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Mini–Midi–Maxi? How to harness the graft-versus-myeloma effect and target molecular remission after allogeneic stem cell transplantation

Abstract

Allogeneic stem cell transplantation in multiple myeloma after standard myeloablative conditioning induces a high rate of complete remissions, but long-term freedom from disease is achieved in 30–40% of the cases only. The therapeutic effect of allogeneic stem cell transplantation is due to cytotoxicity of high-dose chemotherapy and immune-mediated graft-versus-myeloma effect by donor T cells. Retrospective studies clearly suggest that both (a) reducing the intensity of high-dose chemotherapy by using reduced-intensity or non-myeloablative conditioning regimen or (b) reducing the immunotherapy of donor T cells by using T-cell depletion result in lower treatment-related morbidity and mortality, but also in higher rate of relapse. Therefore, this review will focus on potential strategies of how treatment-related morbidity and mortality might be kept low without an increased risk of relapse and how remission status after transplantation can be enhanced by using the newly established donor immunosystems after allografting as a platform for post-transplant treatment strategies with new drugs (thalidomide, lenalidomide, bortezomib) or immunotherapy (donor lymphocyte infusion, vaccination, tumor-specific T cells) in order to achieve remission on a molecular level, which seems to be a ‘conditio sine qua non’ to cure myeloma patients.

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References

  1. Corradini P, Voena C, Tarella C, Astolfi M, Ladetto M, Palumbo A et al. Molecular and clinical remissions in multiple myeloma: role of autologous and allogeneic transplantation of hematopoietic cells. J Clin Oncol 1999; 17: 208–215.

    Article  CAS  Google Scholar 

  2. Martinelli G, Terragna C, Zamagni E, Ronconi S, Tosi P, Lemoli RM et al. Molecular remission after allogeneic or autologous transplantation of hematopoietic stem cells for multiple myeloma. J Clin Oncol 2000; 18: 2273–2281.

    Article  CAS  Google Scholar 

  3. Bensinger WI, Buckner CD, Anasetti C, Clift R, Storb R, Barnett T et al. Allogeneic marrow transplantation for multiple myeloma: an analysis of risk factors on outcome. Blood 1996; 88: 2787–2793.

    CAS  Google Scholar 

  4. Hunter HM, Peggs K, Powles R, Rahemtulla A, Mahendra P, Cavenagh J et al. Clinical Trials Committee of the British Society of Blood and Marrow Transplantation (BSBMT). 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.

    Article  CAS  Google Scholar 

  5. Kröger N, Einsele H, Wolff D, Casper J, Freund M, Derigs G et al. German Study-group Multiple Myeloma (DSMM). Myeloablative intensified conditioning regimen with in vivo T-cell depletion (ATG) followed by allografting in patients with advanced multiple myeloma. A phase I/II study of the German Study-group Multiple Myeloma (DSMM). Bone Marrow Transplant 2003; 31: 973–979.

    Article  Google Scholar 

  6. Rabitsch W, Prinz E, Ackermann J, Wohrer S, Kaufmann H, Seidl S et al. Long-term follow up of patients with multiple myeloma after high-dose chemotherapy and allogeneic stem cell transplantation. Eur J Haematol 2004; 72: 26–31.

    Article  Google Scholar 

  7. Majolino I, Corradini P, Scime R, Santoro A, Tarella C, Cavallaro AM et al. Allogeneic transplantation of unmanipulated peripheral blood stem cells in patients with multiple myeloma. Bone Marrow Transplant 1998; 22: 449–455.

    Article  CAS  Google Scholar 

  8. Gahrton G, Svensson H, Cavo M, Apperly J, Bacigalupo A, Bjorkstrand B et al. European Group for Blood and Marrow Transplantation. Progress in allogenic bone marrow and peripheral blood stem cell transplantation for multiple myeloma: a comparison between transplants performed 1983–1993 and 1994–1998 at European Group for Blood and Marrow Transplantation centers. Br J Haematol 2001; 113: 209–216.

