Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Full-intensity and reduced-intensity allogeneic stem cell transplantation in AML

Bone Marrow Transplantation volume 41, pages 415–423 (2008)Cite this article

Abstract

Allogeneic stem cell transplantation represents the most active form of anti-leukaemic therapy in acute myeloid leukaemia (AML). Advances in transplant technology and supportive care have resulted in improved outcomes in patients allografted using a myeloablative conditioning regimen. At the same time the use of reduced-intensity conditioning regimens has allowed an immunologically mediated graft-versus-leukaemia effect to be exploited in older patients who were previously ineligible for transplantation on the grounds of age or comorbidity. This coupled with the increased availability of alternative stem cell sources, in the form of either unrelated or cord blood donations, has established allogeneic transplantation as a key therapeutic strategy in the treatment of both younger and older adults with AML.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Gratwohl A, Baldomero H, Frauendorfer K, Urbano-Ispizua A . EBMT activity survey 2004 and changes in disease indication over the past 15 years. Bone Marrow Transplantation 2006; 37: 1069–1085.

    CAS  PubMed  Google Scholar 

  2. Buchner T, Berdel WE, Wormann B, Schoch C, Haferlach T, Schnittger S et al. Treatment of older patients with AML. Crit Rev Oncol Hematol 2005; 56: 247–259.

    PubMed  Google Scholar 

  3. Leith CP, Kopecky KJ, Godwin J, McConnell T, Slovak ML, Chen IM et al. Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group study. Blood 1997; 89: 3323–3329.

    CAS  PubMed  Google Scholar 

  4. Grimwade D, Walker H, Harrison G, Oliver F, Chatters S, Harrison CJ et al. The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood 2001; 98: 1312–1320.

    CAS  PubMed  Google Scholar 

  5. Frohling S, Schlenk RF, Kayser S, Morhardt M, Benner A, Dohner K et al. Cytogenetics and age are major determinants of outcome in intensively treated acute myeloid leukemia patients older than 60 years: results from AMLSG trial AML HD98-B. Blood 2006; 108: 3280–3288.

    CAS  PubMed  Google Scholar 

  6. Cornelissen JJ, van Putten WL, Verdonck LF, Theobald M, Jacky E, Daenen SM et al. Results of a HOVON/SAKK donor versus no-donor analysis of myeloablative HLA-identical sibling stem cell transplantation in first remission acute myeloid leukemia in young and middle-aged adults: benefits for whom? Blood 2007; 109: 3658–3666.

    CAS  PubMed  Google Scholar 

  7. Blaise D, Bay JO, Faucher C, Michallet M, Boiron JM, Choufi B et al. Reduced-intensity preparative regimen and allogeneic stem cell transplantation for advanced solid tumors. Blood 2004; 103: 435–441.

    CAS  PubMed  Google Scholar 

  8. de Lima M, Anagnostopoulos A, Munsell M, Shahjahan M, Ueno N, Ippoliti C et al. Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. Blood 2004; 104: 865–872.

    CAS  PubMed  Google Scholar 

  9. Hegenbart U, Niederwieser D, Sandmaier BM, Maris MB, Shizuru JA, Greinix H et al. Treatment for acute myelogenous leukemia by low-dose, total-body, irradiation-based conditioning and hematopoietic cell transplantation from related and unrelated donors. J Clin Oncol 2006; 24: 444–453.

    CAS  PubMed  Google Scholar 

  10. Tauro S, Craddock C, Peggs K, Begum G, Mahendra P, Cook G et al. Allogeneic stem-cell transplantation using a reduced-intensity conditioning regimen has the capacity to produce durable remissions and long-term disease-free survival in patients with high-risk acute myeloid leukemia and myelodysplasia. J Clin Oncol 2005; 23: 9387–9393.

