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:

Is it appropriate to offer allogeneic hematopoietic stem cell transplantation to patients with primary refractory acute myeloid leukemia?

Bone Marrow Transplantation volume 36, pages 183–191 (2005)Cite this article

Summary:

Although continued advances have been made in the treatment of acute myeloid leukemia (AML), approximately 20–30% of patients will never achieve a remission. For these patients with primary refractory AML, the only curative option remains an allogeneic stem cell transplant. Allogeneic transplantation provides the ability to administer myeloablative doses of chemotherapy or chemoradiotherapy, as well as the advantage of a possible graft-versus-leukemia effect. Difficulty in interpreting the literature is due to selection bias, in particular, the varying definitions of primary refractory disease with respect to the morphological criteria and the number of induction regimen required before being defined as being refractory. Regardless, it is a procedure with high treatment-related mortality and risk of relapse. Most studies demonstrate an event-free survival of 10–20% at 5 years. Predictive factors of outcome include blast cell count in the marrow, karyotype, the number of prior regimen, age, performance status and availability of a related donor. These prognostic factors should be considered prior to offering allogeneic transplantation for primary refractory AML. Those patients with many favorable prognostic factors and an HLA-matched related donor available would be the best candidate for the procedure. Those with many poor prognostic factors and only an unrelated donor available may be better served by being offered palliation or being enrolled in investigational studies.

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. Thomas ED, Buckner CD, Banaji M et al. One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation. Blood 1977; 49: 511–533.

    CAS  PubMed  Google Scholar 

  2. Grimwade D, Walker H, Oliver F et al. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties. Blood 1998; 92: 2322–2333.

    CAS  PubMed  Google Scholar 

  3. Slovak ML, Kopecky KJ, Cassileth PA et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood 2000; 96: 4075–4083.

    CAS  PubMed  Google Scholar 

  4. Tallman MS, Andersen JW, Schiffer CA et al. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med 1997; 337: 1021–1028.

    Article  CAS  PubMed  Google Scholar 

  5. Fenaux P, Chastang C, Chevret S et al. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood 1999; 94: 1192–1200.

    CAS  PubMed  Google Scholar 

  6. Soignet SL, Maslak P, Wang ZG et al. Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. N Engl J Med 1998; 339: 1341–1348.

    Article  CAS  PubMed  Google Scholar 

  7. Mayer RJ, Davis RB, Schiffer CA et al. Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. N Engl J Med 1994; 331: 896–903.

    Article  CAS  PubMed  Google Scholar 

  8. Goldstone A, Burnett A, Avivi I et al. Secondary acute myeloid leukaemia has a worse outcome than de novo AML, even taking into account cytogenetics and age. AML 10, 11, 12 MRC trials. Blood 2002; 100: 88a.

    Google Scholar 

  9. Horowitz MM, Gale RP, Sondel PM et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990; 75: 555–562.

    CAS  PubMed  Google Scholar 

  10. Collins Jr RH, Shpilberg O, Drobyski WR et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol 1997; 15: 433–444.

    Article  PubMed  Google Scholar 

  11. Cassileth PA, Harrington DP, Appelbaum FR 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.

    Article  CAS  PubMed  Google Scholar 

  12. Zittoun RA, Mandelli F, Willemze R et al. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto (GIMEMA) Leukemia Cooperative Groups. N Engl J Med 1995; 332: 217–223.

    Article  CAS  PubMed  Google Scholar 

  13. Cheson BD, Cassileth PA, Head DR et al. Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia. J Clin Oncol 1990; 8: 813–819.

    Article  CAS  PubMed  Google Scholar 

  14. Cheson BD, Bennett JM, Kopecky KJ et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 2003; 21: 4642–4649.

    Article  PubMed  Google Scholar 

  15. Wheatley K, Burnett AK, Goldstone AH et al. A simple, robust, validated and highly predictive index for the determination of risk-directed therapy in acute myeloid leukaemia derived from the MRC AML 10 trial. United Kingdom Medical Research Council's Adult and Childhood Leukaemia Working Parties. Br J Haematol 1999; 107: 69–79.

