Seminars in Hematology
Volume 44, Issue 4 , Pages 259-266 , October 2007

Acute Myeloid Leukemia and the Position of Autologous Stem Cell Transplantation

  • Dimitri A. Breems

      Affiliations

    • Department of Hematology, Hospital Network Antwerp, General Hospital Stuivenberg, Antwerp, Belgium.
    • ,
  • Bob Löwenberg

      Affiliations

    • Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
    • Corresponding Author InformationAddress correspondence to Bob Löwenberg, MD, PhD, Erasmus University Medical Center, Department of Hematology, PO Box 2040, 3000 CA Rotterdam, The Netherlands.

References 

  1. Löwenberg B, Downing JR, Burnett A. Acute myeloid leukemia. N Engl J Med. 1999;341:1051–1062
  2. Burnett AK. Acute myeloid leukemia: Treatment of adults under 60 years. Rev Clin Exp Hematol. 2002;6:26–45
  3. Wheatley K, Burnett AK, Goldstone AH, Gray RG, Hann IM, Harrison CJ, et al. A simple, robust, validated and highly predictive index for the determination of risk-directed therapy in acute myeloid leukaemia derived form the MRC AML 10 trial. Br J Haematol. 1999;107:69–79
  4. Mrozek K, Marcucci G, Paschka P, Whitman SP, Bloomfield CD. Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: Are we ready for a prognostically prioritized molecular classification?. Blood. 2007;109:431–448
  5. Brenner MK, Rill DR, Moen RC, Krance RA, Mirro J, Anderson WF, et al. Gene-marking to trace origin of relapse after autologous bone marrow transplantation. Lancet. 1993;341:85–86
  6. Burnett AK, Tansey P, Watkins R, Alcorn M, Maharaj D, Singer CR, et al. Transplantation of unpurged autologous bone-marrow in acute myeloid leukaemia in first remission. Lancet. 1984;2:1068–1070
  7. Löwenberg B, Abels J, Van Bekkum DW, Dzoljic G, Hagenbeek A, Hendriks WDH, et al. Transplantation of non-purified autologous bone marrow in patients with AML in first remission. Cancer. 1984;54:2840–2843
  8. Löwenberg B, Verdonck LJ, Dekker AW, Willemze R, Zwaan FE, De Planque M, et al. Autologous bone marrow transplantation in acute myeloid leukemia in first remission: Results of a Dutch prospective study. J Clin Oncol. 1990;8:287–294
  9. Gorin NC, Labopin M, Meloni G, Korbling M, Carella A, Herve P, et al. Autologous bone marrow transplantation for acute myeloblastic leukemia in Europe: Further evidence of the role of marrow purging by mafosfamide (European Cooperative Group for Bone Marrow Transplantation (EBMT)). Leukemia. 1991;5:896–904
  10. Gorin NC. Autologous stem cell transplantation for adult acute leukemia. Curr Opin Oncol. 2002;14:152–159
  11. Wheatley K. Current controversies: Which patients with acute myeloid leukaemia should receive a bone marrow transplantation? (A statistician’s view). Br J Haematol. 2002;118:351–356
  12. Reiffers J, Gaspard MH, Maraninchi D, Michallet M, Marit G, Stoppa AM, et al. Comparison of allogeneic or autologous bone marrow transplantation and chemotherapy in patients with acute myeloid leukaemia in first remission: A prospective controlled trail. Br J Haematol. 1989;72:57–63
  13. Zittoun RA, Mandelli F, Willemze R, De Witte T, Labar B, Resegotti L, et al. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. N Engl J Med. 1995;332:217–223
  14. Reiffers J, Stoppa AM, Attal M, Michallet M, Marit G, Blaise D, et al. Allogeneic vs autologous stem cell transplantation vs chemotherapy in patients with acute myeloid leukemia in first remission: The BGMT 87 study. Leukemia. 1996;10:1782–1874
  15. 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. Blood. 1997;90:2978–2986
  16. Cassileth PA, Harrington DP, Appelbaum FR, Lazarus HM, Rowe JM, Paietta E, et al. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med. 1998;339:1649–1656
  17. Burnett AK, Goldstone AH, Stevens RMF, Hann IM, Rees JKH, Gray RG, et al. Randomised comparison of addition of autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission: Results of MRC AML 10 trial. Lancet. 1998;351:700–708
  18. Breems DA, Boogaerts MA, Dekker AW, Van Putten WLJ, Sonneveld P, Huijgens PC, et al. Autologous bone marrow transplantation as consolidation therapy in the treatment of adult patients under 60 years with acute myeloid leukaemia in first complete remission: A prospective randomized Dutch-Belgian Haemato-Oncology Co-operative group (HOVON) and Swiss Group for Clinical Cancer Research (SAKK) trial. Br J Haematol. 2005;128:59–65