    CAS  PubMed  Google Scholar 

  11. Lacerda JF, Martins C, Lourenco F, Carmo JA, Juncal C, Oliveira JJ et al. Unrelated stem cell transplantation after a reduced intensity conditioning regimen containing high-dose thymoglobulin leads to controllable graft-versus-host disease. Biol Blood Marrow Transplant 2007; 13: 494–497.

    CAS  PubMed  Google Scholar 

  12. Chakraverty R, Peggs K, Chopra R, Milligan DW, Kottaridis PD, Verfuerth S et al. Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen. Blood 2002; 99: 1071–1078.

    CAS  PubMed  Google Scholar 

  13. Bertz H, Potthoff K, Finke J . Allogeneic stem-cell transplantation from related and unrelated donors in older patients with myeloid leukemia. J Clin Oncol 2003; 21: 1480–1484.

    PubMed  Google Scholar 

  14. Druker BJ, Guilhot F, O'Brien SG, Gathmann I, Kantarjian H, Gattermann N et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006; 355: 2408–2417.

    CAS  PubMed  Google Scholar 

  15. Frohling S, Scholl C, Gilliland DG, Levine RL . Genetics of myeloid malignancies: pathogenetic and clinical implications. J Clin Oncol 2005; 23: 6285–6295.

    CAS  PubMed  Google Scholar 

  16. Bullinger L, Valk PJ . Gene expression profiling in acute myeloid leukemia. J Clin Oncol 2005; 23: 6296–6305.

    CAS  PubMed  Google Scholar 

  17. Knapper S, Burnett AK, Littlewood T, Kell WJ, Agrawal S, Chopra R et al. A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy. Blood 2006; 108: 3262–3270.

    CAS  PubMed  Google Scholar 

  18. Lancet JE, Gojo I, Gotlib J, Feldman EJ, Greer J, Liesveld JL et al. A phase 2 study of the farnesyltransferase inhibitor tipifarnib in poor-risk and elderly patients with previously untreated acute myelogenous leukemia. Blood 2007; 109: 1387–1394.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Valk PJ, Verhaak RG, Beijen MA, Erpelinck CA, Barjesteh van Waalwijk van Doorn-Khosrovani S, Boer JM et al. Prognostically useful gene-expression profiles in acute myeloid leukemia. N Engl J Med 2004; 350: 1617–1628.

    CAS  PubMed  Google Scholar 

  20. Tallman MS, Gilliland DG, Rowe JM . Drug therapy for acute myeloid leukemia. Blood 2005; 106: 1154–1163.

    CAS  PubMed  Google Scholar 

  21. Bonnet D, Dick JE . Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997; 3: 730–737.

    CAS  PubMed  Google Scholar 

  22. Krivtsov AV, Twomey D, Feng Z, Stubbs MC, Wang Y, Faber J et al. Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature 2006; 442: 818–822.

    CAS  PubMed  Google Scholar 

  23. Kirstetter P, Anderson K, Porse BT, Jacobsen SE, Nerlov C . Activation of the canonical Wnt pathway leads to loss of hematopoietic stem cell repopulation and multilineage differentiation block. Nat Immunol 2006; 7: 1048–1056.

    CAS  PubMed  Google Scholar 

  24. Guzman ML, Neering SJ, Upchurch D, Grimes B, Howard DS, Rizzieri DA et al. Nuclear factor-kappaB is constitutively activated in primitive human acute myelogenous leukemia cells. Blood 2001; 98: 2301–2307.

    CAS  PubMed  Google Scholar 

  25. Guzman ML, Swiderski CF, Howard DS, Grimes BA, Rossi RM, Szilvassy SJ et al. Preferential induction of apoptosis for primary human leukemic stem cells. Proc Natl Acad Sci USA 2002; 99: 16220–16225.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Xu Q, Thompson JE, Carroll M . mTOR regulates cell survival after etoposide treatment in primary AML cells. Blood 2005; 106: 4261–4268.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Sullivan KM, Weiden PL, Storb R, Witherspoon RP, Fefer A, Fisher L et al. Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia. Blood 1989; 73: 1720–1728.