    Article  CAS  Google Scholar 

  9. Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, et al., (Intergroupe Francophone du Myelome). A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med 1996; 335: 91–97.

    Article  CAS  Google Scholar 

  10. Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG, et al., (Intergroupe Francophone du Myelome). Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 2003; 349: 2495–2502.

    Article  CAS  Google Scholar 

  11. Lokhorst HM, Wu K, Verdonck LF, Laterveer LL, van de Donk NW, van Oers MH et al. The occurrence of graft-versus-host disease is the major predictive factor for response to donor lymphocyte infusions in multiple myeloma. Blood 2004; 103: 4362–4364.

    Article  CAS  Google Scholar 

  12. Salama M, Nevill T, Marcellus D, Parker P, Johnson M, Kirk A et al. Donor leukocyte infusions for multiple myeloma. Bone Marrow Transplant 2000; 26: 1179–1184.

    Article  CAS  Google Scholar 

  13. Barnes DW, Corp MJ, Loutit JF, Neal FE . Treatment of murine leukaemia with X rays and homologous bone marrow; preliminary communication. BMJ 1956; 2: 626–627.

    Article  CAS  Google Scholar 

  14. Mathe G, Amiel JL, Schwarzenberg L, Cattan A, Schneider M . Adoptive immunotherapy of acute leukemia: experimental and clinical results. Cancer Res 1965; 25: 1525–1531.

    CAS  Google Scholar 

  15. Maloney DG, Molina AJ, Sahebi F, Stockerl-Goldstein KE, Sandmaier BM, Bensinger W et al. Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma. Blood 2003; 102: 3447–3454.

    Article  CAS  Google Scholar 

  16. Kröger N, Schwerdtfeger R, Kiehl M, Sayer HG, Renges H, Zabelina T 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.

    Article  Google Scholar 

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

    Article  Google Scholar 

  18. Giralt S, Aleman A, Anagnostopoulos A, Weber D, Khouri I, Anderlini P et al. Fludarabine/melphalan conditioning for allogeneic transplantation in patients with multiple myeloma. Bone Marrow Transplant 2002; 30: 367–373.

    Article  CAS  Google Scholar 

  19. Einsele H, Schafer HJ, Hebart H, Bader P, Meisner C, Plasswilm L et al. Follow-up of patients with progressive multiple myeloma undergoing allografts after reduced-intensity conditioning. Br J Haematol 2003; 121: 411–418.

    Article  Google Scholar 

  20. Mohty M, Boiron JM, Damaj G, Michallet AS, Bay JO, Faucher C et al. Graft-versus-myeloma effect following antithymocyte globulin-based reduced intensity conditioning allogeneic stem cell transplantation. Bone Marrow Transplant 2004; 34: 77–84.

    Article  CAS  Google Scholar 

  21. Gerull S, Goerner M, Benner A, Hegenbart U, Klein U, Schaefer H et al. Long-term outcome of nonmyeloablative allogeneic transplantation in patients with high-risk multiple myeloma. Bone Marrow Transplant 2005; 36: 963–969.

    Article  CAS  Google Scholar 

  22. Bjorkstrand BB, Ljungman P, Svensson H, Hermans J, Alegre A, Apperley J et al. Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma: a retrospective case-matched study from the European Group for Blood and Marrow Transplantation. Blood 1996; 88: 4711–4718.

    CAS  Google Scholar 

  23. Lokhorst HM, Segeren CM, Verdonck LF, van der Holt B, Raymakers R, van Oers MH, et al., Dutch-Belgian Hemato-Oncology Cooperative Group. Partially T-cell-depleted allogeneic stem-cell transplantation for first-line treatment of multiple myeloma: a prospective evaluation of patients treated in the phase III study HOVON 24 MM. J Clin Oncol 2003; 21: 1728–1733.

    Article  Google Scholar 

  24. Kröger N, Perez-Simon JA, Myint H, Klingemann H, Shimoni A, Nagler A et al. Relapse to prior autograft and chronic graft-versus-host disease are the strongest prognostic factors for outcome of melphalan/fludarabine-based dose-reduced allogeneic stem cell transplantation in patients with multiple myeloma. Biol Blood Marrow Transplant 2004; 10: 698–708.