  19. Tsimberidou AM, Stavroyianni N, Viniou N, Papioannou M, Tiniakou M, Marinakis T, et al. Comparison of allogeneic stem cell transplantation, high-dose cytarabine, and autologous peripheral stem cell transplantation as postremission treatment in patients with de novo acute myelogenous leukemia. Cancer. 2003;97:1721–1731
  20. Büchner T, Berdel WE, Schoch C, Haferlach T, Serve HL, Kienast J, et al. Double induction containing either two courses or one course of high-dose cytarabine plus mitoxantrone and postremission therapy by either autologous stem-cell transplantation or by prolonged maintenance for acute myeloid leukemia. J Clin Oncol. 2006;24:2480–2489
  21. Tallman MS, Pérez WS, Lazarus HM, Gale RP, Maziarz RT, Rowe JM, et al. Pretransplantation consolidation chemotherapy decreases leukemia relapse after autologous blood and bone marrow transplants for acute myelogenous leukemia in first remission. Biol Blood Marrow Transplant. 2006;12:204–216
  22. Nathan PC, Sung L, Crump M, Beyene J. Consolidation therapy with autologous bone marrow transplantation in adults with acute myeloid leukemia: A meta-analysis. J Natl Cancer Inst. 2004;96:38–45
  23. Levi I, Grotto I, Yerushalmi R, Ben-Bassat I, Shpilberg O. Meta-analysis of autologous bone marrow transplantation versus chemotherapy in adult patients with acute myeloid leukemia in first remission. Leuk Res. 2004;28:605–612
  24. Breems DA, Van Putten WLJ, Huijgens PC, Ossenkoppele GJ, Verhoef GEG, Verdonck LF, et al. Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Clin Oncol. 2005;23:1969–1978
  25. Mitus AJ, Miller KB, Schenkein DP, Ryan HF, Parsons SK, Wheeler C, et al. Improved survival for patients with acute myelogenous leukemia. J Clin Oncol. 1995;13:560–569
  26. Keating S, De Witte T, Suciu S, Willemze R, Hayat M, Labar B, et al. The influence of HLA-matched sibling donor availability on treatment outcome for patients with AML: An analysis of the AML 8A study of the EORTC Leukaemia Cooperative Group and GIMEMA. Br J Haematol. 1998;102:1344–1353
  27. 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/GIMEMA AML-10 trial. Blood. 2003;102:1232–1240
  28. Sierra J, Brunet S, Granena A, Olive T, Bueno J, Ribera JM, et al. Feasibility and results of bone marrow transplantation after remission induction and intensification chemotherapy in de novo acute myeloid leukemia. J Clin Oncol. 1996;14:1353–1363
  29. Burnett AK, Hills RK, Goldstone AH, Milligan D, Prentice AG, Hann I, et al. The impact of transplant in AML in 2nd CR: A prospective study of 741 in the MRC AML 10 and 12 trials. Blood. 2004;104:179a;(abstr)
  30. Cornelissen J, van Putten W, 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
  31. Gratwohl A, Baldomero H, Frauendorfer K, Urbano-Ispizua A Joint Accreditation Committee International Society for Cellular Therapy European Group for Blood and Marrow Transplantation. EBMT activity survey 2004 and changes in disease indication over the past 15 years. Bone Marrow Transplant. 2006;37:1069–1085
  32. Lazarus HM, Pérez 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
  33. Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, et al. The importance of diagnostic cytogenetics on outcome in AML: Analysis of 1,612 patients entered in the MRC AML 10 trial. Blood. 1998;92:2322–2333
  34. Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukaemia: A Southwest Oncology Group/Eastern Cooperative Group study. Blood. 2000;96:4075–4083
  35. Byrd JC, Mrozek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC, et al. Pretreatment cytogenetics abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: Results from Cancer and Leukemia Group B (CALGB 8461). Blood. 2002;100:4325–4336
  36. Tallman MS, Andersen JW, Schiffer CA, Appelbaum RF, Feusner JH, Goods WG, et al. All-trans retinoic acid in acute promyelocytic leukemia: Long term outcome and prognostic factor analysis from the North American Intergroup protocol. Blood. 2002;100:4298–4302
  37. Sanz MA, Martin G, Gonzalez M, Leon A, Rayon C, Rivas C, et al Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: A multicenter study by the PETHEMA group. Blood. 2004;103:1237–1243
  38. Meloni G, Diverio D, Vignetti M, Avvisati G, Capria S, Concetta Petti M, 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/RARα fusion gene. Blood. 1997;90:1321–1325