    CAS  PubMed  Google Scholar 

  28. 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.

    CAS  PubMed  Google Scholar 

  29. Weaver CH, Clift RA, Deeg HJ, Storb R, Appelbaum FR, Bensinger W et al. Effect of graft-versus-host disease prophylaxis on relapse in patients transplanted for acute myeloid leukemia. Bone Marrow Transplantation 1994; 14: 885–893.

    CAS  PubMed  Google Scholar 

  30. Bacigalupo A, Van Lint MT, Occhini D, Gualandi F, Lamparelli T, Sogno G et al. Increased risk of leukemia relapse with high-dose cyclosporine A after allogeneic marrow transplantation for acute leukemia. Blood 1991; 77: 1423–1428.

    CAS  PubMed  Google Scholar 

  31. Bacigalupo A, Vitale V, Corvo R, Barra S, Lamparelli T, Gualandi F et al. The combined effect of total body irradiation (TBI) and cyclosporin A (CyA) on the risk of relapse in patients with acute myeloid leukaemia undergoing allogeneic bone marrow transplantation. Br J Haematol 2000; 108: 99–104.

    CAS  PubMed  Google Scholar 

  32. Greiner J, Schmitt M, Li L, Giannopoulos K, Bosch K, Schmitt A et al. Expression of tumor-associated antigens in acute myeloid leukemia: implications for specific immunotherapeutic approaches. Blood 2006; 108: 4109–4117.

    CAS  PubMed  Google Scholar 

  33. Scheibenbogen C, Letsch A, Thiel E, Schmittel A, Mailaender V, Baerwolf S et al. CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia. Blood 2002; 100: 2132–2137.

    CAS  PubMed  Google Scholar 

  34. Di Terlizzi S, Zino E, Mazzi B, Magnani C, Tresoldi C, Perna SK et al. Therapeutic and diagnostic applications of minor histocompatibility antigen HA-1 and HA-2 disparities in allogeneic hematopoietic stem cell transplantation: a survey of different populations. Biol Blood Marrow Transplant 2006; 12: 95–101.

    CAS  PubMed  Google Scholar 

  35. Mutis T, Verdijk R, Schrama E, Esendam B, Brand A, Goulmy E . Feasibility of immunotherapy of relapsed leukemia with ex vivo-generated cytotoxic T lymphocytes specific for hematopoietic system-restricted minor histocompatibility antigens. Blood 1999; 93: 2336–2341.

    CAS  PubMed  Google Scholar 

  36. Rezvani K, Yong AS, Savani BN, Mielke S, Keyvanfar K, Gostick E et al. Graft-versus-leukemia effects associated with detectable Wilms tumor-1 specific T lymphocytes following allogeneic stem cell transplantation for acute lymphoblastic leukemia (ALL). Blood 2007; 110: 1924–1932.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Xue SA, Gao L, Hart D, Gillmore R, Qasim W, Thrasher A et al. Elimination of human leukemia cells in NOD/SCID mice by WT1-TCR gene-transduced human T cells. Blood 2005; 106: 3062–3067.

    CAS  PubMed  Google Scholar 

  38. Vicente D, Lamparelli T, Gualandi F, Occhini D, Raiola AM, Ibatici A et al. Improved outcome in young adults with de novo acute myeloid leukemia in first remission, undergoing an allogeneic bone marrow transplant. Bone Marrow Transplantation 2007; 40: 349–354.

    CAS  PubMed  Google Scholar 

  39. Gorin NC, Labopin M, Fouillard L, Meloni G, Frassoni F, Iriondo A et al. Retrospective evaluation of autologous bone marrow transplantation vs allogeneic bone marrow transplantation from an HLA identical related donor in acute myelocytic leukemia. A study of the European Cooperative Group for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplantation 1996; 18: 111–117.