    Article  CAS  PubMed  Google Scholar 

  16. Forman SJ, Schmidt GM, Nademanee AP et al. Allogeneic bone marrow transplantation as therapy for primary induction failure for patients with acute leukemia. J Clin Oncol 1991; 9: 1570–1574.

    Article  CAS  PubMed  Google Scholar 

  17. Biggs JC, Horowitz MM, Gale RP 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 

  18. Mehta J, Powles R, Horton C et al. Bone marrow transplantation for primary refractory acute leukaemia. Bone Marrow Transplant 1994; 14: 415–418.

    CAS  PubMed  Google Scholar 

  19. Grigg AP, Szer J, Beresford J et al. Factors affecting the outcome of allogeneic bone marrow transplantation for adult patients with refractory or relapsed acute leukaemia. Br J Haematol 1999; 107: 409–418.

    Article  CAS  PubMed  Google Scholar 

  20. Michallet M, Thomas X, Vernant JP et al. Long-term outcome after allogeneic hematopoietic stem cell transplantation for advanced stage acute myeloblastic leukemia: a retrospective study of 379 patients reported to the Societe Francaise de Greffe de Moelle (SFGM). Bone Marrow Transplant 2000; 26: 1157–1163.

    Article  CAS  PubMed  Google Scholar 

  21. Fung HC, Stein A, Slovak M 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.

    Article  CAS  PubMed  Google Scholar 

  22. Zander AR, Dicke KA, Keating M et al. Allogeneic bone marrow transplantation for acute leukemia refractory to induction chemotherapy. Cancer 1985; 56: 1374–1379.

    Article  CAS  PubMed  Google Scholar 

  23. Wong R, Shahjahan M, Wang X et al. Prognostic factors for outcomes of patients with refractory or relapsed acute myelogenous leukemia or myelodysplastic syndromes undergoing allogeneic progenitor cell transplantation. Biol Blood Marrow Transplant 2005; 11: 108–114.

    Article  PubMed  Google Scholar 

  24. Esteve J, Labopin M, Finke J et al. Allogeneic stem-cell transplantation for patients with de novo acute myeloid leukemia not in complete response: results of a survey from the European Group for Blood and Bone Marrow Transplantation (EBMT). Blood 2004; 104: 633a.

    Google Scholar 

  25. Petersdorf EW, Anasetti C, Martin PJ, Hansen JA . Tissue typing in support of unrelated hematopoietic cell transplantation. Tissue Antigens 2003; 61: 1–11.

    Article  CAS  PubMed  Google Scholar 

  26. Giebel S, Locatelli F, Lamparelli T et al. Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors. Blood 2003; 102: 814–819.

    Article  CAS  PubMed  Google Scholar 

  27. Cook MA, Milligan DW, Fegan CD et al. The impact of donor KIR and patient HLA-C genotypes on outcome following HLA-identical sibling hematopoietic stem cell transplantation for myeloid leukemia. Blood 2004; 103: 1521–1526.

    Article  CAS  PubMed  Google Scholar 

  28. Bensinger WI, Martin PJ, Storer B 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.

    Article  CAS  PubMed  Google Scholar 

  29. Ringden O, Labopin M, Bacigalupo A et al. Transplantation of peripheral blood stem cells as compared with bone marrow from HLA-identical siblings in adult patients with acute myeloid leukemia and acute lymphoblastic leukemia. J Clin Oncol 2002; 20: 4655–4664.

    Article  CAS  PubMed  Google Scholar 

  30. Russell JA, Tran HT, Quinlan D et al. Once-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes. Biol Blood Marrow Transplant 2002; 8: 468–476.

    Article  CAS  PubMed  Google Scholar 

  31. de Lima M, Couriel D, Thall PF 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.

    Article  CAS  PubMed  Google Scholar 

  32. Giralt S, Bensinger W, Goodman M et al. 166Ho-DOTMP plus melphalan followed by peripheral blood stem cell transplantation in patients with multiple myeloma: results of two phase 1/2 trials. Blood 2003; 102: 2684–2691.

    Article  CAS  PubMed  Google Scholar 

  33. Khouri IF, Saliba RM, Hosing C et al. Concurrent administration of high-dose rituximab before and after autologous stem-cell transplantation for relapsed aggressive B-cell non-Hodgkin's lymphomas. J Clin Oncol 2005; 23: 2240–2247.

