Biology of Blood and Marrow Transplantation
Volume 13, Issue 8 , Pages 877-885 , August 2007

Hematopoietic Stem Cell Transplantation in Multiple Myeloma

  • Shubham Pant

      Affiliations

    • Division of Hematology and Oncology, Ohio State University, Columbus, Ohio
  • ,
  • Edward A. Copelan

      Affiliations

    • Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Center, Cleveland Clinic Foundation
    • Corresponding Author InformationCorrespondence and reprint requests: Edward A. Copelan, MD, Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Center, Cleveland Clinic Foundation, 9500 Euclid Avenue R35, Cleveland, Ohio 44195.

Received 27 February 2007 ,Accepted 1 May 2007.

References 

  1. 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
  2. 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
  3. Barlogie B, Alexanian R. Therapy of primary resistant and relapsed multiple myeloma. Onkologie. 1986;9:210–214
  4. 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
  5. Fermand JP, Chevret S, Ravaud P, et al. High-dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma: results of a phase II trial involving 63 patients. Blood. 1993;82:2005–2009
  6. Gianni AM, Tarella C, Bregni M, et al. High-dose sequential chemoradiotherapy, a widely applicable regimen, confers survival benefit to patients with high-risk multiple myeloma. J Clin Oncol. 1994;12:503–509
  7. Cunningham D, Paz-Ares L, Gore ME, et al. High-dose melphalan for multiple myeloma: long-term follow-up data. J Clin Oncol. 1994;12:764–768
  8. Bjorkstrand B, Ljungman P, Bird JM, et al. Autologous stem cell transplantation in multiple myeloma: results of the European Group for Bone Marrow Transplantation. Stem Cells. 1995;13(Suppl 2):140–146
  9. Fermand JP, Katsahian S, Divine M, et al. High-dose therapy and autologous blood stem-cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65 years: long-term results of a randomized control trial from the Group Myelome-Autogreffe. J Clin Oncol. 2005;23:9227–9233
  10. 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;99:731–735
  11. Hahn T, Wingard JR, Anderson KC, et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of multiple myeloma: an evidence-based review. Biol Blood Marrow Transplant. 2003;9:4–37
  12. Barlogie B, Kyle RA, Anderson KC, 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
  13. Segeren CM, Sonneveld P, van der Holt B, 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
  14. Blade J, Rosinol L, Sureda A, 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
  15. Kumar S, Lacy MQ, Dispenzieri A, et al. High-dose therapy and autologous stem cell transplantation for multiple myeloma poorly responsive to initial therapy. Bone Marrow Transplant. 2004;34:161–167
  16. Koreth J, Cutler CS, Djulbegovic B, et al. High-dose therapy with single autologous transplantation versus chemotherapy for newly diagnosed multiple myeloma: a systematic review and meta-analysis of randomized controlled trials. Biol Blood Marrow Transplant. 2007;13:183–196
  17. Barlogie B, Jagannath S, Desikan KR, et al. Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood. 1999;93:55–65
  18. Barlogie B, Jagannath S, Vesole DH, et al. Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma. Blood. 1997;89:789–793
  19. Fermand J. High dose therapy supported with autologous blood stem cell transplantation multiple myeloma: long term follow up of the prospective studies of the MAG group. Haematologica. 2005;90:PL8.05
  20. Goldschmidt H. Single vs double high-dose therapy in multiple myeloma: second analysis of the GMMG-HD2 Trial. Haematologica. 2005;90:PL8.02
  21. 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
  22. Cavo MCC, Zamagni E, Tosi P, et al. Superiority of double over single autologous stem cell transplantation as first-line therapy for multiple myeloma. Blood. 2004;104:536
  23. Sonneveld , Segeren CM, Vellenga E, et al. Intensive versus double intensive therapy in untreated multiple myeloma: update analysis of the randomized phase III HOVON 24 study. PHvdB Haematologica. 2005;90:PL 8.01
  24. 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;135:158–164
  25. Desikan R, Barlogie B, Sawyer J, 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
  26. Tricot G, Sawyer JR, Jagannath 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
  27. Group MTC. Interferon as therapy for multiple myeloma: an individual patient data overview of 24 randomized trials and 4012 patients. Br J Haematol. 2001;113:1020–1034
  28. Bjorkstrand B, Svensson H, Goldschmidt H, et al. Alpha-interferon maintenance treatment is associated with improved survival after high-dose treatment and autologous stem cell transplantation in patients with multiple myeloma: a retrospective registry study from the European Group for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 2001;27:511–515