    CAS  PubMed  Google Scholar 

  40. Fung HC, Stein A, Slovak M, O'Donnell M R, Snyder DS, Cohen S et al. A long-term follow-up report on allogeneic stem cell transplantation for patients with primary refractory acute myelogenous leukemia: impact of cytogenetic characteristics on transplantation outcome. Biol Blood Marrow Transplant 2003; 9: 766–771.

    CAS  PubMed  Google Scholar 

  41. Burnett AK, Wheatley K, Goldstone AH, Stevens RF, Hann IM, Rees JH et al. The value of allogeneic bone marrow transplant in patients with acute myeloid leukaemia at differing risk of relapse: results of the UK MRC AML 10 trial. Br J Haematol 2002; 118: 385–400.

    PubMed  Google Scholar 

  42. Suciu S, Mandelli F, de Witte T, Zittoun R, Gallo E, Labar B et al. Allogeneic compared with autologous stem cell transplantation in the treatment of patients younger than 46 years with acute myeloid leukemia (AML) in first complete remission (CR1): an intention-to-treat analysis of the EORTC/GIMEMAAML-10 trial. Blood 2003; 102: 1232–1240.

    CAS  PubMed  Google Scholar 

  43. Jourdan E, Boiron JM, Dastugue N, Vey N, Marit G, Rigal-Huguet F et al. Early allogeneic stem-cell transplantation for young adults with acute myeloblastic leukemia in first complete remission: an intent-to-treat long-term analysis of the BGMT experience. J Clin Oncol 2005; 23: 7676–7684.

    PubMed  Google Scholar 

  44. Burnett AK . Current controversies: which patients with acute myeloid leukaemia should receive a bone marrow transplantation?—an adult treater's view. Br J Haematol 2002; 118: 357–364.

    PubMed  Google Scholar 

  45. Harousseau JL, Cahn JY, Pignon B, Witz F, Milpied N, Delain M et al. Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia. The Groupe Ouest Est Leucemies Aigues Myeloblastiques (GOELAM). Blood 1997; 90: 2978–2986.

    CAS  PubMed  Google Scholar 

  46. Dohner K, Schlenk RF, Habdank M, Scholl C, Rucker FG, Corbacioglu A et al. Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood 2005; 106: 3740–3746.

    PubMed  Google Scholar 

  47. Gratwohl A, Hermans J, Goldman JM, Arcese W, Carreras E, Devergie A et al. Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Lancet 1998; 352: 1087–1092.

    CAS  PubMed  Google Scholar 

  48. Sierra J, Storer B, Hansen JA, Martin PJ, Petersdorf EW, Woolfrey A et al. Unrelated donor marrow transplantation for acute myeloid leukemia: an update of the Seattle experience. Bone Marrow Transplantation 2000; 26: 397–404.

    CAS  PubMed  Google Scholar 

  49. Tallman MS, Dewald GW, Gandham S, Logan BR, Keating A, Lazarus HM et al. Impact of cytogenetics on outcome of matched unrelated donor hematopoietic stem cell transplantation for acute myeloid leukemia in first or second complete remission. Blood 2007; 110: 409–417.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Das-Gupta EP, Russell NH, Shaw BE, Pearce RM, Byrne JL . Long-term outcome of unrelated donor transplantation for AML using myeloablative conditioning incorporating pretransplant alemtuzumab. Biol Blood Marrow Transplant 2007; 13: 724–733.

    CAS  PubMed  Google Scholar 

  51. Chantry AD, Snowden JA, Craddock C, Peggs K, Roddie C, Craig JI et al. Long-term outcomes of myeloablation and autologous transplantation of relapsed acute myeloid leukemia in second remission: a British Society of Blood and Marrow Transplantation Registry study. Biol Blood Marrow Transplant 2006; 12: 1310–1317.