  39. De Botton S, Fawaz A, Chevret S, Dombret H, Thomas X, Sanz M, et al. Autologous and allogeneic stem-cell transplantation as salvage treatment of acute promyelocytic leukemia initially treated with all-trans-retinoic acid: A retrospective analysis of the European Acute Promyelocytic Leukemia Group. J Clin Oncol. 2005;23:120–126
  40. Bloomfield CD, Lawrence D, Byrd JC, Carroll A, Pettenatie MJ, Tantravahi R, et al. Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetics subtype. Cancer Res. 1998;58:4173–4179
  41. Byrd JC, Dodge RK, Carroll A, Baer MR, Edwards C, Stamberg J, et al. Patients with t(8;21)(q22;q22) and acute myeloid leukemia have superior failure-free and overall survival when repetitive cycles of high-dose cytarabine are administered. J Clin Oncol. 1999;17:3767–3775
  42. Byrd JC, Ruppert AS, Mrozek K, Carroll AJ, Edwards CG, Arthur DC, et al. Repetitive cycles of high-dose cytarabine benefit patients with acute myeloid leukemia and inv(16)(p13;q22) or t(16;16)(p13;q22): Results from CALGB 8461. J Clin Oncol. 2004;22:1087–1094
  43. Schlenk RF, Benner A, Krauter J, Buchner T, Sauerland C, Ehninger G, et al. Individual patient data-based meta-analysis of patients aged 16 to 60 years with core binding factor acute myeloid leukemia: A survey of the German Acute Myeloid Leukemia Intergroup. J Clin Oncol. 2004;22:32741–33750
  44. Farag SS, Ruppert AS, Mrozek K, Mayer RJ, Stone RM, Carroll AJ. Outcome of induction and postremission therapy in younger adults with acute myeloid leukaemia with normal karyotype: A Cancer and Leukemia Group B study. J Clin Oncol. 2005;23:482–493
  45. Burnett AK, Wheatley K, Goldstone AH, Stevens SF, Hann IM, Rees JHK, 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
  46. Kiyoi H, Naoe T, Nakano Y, Yokota S, Minami S, Miyawaki S, et al. Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukaemia. Blood. 1999;93:3074–3080
  47. Abu-Duhier FM, Goodeve AC, Wilson GA, Gari MA, Peake IR, Rees DC, et al. FLT3 internal tandem duplication mutations in adult acute myeloid leukaemia define a high-risk group. Br J Haematol. 2000;111:190–195
  48. Rombouts WJ, Blokland I, Löwenberg B, Ploemacher RE. Biological characteristics and prognosis of adult acute myeloid leukemia with internal tandem duplications in the Flt3 gene. Leukemia. 2000;14:675–683
  49. Kottaridis PD, Gale RE, Frew ME, Harrison G, Langabeer SE, Belton AA, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: Analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 2001;98:1752–1759
  50. Whitman SP, Archer KJ, Feng L, Baldus C, Becknell B, Carlson BD, et al. Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukaemia with normal cytogenetics and the internal tandem duplication of FLT3: A Cancer and Leukemia Group B study. Cancer Res. 2001;61:7233–7239
  51. Gale RE, Hills R, Kottaridis PD, Srirangan S, Wheatley K, Burnett AK, et al. No evidence that FLT3 status should be considered as an indicator for transplantation in acute myeloid leukemia (AML): An analysis of 1135 patients, excluding acute promyelocytic leukemia, from the UK MRC AML 10 and 12 trials. Blood. 2005;106:3658–3665
  52. Palmieri S, Ferrara F, Leoni F, Ciolli S, Pollio F, D’Amico MR, et al. Myeloablative chemotherapy followed by autologous stem cell infusion may overcome the adverse prognostic impact of FLT3 (foetal liver tyrosine kinase 3) mutations in patients with acute myeloid leukaemiq and normal karyotype. Hematol Oncol. 2007;25:1–5
  53. Bornhäuser M, Illmer T, Schaich M, Soucek S, Ehninger G, Thiede C. Improved outcome after stem-cell transplantation in FLT3/ITD-positive AML. Blood. 2007;109:2264–2265(letter)
  54. Gale RE, Hills R, Wheatley K, Burnett AK, Linch DC. Still a need for more robust evidence that FLT3/ITD status should influence the decision to proceed to transplantation in AML patients. Blood. 2007;109:2265;(letter)
  55. Löwenberg B. Managing therapy in older adult patients with acute myeloid leukemia. Semin Hematol. 2001;38:10–16
  56. Sekeres MA, Stone AM. The challenge of acute myeloid leukemia in older patients. Curr Opin Oncol. 2002;14:24–30
  57. Archimbaud E, Jehn U, Thomas X, De Cataldo F, Fillet G, Belhabri A, et al. Multicenter randomised phase II trial of idarubicin vs mitxantrone, combined with VP-16 and cytarabine for induction/consolidation therapy, followed by a feasibility study of autologous peripheral blood stem cell transplantation in elderly patients with acute myeloid leukemia. Leukemia. 1999;13:843–849