    Article  Google Scholar 

  25. Crawley C, Iacobelli S, Bjorkstrand B, Apperley JF, Niederwieser D, Gahrton G . Reduced intensity conditioning for myeloma: lower non-relapse mortality but higher relapse rates compared to myeloablative conditioning. Blood 2007; 109: 3588–3594.

    Article  CAS  Google Scholar 

  26. Lee CK, Badros A, Barlogie B, Morris C, Zangari M, Fassas A et al. Prognostic factors in allogeneic transplantation for patients with high-risk multiple myeloma after reduced intensity conditioning. Exp Hematol 2003; 31: 73–80.

    Article  Google Scholar 

  27. Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myelome. Blood 2007; 109: 3489–3495.

    Article  CAS  Google Scholar 

  28. Gutierrez NC, Castellanos MV, Martin ML, Mateos MV, Hernandez JM, Fernandez M et al. GEM/PETHEMA Spanish Group. Prognostic and biological implications of genetic abnormalities in multiple myeloma undergoing autologous stem cell transplantation: t(4,14) is the most relevant adverse prognostic factor, whereas RB deletion as a unique abnormality is not associated with adverse prognosis. Leukemia 2007; 21: 143–150.

    Article  CAS  Google Scholar 

  29. Kröger N, Schilling G, Einsele H, Liebisch P, Shimoni A, Nagler A et al. Deletion of chromosome band 13q14 as detected by fluorescence in situ hybridization is a prognostic factor in patients with multiple myeloma who are receiving allogeneic dose-reduced stem cell transplantation. Blood 2004; 103: 4056–4061.

    Article  Google Scholar 

  30. McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, Maloney DG 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  CAS  Google Scholar 

  31. Carella AM, Beltrami G, Corsetti MT, Scalzulli P, Carella Jr AM, Musto P . A reduced intensity conditioning regimen for allografting following autografting is feasible and has strong anti-myeloma activity. Haematologica 2004; 89: 1534–1536.

    Google Scholar 

  32. Bruno B, Rotta M, Patriarca F, Mordini N, Allione B, Carnevale-Schianca F et al. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med 2007; 356: 1110–1120.

    Article  CAS  Google Scholar 

  33. Garban F, Attal M, Michallet M, Hulin C, Bourhis JH, Yakoub-Agha I 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.

    Article  CAS  Google Scholar 

  34. Mielcarek M, Martin PJ, Leisenring W, Flowers ME, Maloney DG, Sandmaier BM et al. Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation. Blood 2003; 102: 756–762.

    Article  CAS  Google Scholar 

  35. Perez-Simon JA, Diez-Campelo M, Martino R, Brunet S, Urbano A, Caballero MD ; et al. Influence of the intensity of the conditioning regimen on the characteristics of acute and chronic graft-versus-host disease after allogeneic transplantation. Br J Haematol 2005; 130: 394–403.

    Article  Google Scholar 

  36. Weiden PL, Flournoy N, Thomas ED, Prentice R, Fefer A, Buckner CD et al. Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts. N Engl J Med 1979; 300: 1068–1073.

    Article  CAS  Google Scholar 

  37. Weiden PL, Sullivan KM, Flournoy N, Storb R, Thomas ED . Antileukemic effect of chronic graft-versus-host disease: contribution to improved survival after allogeneic marrow transplantation. N Engl J Med 1981; 304: 1529–1533.

    Article  CAS  Google Scholar 

  38. Perez-Simon JA, Martino R, Alegre A, Tomas JF, De Leon A, Caballero D et al. Chronic but not acute graft-versus-host disease improves outcome in multiple myeloma patients after non-myeloablative allogeneic transplantation. Br J Haematol 2003; 121: 104–108.