    PubMed  Google Scholar 

  52. Lazarus HM, Perez WS, Klein JP, Kollman C, Bate-Boyle B, Bredeson CN et al. Autotransplantation versus HLA-matched unrelated donor transplantation for acute myeloid leukaemia: a retrospective analysis from the Center for International Blood and Marrow Transplant Research. Br J Haematol 2006; 132: 755–769.

    PubMed  Google Scholar 

  53. Meloni G, Diverio D, Vignetti M, Avvisati G, Capria S, Petti MC et al. Autologous bone marrow transplantation for acute promyelocytic leukemia in second remission: prognostic relevance of pretransplant minimal residual disease assessment by reverse-transcription polymerase chain reaction of the PML/RAR alpha fusion gene. Blood 1997; 90: 1321–1325.

    CAS  PubMed  Google Scholar 

  54. Petti MC, Pinazzi MB, Diverio D, Romano A, Petrucci MT, De Santis S et al. Prolonged molecular remission in advanced acute promyelocytic leukaemia after treatment with gemtuzumab ozogamicin (Mylotarg CMA-676). Br J Haematol 2001; 115: 63–65.

    CAS  PubMed  Google Scholar 

  55. Lo-Coco F, Romano A, Mengarelli A, Diverio D, Iori AP, Moleti ML et al. Allogeneic stem cell transplantation for advanced acute promyelocytic leukemia: results in patients treated in second molecular remission or with molecularly persistent disease. Leukemia 2003; 17: 1930–1933.

    CAS  PubMed  Google Scholar 

  56. Biggs JC, Horowitz MM, Gale RP, Ash RC, Atkinson K, Helbig W et al. Bone marrow transplants may cure patients with acute leukemia never achieving remission with chemotherapy. Blood 1992; 80: 1090–1093.

    CAS  PubMed  Google Scholar 

  57. Oyekunle AA, Kroger N, Zabelina T, Ayuk F, Schieder H, Renges H et al. Allogeneic stem-cell transplantation in patients with refractory acute leukemia: a long-term follow-up. Bone Marrow Transplantation 2006; 37: 45–50.

    CAS  PubMed  Google Scholar 

  58. Blaise D, Maraninchi D, Archimbaud E, Reiffers J, Devergie A, Jouet JP et al. Allogeneic bone marrow transplantation for acute myeloid leukemia in first remission: a randomized trial of a busulfan-cytoxan versus cytoxan-total body irradiation as preparative regimen: a report from the Group d'Etudes de la Greffe de Moelle Osseuse. Blood 1992; 79: 2578–2582.

    CAS  PubMed  Google Scholar 

  59. Blaise D, Maraninchi D, Michallet M, Reiffers J, Jouet JP, Milpied N et al. Long-term follow-up of a randomized trial comparing the combination of cyclophosphamide with total body irradiation or busulfan as conditioning regimen for patients receiving HLA-identical marrow grafts for acute myeloblastic leukemia in first complete remission. Blood 2001; 97: 3669–3671.

    CAS  PubMed  Google Scholar 

  60. Clift RA, Buckner CD, Thomas ED, Bensinger WI, Bowden R, Bryant E et al. Marrow transplantation for chronic myeloid leukemia: a randomized study comparing cyclophosphamide and total body irradiation with busulfan and cyclophosphamide. Blood 1994; 84: 2036–2043.

    CAS  PubMed  Google Scholar 

  61. Ringden O, Labopin M, Tura S, Arcese W, Iriondo A, Zittoun R et al. A comparison of busulphan versus total body irradiation combined with cyclophosphamide as conditioning for autograft or allograft bone marrow transplantation in patients with acute leukaemia. Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol 1996; 93: 637–645.

    CAS  PubMed  Google Scholar 

  62. Ringden O, Remberger M, Ruutu T, Nikoskelainen J, Volin L, Vindelov L et al. Increased risk of chronic graft-versus-host disease, obstructive bronchiolitis, and alopecia with busulfan versus total body irradiation: long-term results of a randomized trial in allogeneic marrow recipients with leukemia. Nordic Bone Marrow Transplantation Group. Blood 1999; 93: 2196–2201.

