Second primary malignancies in multiple myeloma: an overview and IMWG consensus. Ann Oncol 2016.
  56. Attal M, Palumbo A, Holstein SA, et al. Lenalidomide maintenance after high-dose melphalan and autologous stem cell transplant in multiple myeloma: A meta-analysis of overall survival. J Clin Oncol 2016; 34:(suppl; abstr 8001).
  57. Sonneveld P, Schmidt-Wolf IG, 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.
  58. Feyler S, Rawstron A, Jackson G, et al. Thalidomide maintenance following high-dose therapy in multiple myeloma: a UK myeloma forum phase 2 study. Br J Haematol 2007; 139:429.
  59. Attal M, Harousseau JL, Leyvraz S, et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood 2006; 108:3289.
  60. Lokhorst HM, 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.
  61. Spencer A, Prince HM, Roberts AW, et al. Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol 2009; 27:1788.
  62. Barlogie B, Tricot G, Anaissie E, et al. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med 2006; 354:1021.
  63. Barlogie B, Pineda-Roman M, van Rhee F, et al. Thalidomide arm of Total Therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities. Blood 2008; 112:3115.
  64. Zangari M, van Rhee F, Anaissie E, et al. Eight-year median survival in multiple myeloma after total therapy 2: roles of thalidomide and consolidation chemotherapy in the context of total therapy 1. Br J Haematol 2008; 141:433.
  65. Barlogie B, Tricot G, Rasmussen E, et al. Total therapy 2 without thalidomide in comparison with total therapy 1: role of intensified induction and posttransplantation consolidation therapies. Blood 2006; 107:2633.
  66. Morgan GJ, Gregory WM, Davies FE, et al. The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis. Blood 2012; 119:7.
  67. Barlogie B, Attal M, Crowley J, et al. Long-term follow-up of autotransplantation trials for multiple myeloma: update of protocols conducted by the intergroupe francophone du myelome, southwest oncology group, and university of arkansas for medical sciences. J Clin Oncol 2010; 28:1209.
  68. 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.
  69. Stewart AK, Trudel S, Bahlis NJ, et al. A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial. Blood 2013; 121:1517.
  70. Usmani SZ, Sexton R, Hoering A, et al. Second malignancies in total therapy 2 and 3 for newly diagnosed multiple myeloma: influence of thalidomide and lenalidomide during maintenance. Blood 2012; 120:1597.
  71. Ludwig H, Durie BG, McCarthy P, et al. IMWG consensus on maintenance therapy in multiple myeloma. Blood 2012; 119:3003.
  72. Fassas AB, Spencer T, Desikan R, et al. Cytotoxic chemotherapy following tandem autotransplants in multiple myeloma patients. Br J Haematol 2002; 119:164.
  73. Paiva B, Vidriales MB, Cerveró J, et al. Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation. Blood 2008; 112:4017.
  74. Chanan-Khan AA, Giralt S. Importance of achieving a complete response in multiple myeloma, and the impact of novel agents. J Clin Oncol 2010; 28:2612.
  75. Martinez-Lopez J, Blade J, Mateos MV, et al. Long-term prognostic significance of response in multiple myeloma after stem cell transplantation. Blood 2011; 118:529.
  76. Harousseau JL, Avet-Loiseau H, Attal M, et al. Achievement of at least very good partial response is a simple and robust prognostic factor in patients with multiple myeloma treated with high-dose therapy: long-term analysis of the IFM 99-02 and 99-04 Trials. J Clin Oncol 2009; 27:5720.
  77. Kapoor P, Kumar SK, Dispenzieri A, et al. Importance of achieving stringent complete response after autologous stem-cell transplantation in multiple myeloma. J Clin Oncol 2013; 31:4529.
  78. Tannock I, Murphy K. Reflections on medical oncology: an appeal for better clinical trials and improved reporting of their results. J Clin Oncol 1983; 1:66.
  79. Rajkumar SV, Gahrton G, Bergsagel PL. Approach to the treatment of multiple myeloma: a clash of philosophies. Blood 2011; 118:3205.
  80. Hesse UJ, DeDecker C, Houtmeyers P, et al. Prospectively randomized trial using perioperative low-dose octreotide to prevent organ-related and general complications after pancreatic surgery and pancreatico-jejunostomy. World J Surg 2005; 29:1325.
  81. Kumar S, Mahmood ST, Lacy MQ, et al. Impact of early relapse after auto-SCT for multiple myeloma. Bone Marrow Transplant 2008; 42:413.
  82. Vangsted AJ, Klausen TW, Andersen NF, et al. Improved survival of multiple myeloma patients with late relapse after high-dose treatment and stem cell support, a population-based study of 348 patients in Denmark in 1994-2004. Eur J Haematol 2010; 85:209.
  83. Shah N, Ahmed F, Bashir Q, et al. Durable remission with salvage second autotransplants in patients with multiple myeloma. Cancer 2012; 118:3549.
  84. Cook G, Williams C, Brown JM, et al. High-dose chemotherapy plus autologous stem-cell transplantation as consolidation therapy in patients with relapsed multiple myeloma after previous autologous stem-cell transplantation (NCRI Myeloma X Relapse [Intensive trial]): a randomised, open-label, phase 3 trial. Lancet Oncol 2014; 15:874.
  85. Sellner L, Heiss C, Benner A, et al. Autologous retransplantation for patients with recurrent multiple myeloma: a single-center experience with 200 patients. Cancer 2013; 119:2438.