    Article  Google Scholar 

  39. Bacigalupo A, Lamparelli T, Bruzzi P, Guidi S, Alessandrino PE, di Bartolomeo P et al. Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO). Blood 2001; 98: 2942–2947.

    Article  CAS  Google Scholar 

  40. Zander AR, Kröger N, Schleuning M, Finke J, Zabelina T, Beelen D et al. ATG as part of the conditioning regimen reduces transplant-related mortality (TRM) and improves overall survival after unrelated stem cell transplantation in patients with chronic myelogenous leukemia (CML). Bone Marrow Transplant 2003; 32: 355–361.

    Article  CAS  Google Scholar 

  41. Ayuk FA, Fang L, Fehse B, Zander AR, Kröger N . Antithymocyte globulin induces complement-dependent cell lysis and caspase-dependent apoptosis in myeloma cells. Exp Hematol 2005; 33: 1531–1536.

    Article  CAS  Google Scholar 

  42. Zand MS, Vo T, Pellegrin T, Felgar R, Liesveld JL, Ifthikharuddin JJ et al. Apoptosis and complement-mediated lysis of myeloma cells by polyclonal rabbit antithymocyte globulin. Blood 2006; 107: 2895–2903.

    Article  CAS  Google Scholar 

  43. Kröger N, Shaw B, Iacobelli S, Zabelina T, Peggs K, Shimoni A ; et al. Clinical Trial Committee of the British Society of Blood and Marrow Transplantation and the German Cooperative Transplant Group. Comparison between antithymocyte globulin and alemtuzumab and the possible impact of KIR-ligand mismatch after dose-reduced conditioning and unrelated stem cell transplantation in patients with multiple myeloma. Br J Haematol 2005; 129: 631–643.

    Article  Google Scholar 

  44. Barlogie B, Smith L, Alexanian R . Effective treatment of advanced multiple myeloma refractory to alkylating agents. N Engl J Med 1984; 310: 1353–1356.

    Article  CAS  Google Scholar 

  45. Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR ; Eastern Cooperative Oncology. 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.

    Article  CAS  Google Scholar 

  46. Harousseau JL, Attal M, Leleu X, Troncy J, Pegourie B, Stoppa AM ; et al. Bortezomib plus dexamethasone as induction treatment prior to autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: results of an IFM phase II study. Haematologica 2006; 91: 1498–1505.

    CAS  Google Scholar 

  47. O'Shea D, Giles C, Terpos E, Perz J, Politou M, Sana V et al. Predictive factors for survival in myeloma patients who undergo autologous stem cell transplantation: a single-centre experience in 211 patients. Bone Marrow Transplant 2006; 37: 731–737.

    Article  CAS  Google Scholar 

  48. Corradini P, Cavo M, Lokhorst H, Martinelli G, Terragna C, Majolino I et al., Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Molecular remission after myeloablative allogeneic stem cell transplantation predicts a better relapse-free survival in patients with multiple myeloma. Blood 2003; 102: 1927–1929.

    Article  CAS  Google Scholar 

  49. Hardan I, Rothman R, Gelibter A, Cohen N, Shimoni A, Sokolovsky M et al. Determination of chromosome 13 status in bone marrow cells of patients with multiple myeloma using combined morphologic and fluorescence in situ hybridization analysis. Exp Hematol 2004; 32: 254–260.

    Article  CAS  Google Scholar 

  50. Kröger N, Zagrivnaja M, Schwartz S, Badbaran A, Zabelina T, Lioznov M et al. Kinetics of plasma-cell chimerism after allogeneic stem cell transplantation by highly sensitive real-time PCR based on sequence polymorphism and its value to quantify minimal residual disease in patients with multiple myeloma. Exp Hematol 2006; 34: 688–694.

    Article  Google Scholar 

  51. Galimberti S, Benedetti E, Morabito F, Papineschi F, Callea V, Fazzi R et al. Prognostic role of minimal residual disease in multiple myeloma patients after non-myeloablative allogeneic transplantation. Leuk Res 2005; 29: 961–966.