    CAS  PubMed  Google Scholar 

  63. Ringden O, Ruutu T, Remberger M, Nikoskelainen J, Volin L, Vindelov L et al. A randomized trial comparing busulfan with total body irradiation as conditioning in allogeneic marrow transplant recipients with leukemia: a report from the Nordic Bone Marrow Transplantation Group. Blood 1994; 83: 2723–2730.

    CAS  PubMed  Google Scholar 

  64. Socie G, Clift RA, Blaise D, Devergie A, Ringden O, Martin PJ et al. Busulfan plus cyclophosphamide compared with total-body irradiation plus cyclophosphamide before marrow transplantation for myeloid leukemia: long-term follow-up of 4 randomized studies. Blood 2001; 98: 3569–3574.

    CAS  PubMed  Google Scholar 

  65. Ljungman P, Hassan M, Bekassy AN, Ringden O, Oberg G . High busulfan concentrations are associated with increased transplant-related mortality in allogeneic bone marrow transplant patients. Bone Marrow Transplantation 1997; 20: 909–913.

    CAS  PubMed  Google Scholar 

  66. Slattery JT, Clift RA, Buckner CD, Radich J, Storer B, Bensinger WI et al. Marrow transplantation for chronic myeloid leukemia: the influence of plasma busulfan levels on the outcome of transplantation. Blood 1997; 89: 3055–3060.

    CAS  PubMed  Google Scholar 

  67. Deeg HJ, Storer B, Slattery JT, Anasetti C, Doney KC, Hansen JA et al. Conditioning with targeted busulfan and cyclophosphamide for hemopoietic stem cell transplantation from related and unrelated donors in patients with myelodysplastic syndrome. Blood 2002; 100: 1201–1207.

    CAS  PubMed  Google Scholar 

  68. Madden T, de Lima M, Thapar N, Nguyen J, Roberson S, Couriel D et al. Pharmacokinetics of once-daily IV busulfan as part of pretransplantation preparative regimens: a comparison with an every 6-hour dosing schedule. Biol Blood Marrow Transplant 2007; 13: 56–64.

    CAS  PubMed  Google Scholar 

  69. Bornhauser M, Storer B, Slattery JT, Appelbaum FR, Deeg HJ, Hansen J et al. Conditioning with fludarabine and targeted busulfan for transplantation of allogeneic hematopoietic stem cells. Blood 2003; 102: 820–826.

    PubMed  Google Scholar 

  70. Chang C, Storer BE, Scott BL, Bryant EM, Shulman HM, Flowers ME et al. Hematopoietic cell transplantation in patients with myelodysplastic syndrome or acute myeloid leukemia arising from myelodysplastic syndrome: similar outcomes in patients with de novo disease and disease following prior therapy or antecedent hematologic disorders. Blood 2007; 110: 1379–1387.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Bensinger WI, Martin PJ, Storer B, Clift R, Forman SJ, Negrin R et al. Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. N Engl J Med 2001; 344: 175–181.

    CAS  PubMed  Google Scholar 

  72. Eapen M, Horowitz MM, Klein JP, Champlin RE, Loberiza Jr FR, Ringden O et al. Higher mortality after allogeneic peripheral-blood transplantation compared with bone marrow in children and adolescents: the Histocompatibility and Alternate Stem Cell Source Working Committee of the International Bone Marrow Transplant Registry. J Clin Oncol 2004; 22: 4872–4880.

    PubMed  Google Scholar 

  73. Bahceci E, Read EJ, Leitman S, Childs R, Dunbar C, Young NS et al. CD34+ cell dose predicts relapse and survival after T-cell-depleted HLA-identical haematopoietic stem cell transplantation (HSCT) for haematological malignancies. Br J Haematol 2000; 108: 408–414.