    Article  CAS  PubMed  Google Scholar 

  34. Pagel JM, Matthews DC, Appelbaum FR et al. The use of radioimmunoconjugates in stem cell transplantation. Bone Marrow Transplant 2002; 29: 807–816.

    Article  CAS  PubMed  Google Scholar 

  35. Matthews DC, Appelbaum FR, Eary JF et al. Phase I study of (131)I-anti-CD45 antibody plus cyclophosphamide and total body irradiation for advanced acute leukemia and myelodysplastic syndrome. Blood 1999; 94: 1237–1247.

    CAS  PubMed  Google Scholar 

  36. Forero A, Weiden PL, Vose JM et al. Phase 1 trial of a novel anti-CD20 fusion protein in pretargeted radioimmunotherapy for B-cell non-Hodgkin lymphoma. Blood 2004; 104: 227–236.

    Article  CAS  PubMed  Google Scholar 

  37. Abi-Habib RJ, Liu S, Bugge TH et al. A urokinase-activated recombinant diphtheria toxin targeting the granulocyte–macrophage colony-stimulating factor receptor is selectively cytotoxic to human acute myeloid leukemia blasts. Blood 2004; 104: 2143–2148.

    Article  CAS  PubMed  Google Scholar 

  38. Wingard JR, Leather H . A new era of antifungal therapy. Biol Blood Marrow Transplant 2004; 10: 73–90.

    Article  CAS  PubMed  Google Scholar 

  39. Spielberger R, Stiff P, Bensinger W et al. Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med 2004; 351: 2590–2598.

    Article  CAS  PubMed  Google Scholar 

  40. Krijanovski OI, Hill GR, Cooke KR et al. Keratinocyte growth factor separates graft-versus-leukemia effects from graft-versus-host disease. Blood 1999; 94: 825–831.

    CAS  PubMed  Google Scholar 

  41. Reddy P, Maeda Y, Hotary K et al. Histone deacetylase inhibitor suberoylanilide hydroxamic acid reduces acute graft-versus-host disease and preserves graft-versus-leukemia effect. Proc Natl Acad Sci USA 2004; 101: 3921–3926.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Wadleigh M, DeAngelo DJ, Griffin JD, Stone RM . After chronic myelogenous leukemia: tyrosine kinase inhibitors in other hematologic malignancies. Blood 2005; 105: 22–30.

    Article  CAS  PubMed  Google Scholar 

  43. Kantarjian HM, O’Brien S, Cortes JE et al. Imatinib mesylate therapy for relapse after allogeneic stem cell transplantation for chronic myelogenous leukemia. Blood 2002; 100: 1590–1595.

    CAS  PubMed  Google Scholar 

  44. Wassmann B, Pfeifer H, Stadler M et al. Early molecular response to post-transplant imatinib determines outcome in MRD-positive Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL). Blood 2005 (prepublished online).

  45. Anderson Jr LD, Savary CA, Mullen CA . Immunization of allogeneic bone marrow transplant recipients with tumor cell vaccines enhances graft-versus-tumor activity without exacerbating graft-versus-host disease. Blood 2000; 95: 2426–2433.

    CAS  PubMed  Google Scholar 

  46. Chen BJ, Cui X, Liu C, Chao NJ . Prevention of graft-versus-host disease while preserving graft-versus-leukemia effect after selective depletion of host-reactive T cells by photodynamic cell purging process. Blood 2002; 99: 3083–3088.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Leukemia/Bone Marrow Transplantation Program of British Columbia, Vancouver Hospital and Health Sciences Center, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada

    K W Song

  2. Leukemia and Allogeneic Stem Cell Transplant Services, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Canada

    J Lipton

Authors
  1. K W Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J Lipton
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K W Song.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Song, K., Lipton, J. Is it appropriate to offer allogeneic hematopoietic stem cell transplantation to patients with primary refractory acute myeloid leukemia?. Bone Marrow Transplant 36, 183–191 (2005). https://doi.org/10.1038/sj.bmt.1705038

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705038

Keywords

This article is cited by

Search

Advanced search

Quick links