    Article  CAS  Google Scholar 

  52. Matsui W, Huff CA, Wang Q, Malehorn MT, Barber J, Tanhehco Y et al. Characterization of clonogenic multiple myeloma cells. Blood 2004; 103: 2332–2336.

    Article  CAS  Google Scholar 

  53. Treon SP, Pilarski LM, Belch AR, Kelliher A, Preffer FI, Shima Y et al. CD20-directed serotherapy in patients with multiple myeloma: biologic considerations and therapeutic applications. J Immunother 2002; 25: 72–81.

    Article  Google Scholar 

  54. Moreau P, Voillat L, Benboukher L, Mathiot C, Dumontet C, Robillard N et al. Rituximab in CD20 positive multiple myeloma. Leukemia 2007; 21: 835–836.

    Article  CAS  Google Scholar 

  55. Attal M, Harousseau JL, Leyvraz S, Doyen C, Hulin C, Benboubker L, et al., (Intergroupe Francophone du Myelome). Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood 2006; 108: 3289–3294.

    Article  CAS  Google Scholar 

  56. Kolb HJ, Schattenberg A, Goldman JM, Hertenstein B, Jacobsen N, Arcese W, et al., European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. Blood 1995; 86: 2041–2050.

    CAS  Google Scholar 

  57. Verdonck LF, van Blokland WT, Bosboom-Kalsbeek EK, van Heugten HG, Tilanus MG, de Weger RA . Complete donor T cell chimerism is accomplished in patients transplanted with bone marrow grafts containing a fixed low number of T cells. Bone Marrow Transplant 1996; 18: 389–395.

    CAS  Google Scholar 

  58. 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 graft-versus-myeloma effect. Leukemia 1997; 11: 281–283.

    Article  CAS  Google Scholar 

  59. Lokhorst HM, Schattenberg A, Cornelissen JJ, Thomas LL, Verdonck LF . Donor leukocyte infusions are effective in relapsed multiple myeloma after allogeneic bone marrow transplantation. Blood 1997; 90: 4206–4211.

    CAS  Google Scholar 

  60. Ayuk F, Shimoni A, Nagler A, Schwerdtfeger R, Kiehl M, Sayer HG et al. Efficacy and toxicity of low-dose escalating donor lymphocyte infusion given after reduced intensity conditioning allograft for multiple myeloma. Leukemia 2004; 18: 659–662.

    Article  CAS  Google Scholar 

  61. Alyea E, Weller E, Schlossman R, Canning C, Webb I, Doss D 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.

    Article  CAS  Google Scholar 

  62. Peggs KS, Mackinnon S, Williams CD, D'Sa S, Thuraisundaram D, Kyriakou C et al. Reduced-intensity transplantation with in vivo T-cell depletion and adjuvant dose-escalating donor lymphocyte infusions for chemotherapy-sensitive myeloma: limited efficacy of graft-versus-tumor activity. Biol Blood Marrow Transplant 2003; 9: 257–265.

    Article  Google Scholar 

  63. Kröger N, Kruger W, Renges H, Zabelina T, Stute N, Jung R et al. Donor lymphocyte infusion enhances remission status in patients with persistent disease after allografting for multiple myeloma. Br J Haematol 2001; 112: 421–423.

    Article  Google Scholar 

  64. van de Donk NW, Kröger N, Hegenbart U, Corradini P, San Miguel JF, Goldschmidt H et al. Prognostic factors for donor lymphocyte infusions following non-myeloablative allogeneic stem cell transplantation in multiple myeloma. Bone Marrow Transplant 2006; 37: 1135–1141.

    Article  CAS  Google Scholar 

  65. Kröger N, Shimoni A, Zagrivnaja M, Ayuk F, Lioznov M, Schieder H et al. Low-dose thalidomide and donor lymphocyte infusion as adoptive immunotherapy after allogeneic stem cell transplantation in patients with multiple myeloma. Blood 2004; 104: 3361–3363.