    CAS  PubMed  Google Scholar 

  74. Nakamura R, Bahceci E, Read EJ, Leitman SF, Carter CS, Childs R et al. Transplant dose of CD34(+) and CD3(+) cells predicts outcome in patients with haematological malignancies undergoing T cell-depleted peripheral blood stem cell transplants with delayed donor lymphocyte add-back. Br J Haematol 2001; 115: 95–104.

    CAS  PubMed  Google Scholar 

  75. de Lavallade H, Faucher C, Furst S, El-Cheikh J, Vey N, Coso D et al. Allogeneic stem cell transplantation after reduced-intensity conditioning in a patient with T-cell prolymphocytic leukemia: graft-versus-tumor effect and long-term remission. Bone Marrow Transplantation 2006; 37: 709–710.

    CAS  PubMed  Google Scholar 

  76. Grigg AP, Gibson J, Bardy PG, Reynolds J, Shuttleworth P, Koelmeyer RL et al. A prospective multicenter trial of peripheral blood stem cell sibling allografts for acute myeloid leukemia in first complete remission using fludarabine-cyclophosphamide reduced intensity conditioning. Biol Blood Marrow Transplant 2007; 13: 560–567.

    CAS  PubMed  Google Scholar 

  77. Ho AY, Pagliuca A, Kenyon M, Parker JE, Mijovic A, Devereux S et al. Reduced-intensity allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome and acute myeloid leukemia with multilineage dysplasia using fludarabine, busulphan, and alemtuzumab (FBC) conditioning. Blood 2004; 104: 1616–1623.

    CAS  PubMed  Google Scholar 

  78. Mohty M, de Lavallade H, Ladaique P, Faucher C, Vey N, Coso D et al. The role of reduced intensity conditioning allogeneic stem cell transplantation in patients with acute myeloid leukemia: a donor vs no donor comparison. Leukemia 2005; 19: 916–920.

    CAS  PubMed  Google Scholar 

  79. Taussig DC, Davies AJ, Cavenagh JD, Oakervee H, Syndercombe-Court D, Kelsey S et al. Durable remissions of myelodysplastic syndrome and acute myeloid leukemia after reduced-intensity allografting. J Clin Oncol 2003; 21: 3060–3065.

    CAS  PubMed  Google Scholar 

  80. van Besien K, Artz A, Smith S, Cao D, Rich S, Godley L et al. Fludarabine, melphalan, and alemtuzumab conditioning in adults with standard-risk advanced acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol 2005; 23: 5728–5738.

    CAS  PubMed  Google Scholar 

  81. Wong R, Giralt SA, Martin T, Couriel DR, Anagnostopoulos A, Hosing C et al. Reduced-intensity conditioning for unrelated donor hematopoietic stem cell transplantation as treatment for myeloid malignancies in patients older than 55 years. Blood 2003; 102: 3052–3059.

    CAS  PubMed  Google Scholar 

  82. Kottaridis PD, Milligan DW, Chopra R, Chakraverty RK, Chakrabarti S, Robinson S et al. In vivo CAMPATH-1H prevents GvHD following nonmyeloablative stem-cell transplantation. Cytotherapy 2001; 3: 197–201.

    CAS  PubMed  Google Scholar 

  83. Mohty M, Bay JO, Faucher C, Choufi B, Bilger K, Tournilhac O et al. Graft-versus-host disease following allogeneic transplantation from HLA-identical sibling with antithymocyte globulin-based reduced-intensity preparative regimen. Blood 2003; 102: 470–476.

    CAS  PubMed  Google Scholar 

  84. Mohty M, Jacot W, Faucher C, Bay JO, Zandotti C, Collet L et al. Infectious complications following allogeneic HLA-identical sibling transplantation with antithymocyte globulin-based reduced intensity preparative regimen. Leukemia 2003; 17: 2168–2177.