  29. Cunningham D, Powles R, Malpas J, 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
  30. Barlogie B, Tricot G, Anaissie E, et al. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med. 2006;354:1021–1030
  31. Attal M, Harousseau JL, Leyvraz S, et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006;108:3289–3294
  32. Goldschmidt H, Sonneveld P, Cremer FW, et al. Joint HOVON-50/GMMG-HD3 randomized trial on the effect of thalidomide as part of a high-dose therapy regimen and as maintenance treatment for newly diagnosed myeloma patients. Ann Hematol. 2003;82:654–659
  33. Barlogie BTG, Rasmussen E, Anaissie E, et al. Total therapy 3 (TT3) incorporating velcade (V) intro upfront management of multiple myeloma (MM): comparison with TT2 + thalidomide (T). Blood. 2005;106:1154
  34. Ries LAG EM, Kosary CL. SEER Cancer Statistics Review 1975-2000. Bethesda, MD: National Cancer Instuitute.
  35. Badros A, Barlogie B, Siegel E, et al. Autologous stem cell transplantation in elderly multiple myeloma patients over the age of 70 years. Br J Haematol. 2001;114:600–607
  36. 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;104:3052–3057
  37. Facon TMJ, Hulin C, Benboubker L, et al. Major superiority of melphalan-prednisone (MP) + thalidomide (THAL) over MP and autologous stem cell transplantation in the treatment of newly diagnosed elderly patients with multiple myeloma. Blood. 2005;106:780
  38. Fermand JP, 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
  39. Alexanian R, Weber D, Delasalle K, et al. Clinical outcomes with intensive therapy for patients with primary resistant multiple myeloma. Bone Marrow Transplant. 2004;34(3):229–234
  40. Vescio R, Schiller G, Stewart AK, et al. Multicenter phase III trial to evaluate CD34(+) selected versus unselected autologous peripheral blood progenitor cell transplantation in multiple myeloma. Blood. 1999;93:1858–1868
  41. Alici E, Bjorkstrand B, Treschow A, et al. Long-term follow-up of gene-marked CD34(+) cells after autologous stem cell transplantation for multiple myeloma. Cancer Gene Ther. 2007;14:227–232
  42. Gulbrandsen N, Wisloff F, Brinch L, et al. Health-related quality of life in multiple myeloma patients receiving high-dose chemotherapy with autologous blood stem-cell support. Med Oncol. 2001;18:65–77
  43. Henon P, Donatini B, Eisenmann JC, et al. Comparative survival, quality of life and cost-effectiveness of intensive therapy with autologous blood cell transplantation or conventional chemotherapy in multiple myeloma. Bone Marrow Transplant. 1995;16:19–25
  44. Uyl-de Groot CA, Ossenkoppele GJ, van Riet AA, Rutten FF. The costs of peripheral blood progenitor cell reinfusion mobilised by granulocyte colony-stimulating factor following high dose melphalan as compared with conventional therapy in multiple myeloma. Eur J Cancer. 1994;30A:457–459
  45. Gulbrandsen N, Wisloff F, Nord E, et al. Cost-utility analysis of high-dose melphalan with autologous blood stem cell support vs. melphalan plus prednisone in patients younger than 60 years with multiple myeloma. Eur J Haematol. 2001;66:328–336
  46. Gahrton G, Tura S, Ljungman P, et al. Allogeneic bone marrow transplantation in multiple myeloma (European Group for Bone Marrow Transplantation). N Engl J Med. 1991;325:1267–1273
  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-versus-myeloma effect. Blood. 2001;98:934–939
  48. van Bergen C, Kester M, Jedema I, et al. Multiple myeloma reactive T cells recognize an activation induced minor histocompatibility antigen encoded by the ATP dependent interferon responsive (ADIR) gene. Blood. 2007;(Jan 18, Published ahead of print)
  49. Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med. 2006;354:1813–1826
  50. 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
  51. 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
  52. 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
  53. Ballen KK, King R, Carston M, et al. Outcome of unrelated transplants in patients with multiple myeloma. Bone Marrow Transplant. 2005;35:675–681
  54. 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
  55. Majolino I, Corradini P, Scime R, et al. Allogeneic transplantation of unmanipulated peripheral blood stem cells in patients with multiple myeloma. Bone Marrow Transplant. 1998;22:449–455
  56. Radich JP, Gooley T, Bensinger W, et al. HLA-matched related hematopoietic cell transplantation for chronic-phase CML using a targeted busulfan and cyclophosphamide preparative regimen. Blood. 2003;102:31–35