    Article  Google Scholar 

  66. Sun K, Welniak LA, Panoskaltsis-Mortari A, O'Shaughnessy MJ, Liu H, Barao I et al. Inhibition of acute graft-versus-host disease with retention of graft-versus-tumor effects by the proteasome inhibitor bortezomib. Proc Natl Acad Sci USA 2004; 101: 8120–8125.

    Article  CAS  Google Scholar 

  67. Bruno B, Patriarca F, Sorasio R, Mattei D, Montefusco V, Peccatori J et al., Gruppo Italiano Trapianti di Midollo. Bortezomib with or without dexamethasone in relapsed multiple myeloma following allogeneic hematopoietic cell transplantation. Haematologica 2006; 91: 837–839.

    CAS  Google Scholar 

  68. Kröger N, Zabelina T, Ayuk F, Atanackovic D, Schieder H, Renges H et al. Bortezomib after dose-reduced allogeneic stem cell transplantation for multiple myeloma to enhance or maintain remission status. Exp Hematol 2006; 34: 770–775.

    Article  Google Scholar 

  69. van de Donk NW, Kröger N, Hegenbart U, Corradini P, San Miguel JF, Goldschmidt H et al. Remarkable activity of novel agents bortezomib and thalidomide in patients not responding to donor lymphocyte infusions following nonmyeloablative allogeneic stem cell transplantation in multiple myeloma. Blood 2006; 107: 3415–3416.

    Article  CAS  Google Scholar 

  70. Mohty M, Attal M, Marit G, Bulabois CE, Garban F, Gratecos N et al. Thalidomide salvage therapy following allogeneic stem cell transplantation for multiple myeloma: a retrospective study from the Intergroupe Francophone du Myelome (IFM) and the Societe Francaise de Greffe de Moelle et Therapie Cellulaire (SFGM-TC). Bone Marrow Transplant 2005; 35: 165–169.

    Article  CAS  Google Scholar 

  71. Byrne JL, Carter GI, Bienz N, Haynes AP, Russell NH . Adjuvant alpha-interferon improves complete remission rates following allogeneic transplantation for multiple myeloma. Bone Marrow Transplant 1998; 22: 639–643.

    Article  CAS  Google Scholar 

  72. Marijt WA, Heemskerk MH, Kloosterboer FM, Goulmy E, Kester MG, van der Hoorn MA et al. Hematopoiesis-restricted minor histocompatibility antigens HA-1- or HA-2-specific T cells can induce complete remissions of relapsed leukemia. Proc Natl Acad Sci USA 2003; 100: 2742–2747.

    Article  CAS  Google Scholar 

  73. Kwak LW, Taub DD, Duffey PL, Bensinger WI, Bryant EM, Reynolds CW et al. Transfer of myeloma idiotype-specific immunity from an actively immunised marrow donor. Lancet 1995; 345: 1016–1020.

    Article  CAS  Google Scholar 

  74. Neelapu SS, Munshi NC, Jagannath S, Watson TM, Pennington R, Reynolds C et al. Tumor antigen immunization of sibling stem cell transplant donors in multiple myeloma. Bone Marrow Transplant 2005; 36: 315–323.

    Article  CAS  Google Scholar 

  75. Atanackovic D, Arfsten J, Cao Y, Gnjatic S, Schnieders F, Bartels K et al. Cancer-testis antigens are commonly expressed in multiple myeloma and induce systemic immunity following allogeneic stem cell transplantation. Blood 2007; 109: 1103–1112.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank the staff of the BMT unit for providing excellent care to our patients and the medical technicians for their excellent work in the BMT laboratory. This work was supported by a grant from the ‘Deutsche Krebsgesellschaft e.V.’, the ‘Deutsche José Carreras Leukämie-Stiftung e.V.’ and the ‘Wilhelm Sander-Stiftung’.

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Kröger, N. Mini–Midi–Maxi? How to harness the graft-versus-myeloma effect and target molecular remission after allogeneic stem cell transplantation. Leukemia 21, 1851–1858 (2007). https://doi.org/10.1038/sj.leu.2404775

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