    CAS  PubMed  Google Scholar 

  85. Perez-Simon JA, Kottaridis PD, Martino R, Craddock C, Caballero D, Chopra R et al. Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders. Blood 2002; 100: 3121–3127.

    CAS  PubMed  Google Scholar 

  86. de Lima M, Couriel D, Thall PF, Wang X, Madden T, Jones R et al. Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS. Blood 2004; 104: 857–864.

    CAS  PubMed  Google Scholar 

  87. Matthews DC, Martin PJ, Nourigat C, Appelbaum FR, Fisher DR, Bernstein ID . Marrow ablative and immunosuppressive effects of 131I-anti-CD45 antibody in congenic and H2-mismatched murine transplant models. Blood 1999; 93: 737–745.

    CAS  PubMed  Google Scholar 

  88. Dominietto A, Pozzi S, Miglino M, Albarracin F, Piaggio G, Bertolotti F et al. Donor lymphocyte infusions for the treatment of minimal residual disease in acute leukemia. Blood 2007; 109: 5063–5064.

    CAS  PubMed  Google Scholar 

  89. Dey BR, McAfee S, Colby C, Sackstein R, Saidman S, Tarbell N et al. Impact of prophylactic donor leukocyte infusions on mixed chimerism, graft-versus-host disease, and antitumor response in patients with advanced hematologic malignancies treated with nonmyeloablative conditioning and allogeneic bone marrow transplantation. Biol Blood Marrow Transplant 2003; 9: 320–329.

    PubMed  Google Scholar 

  90. Ogawa H, Tamaki H, Ikegame K, Soma T, Kawakami M, Tsuboi A et al. The usefulness of monitoring WT1 gene transcripts for the prediction and management of relapse following allogeneic stem cell transplantation in acute type leukemia. Blood 2003; 101: 1698–1704.

    CAS  PubMed  Google Scholar 

  91. Miller JS, Weisdorf DJ, Burns LJ, Slungaard A, Wagner JE, Verneris MR et al. Lymphodepletion followed by donor lymphocyte infusion (DLI) causes significantly more acute graft-versus-host disease than DLI alone. Blood 2007; 110: 2761–2763.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Marks DI, Lush R, Cavenagh J, Milligan DW, Schey S, Parker A et al. The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation. Blood 2002; 100: 3108–3114.

    CAS  PubMed  Google Scholar 

  93. Olavarria E, Siddique S, Griffiths MJ, Avery S, Byrne JL, Piper KP et al. Posttransplantation imatinib as a strategy to postpone the requirement for immunotherapy in patients undergoing reduced-intensity allografts for chronic myeloid leukemia. Blood 2007; 110: 4614–4617.

    CAS  PubMed  Google Scholar 

  94. Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, Miller JS, Wagner JE . Rapid and complete donor chimerism in adult recipients of unrelated donor umbilical cord blood transplantation after reduced-intensity conditioning. Blood 2003; 102: 1915–1919.

    CAS  PubMed  Google Scholar 

  95. Schmid C, Schleuning M, Ledderose G, Tischer J, Kolb HJ . Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol 2005; 23: 5675–5687.

    PubMed  Google Scholar 

  96. Schmid C, Schleuning M, Schwerdtfeger R, Hertenstein B, Mischak-Weissinger E, Bunjes D et al. Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation. Blood 2006; 108: 1092–1099.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from Leukaemia Research and CRUK.

Author information

Authors and Affiliations

  1. Centre for Clinical Haematology, University Hospital Birmingham NHS Trust, Birmingham, UK

    C F Craddock

  2. Institute of Cancer Studies, University of Birmingham, Birmingham, UK

    C F Craddock

Authors
  1. C F Craddock
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C F Craddock.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Craddock, C. Full-intensity and reduced-intensity allogeneic stem cell transplantation in AML. Bone Marrow Transplant 41, 415–423 (2008). https://doi.org/10.1038/sj.bmt.1705975

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705975

Keywords

This article is cited by

Search

Advanced search

Quick links