  57. Kashyap A, Wingard J, Cagnoni P, et al. Intravenous versus oral busulfan as part of a busulfan/cyclophosphamide preparative regimen for allogeneic hematopoietic stem cell transplantation: decreased incidence of hepatic venoocclusive disease (HVOD), HVOD-related mortality, and overall 100-day mortality. Biol Blood Marrow Transplant. 2002;8:493–500
  58. Clopes A, Sureda A, Sierra J, et al. Absence of veno-occlussive disease in a cohort of multiple myeloma patients undergoing autologous stem cell transplantation with targeted busulfan dosage. Eur J Haematol. 2006;77:1–6
  59. 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
  60. Bensinger WI. The current status of reduced-intensity allogeneic hematopoietic stem cell transplantation for multiple myeloma. Leukemia. 2006;20:1683–1689
  61. 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
  62. Lee CK, Badros A, Barlogie B, et al. Prognostic factors in allogeneic transplantation for patients with high-risk multiple myeloma after reduced intensity conditioning. Exp Hematol. 2003;31:73–80
  63. 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
  64. 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
  65. 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
  66. 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
  67. Kyle RA. Five decades of therapy for multiple myeloma: a paradigm for therapeutic models. Leukemia. 2005;19:910–912
  68. 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
  69. Cavo M, Galieni P, Tassi C, et al. M-2 protocol for melphalan-resistant and relapsing multiple myeloma. Eur J Haematol. 1988;40:168–173
  70. Alexanian R, Barlogie B, Dixon D. High-dose glucocorticoid treatment of resistant myeloma. Ann Intern Med. 1986;105:8–11
  71. Alexanian R, Barlogie B, Ventura G. Chemotherapy for resistant and relapsing multiple myeloma. Eur J Haematol. 1989;51(Suppl):140–144
  72. Alexanian R, Dimopoulos MA, Delasalle K, Barlogie B. Primary dexamethasone treatment of multiple myeloma. Blood. 1992;80:887–890
  73. 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
  74. 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;106:35–39
  75. Palumbo A, Bringhen S, Caravita T, et al. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet. 2006;367:825–831
  76. 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
  77. Palumbo A, Ambrosini MT, Benevolo G, et al. Bortezomib, melphalan, prednisone and thalidomide for relapsed multiple myeloma. Blood. 2007;109:2767–2772
  78. Blade J, Lopez-Guillermo A, Bosch F, et al. Impact of response to treatment on survival in multiple myeloma: results in a series of 243 patients. Br J Haematol. 1994;88:117–121
  79. Durie BG, Jacobson J, Barlogie B, Crowley J. Magnitude of response with myeloma frontline therapy does not predict outcome: importance of time to progression in southwest oncology group chemotherapy trials. J Clin Oncol. 2004;22:1857–1863
  80. Wang MDK, Thomas S, Giralt S, et al. Complete remission represents the major surrogate marker of long survival in multiple myeloma. Blood. 2006;108:
  81. Huff CA, Matsui W, Smith BD, Jones RJ. The paradox of response and survival in cancer therapeutics. Blood. 2006;107:431–434
  82. Jones RJ, Matsui W. Cancer stem cells: from bench to bedside. Biol Blood Marrow Transplant. 2007;13(Suppl 1):47–52
  83. Matsui W, Huff CA, Wang Q, et al. Characterization of clonogenic multiple myeloma cells. Blood. 2004;103:2332–2336
  84. Peacock CD, Wang Q, Gesell GS, et al. Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. Proc Natl Acad Sci USA. 2007;104:4048–4053
  85. Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer. 2005;5:275–284
  86. Matsui W, Huff CA, Wang Q, Barber JP, Smith BD, Jones RJ. Multiple myeloma stem cells and plasma cells display distinct drug sensitivities. Blood. 2004;204:679a
  87. Greipp PR, San Miguel J, Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23:3412–3420
  88. Avet-Loiseau H, Attal M, Moreau P, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myelome. Blood. 2007;109:3489–3495
  89. Fonseca R, Blood EA, Oken MM, et al. Myeloma and the t(11;14)(q13;q32); evidence for a biologically defined unique subset of patients. Blood. 2002;99:3735–3741
  90. Stewart AK, Fonseca R. Prognostic and therapeutic significance of myeloma genetics and gene expression profiling. J Clin Oncol. 2005;23:6339–6344
  91. Chang H, Trieu Y, Qi X, et al. Bortezomib therapy response is independent of cytogenetic abnormalities in relapsed/refractory multiple myeloma. Leuk Res. 2006;
  92. Jagannath S, Richardson PG, Sonneveld P, et al. Bortezomib appears to overcome the poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials. Leukemia. 2007;21:151–157

PII: S1083-8791(07)00273-X

doi: 10.1016/j.bbmt.2007.05.002

Biology of Blood and Marrow Transplantation
Volume 13, Issue 8 , Pages 877-885 , August 2007