  58. Montillo M, Tedeschi A, Pagano L, Venditti A, Ferrara F, Fabris P, et al. Feasibility of peripheral blood stem cell rescue as intensification in elderly patients with acute myelocytic leukaemia: A pilot study from the Gimema Group. Br J Haematol. 2000;111:334–337
  59. Oriol A, Ribera JM, Esteve J, Guardia R, Brunet S, Bueno J, et al. Feasibility and results of autologous stem cell transplantation in de novo acute myeloid leukaemia in patients over 60 years old (Results of the CETLAM AML-99 protocol). Haematologica. 2004;89:791–800
  60. Ferrara F, Palmieri S, Celentano M, De Simone M, Pollio F, D’Amico MR, et al. Feasibility of autologous peripheral blood stem cell transplantation in elderly patients with acute myeloid leukemia. Leuk Lymphoma. 2006;47:1593–1598
  61. Herr AL, Labopin M, Blaise D, Milpied N, Potter M, Michallet M, et al. HLA-identical sibling allogeneic peripheral blood stem cell transplantation with reduced intensity conditioning compared to autologous peripheral blood stem cell transplantation for elderly patients with de novo acute myeloid leukemia. Leukemia. 2007;21:129–135
  62. 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 leukaemia (A study of the European Cooperative Group for Blood and Marrow Transplantation (EBMT)). Bone Marrow Transplant. 1996;18:111–117
  63. Chantry AD, Snowden JA, Craddock C, Peggs K, Roddie C, Craig JIO, 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 Translant. 2006;12:1310–1317
  64. Ringdén O, Labopin M, Gorin NC, Meloni G, Blaise D, Reiffers J, et al. The dismal outcome in patients with acute leukaemia who relapse after an autograft is improved if a second autograft or a matched allograft is performed. Bone Marrow Transplant. 2000;25:1053–1058
  65. Demirer T, Buckner CD, Appelbaum FR, Petersen FB, Rowley S, Weaver CH, et al. Rapid engraftment after autologous transplantation utilizing marrow and recombinant granulocyte colony-stimulating factor-mobilized peripheral blood stem cells in patients with acute myelogenous leukemia. Bone Marrow Transplant. 1995;15:915–922
  66. Demirer T, Petersen FB, Bensinger WI, Appelbaum FR, Fefer A, Rowley S, et al. Autologous transplantation with peripheral blood stem cells collected after granulocyte colony-stimulating factor in patients with acute myelogenous leukemia. Bone Marrow Transplant. 1996;18:29–34
  67. Vellenga E, Van Putten WLJ, Boogaerts MA, Daenen SMGJ, Verhoef GEG, Hagenbeek A, et al. Peripheral blood stem cell transplantation as an alternative to autologous marrow transplantation in the treatment of acute myeloid leukemia?. Bone Marrow Transplant. 1999;23:1279–1282
  68. Reiffers J, Labopin M, Sanz M, Korbling M, Blaise D, De la Rubia J, et al. Autologous blood cell vs marrow transplantation for acute myeloid leukemia in complete remission: An EBMT retrospective analysis. Bone Marrow Transplant. 2000;25:1115–1119
  69. De Witte TM, Keating S, Suciu S, Zittoun R, Mandelli F, Amadori S, et al. The value of autologous PSCT versus autologous BMT for patients with AML in first CR and impact of mobilized numbers CD34-cells on outcome: Final results of the randomized AML-10 trial of the EORTC LG and GIMEMA. Blood. 2003;102:739a;(abstr)
  70. Keating S, Suciu S, De Witte T, Zittoun R, Mandelli F, Belhabri A, et al. The stem cell mobilizing capacity of patients with acute myeloid leukemia in complete remission correlates with relapse risk: Results of the EORTC-GIMEMA AML-10 trial. Leukemia. 2003;17:60–67
  71. Feller N, Schuurhuis GJ, Van der Pol MA, Westra G, Weijers GWD, Van Stijn A, et al. High percentage of CD34-positive cells in autologous AML peripheral blood stem cell products reflects inadequate in vivo purging and low chemotherapeutic toxicity in a subgroup of patients with poor clinical outcome. Leukemia. 2003;17:68–75
  72. Löwenberg B, Van Putten W, Theobald M, Gmür J, Verdonck L, Sonneveld P, et al. Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia. N Engl J Med. 2003;349:743–752

PII: S0037-1963(07)00119-9

doi: 10.1053/j.seminhematol.2007.08.002

Seminars in Hematology
Volume 44, Issue 4 , Pages 259-266 , October 2007

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