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.

  • Original Article
  • Published:

Acute Myeloid Leukaemia

Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia: disease status by marrow blasts is the strongest prognostic factor

Bone Marrow Transplantation volume 31, pages 1089–1095 (2003)Cite this article

Summary:

We analyzed predictive factors for the outcome of 113 acute myeloid leukemia patients receiving reduced-intensity conditioning prior to allogeneic hematopoietic stem cell transplantation (HSCT). Patients were ineligible for conventional-intensity HSCT. Conditioning consisted of fludarabine and 50% of the conventional dose of busulfan (n=93) or total body irradiation (n=20). The source of stem cells was blood in 102 patients, marrow in 10, and both in one. In total, 50 (44.2%) donors were HLA-matched siblings, 50 (44.2%) unrelated fully matched and 13 (11.5%) partially mismatched family (n=1) or unrelated (n=12) donors. In all, 107 (94.6%) patients showed neutrophil and platelet engraftment after a median time of 13.5 and 13 days. The probabilities of event-free survival (EFS) (median follow-up: 12 months) were 49% for patients with less than 5% blasts in the marrow, 24% for patients with 5–20% blasts (P=0.002) and 14% with >20% blasts (P⩽0.001). Death occurred because of relapse in 29 patients (25.6%), infection in 12 patients (10.6%), acute graft-versus-host disease in eight patients (7.0%) and organ toxicity in nine patients (7.9%). In multivariate analysis, higher number of blasts in the marrow, alternative donors and low Karnofsky performance score were independent adverse prognostic factors for EFS.

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Wiernik PH, Banks PLC, Case Jr DC et al. Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood 1992; 79: 313–319.

    CAS  PubMed  Google Scholar 

  2. Bishop JF, Matthews JP, Young GA et al. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood 1996; 87: 1710–1717.

    CAS  PubMed  Google Scholar 

  3. 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 

  4. Frassoni F, Labopin M, Gluckman E et al. Results of allogeneic bone marrow transplantation for acute leukaemia have improved over time in Europe. Bone Marrow Transplant 1996; 17: 13–18.

    CAS  PubMed  Google Scholar 

  5. Cift R, Buckner C, Appelbaum F et al. Allogeneic marrow transplantation in patients with acute myeloid leukemia in first remission: a randomized trial of two irradiation regimens. Blood 1990; 76: 1867–1871.

    Google Scholar 

  6. Auer I, Gale R . Are new conditioning regimens for transplantation in acute myelogenous leukemia better? Bone Marrow Transplant 1991; 4: 255–262.

    Google Scholar 

  7. Yin JA, Johnson PRE . Clinical annotation. Acute myeloid leukaemia in the elderly: biology and treatment. Br J Haematol 1993; 83: 1–6.

    Article  Google Scholar 

  8. Weiden P, Flournoy N, Thomas E 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  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  10. McSweeney PA, Niederwieser D, Shizuru JA et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 2001; 97: 3390–3400.

    Article  CAS  PubMed  Google Scholar 

  11. Giralt S, Estey E, Albitar M et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood 1997; 89: 4531–4536.

    CAS  PubMed  Google Scholar 

  12. Corradini P, Tarella C, Olivieri A et al. Reduced-intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies. Blood 2002; 99: 75–82.

    Article  CAS  PubMed  Google Scholar 

  13. Giralt S, Thall PF, Khouri I et al. Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. Blood 2001; 97: 631–637.

    Article  CAS  PubMed  Google Scholar 

  14. Slavin S, Nagler A, Naparstek Y et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 1998; 91: 756–763.

    CAS  PubMed  Google Scholar 

  15. Kottaridis DP, Milligan DW, Chopra R et al. In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation. Blood 2000; 96: 2419–2425.

    CAS  PubMed  Google Scholar 

  16. Ottinger HD, Albert E, Arnold R et al. German consensus on immunogenetic donor search for transplantation of allogeneic bone marrow and peripheral blood stem cell. Bone Marrow Transplant 1997; 20: 101–105.

    Article  CAS  PubMed  Google Scholar 

  17. Kaplan E, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–462.

    Article  Google Scholar 

  18. Venditti A, Buccisano F, Del Poeta G et al. Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukaemia. Blood 2000; 96: 3948–3952.

    CAS  PubMed  Google Scholar 

  19. Sierra J, Storer B, Hansen JA et al. Unrelated donor marrow transplantation for acute myeloid leukemia: an update of the Seattle experience. Bone Marrow Transplant 2000; 26: 397–404.

    Article  CAS  PubMed  Google Scholar 

  20. Tallman MS, Rowlings PA, Milone G et al. Effect of postremission chemotherapy before human leukocyte antigen- identical sibling transplantation for acute myelogenous leukemia in first complete remission. Blood 2000; 96: 1254–1258.

    CAS  PubMed  Google Scholar 

  21. 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 

  22. Panse JP, Heimfeld S, Guthrie KA et al. Effect of PBSC graft-composition on T-cell chimerism, rejection and outcome in non-myealoablative HSCT: NK-cells predict for T-cell engraftment. Blood 2001; 98: 477a [Abstr.].

    Google Scholar 

  23. Bornhäuser M, Thiede C, Platzbecker U et al. Dose-reduced conditioning and allogeneic hematopoietic stem cell transplantation from unrelated donors in 42 patients. Clin Cancer Res. 2001; 7: 2254–2262.

    PubMed  Google Scholar 

  24. Socié G, Stone JV, Wingard JR et al. Long-term survival and late deaths after allogeneic bone marrow transplantation. N Engl J Med 1999; 341: 14–21.

    Article  PubMed  Google Scholar 

  25. Maury S, Mary JY, Rabian C et al. Prolonged immune deficiency following allogeneic stem cell transplantation: risk factors and complications in adult patients. Br J Haematol 2001; 115: 630–641.

    Article  CAS  PubMed  Google Scholar 

  26. Michallet M, Bilger K, Garban F et al. Allogeneic hematopoietic stem-cell transplantation after nonmyeloablative preparative regimens: impact of pretransplantation and posttransplantation factors on outcome. J Clin Oncol 2001; 19: 3340–3349.

    Article  CAS  PubMed  Google Scholar 

  27. Martino R, Caballero MD, Peres Simon JA et al. Evidence for a graft-versus-leukemia effect after allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning in acute myelogenous leukemia and myelodysplastic syndromes. Blood 2002; 100: 2243–2245.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank all of the physicians and nursing staff in the participating study centers that have been involved in the care of the patients. This work was supported in part by the Kompetenznetz ‘Akute und Chronische Leukämien’. Parts of the study were presented at the 43rd Annual Meeting of the American Society of Hematology in Orlando Florida, December 2001.

Author information

Authors and Affiliations

  1. Klinik und Poliklinik für Innere Medizin II, Friedrich-Schiller-Universität Jena, Germany

    H G Sayer & K Höffken

  2. Department of Medicine/Hematology and Oncology, Westfälische Wilhelms-Universität Münster, Germany

    M Kröger & J Kienast

  3. Abteilung für Hämatologie, Onkologie und Immunologie, Philipps-Universität Marburg, Germany

    J Beyer

  4. Klinik für Knochenmarktransplantation, Idar-Oberstein, Germany

    M Kiehl & A Fauser

  5. Abteilung für Hämatologie, Innere Medizin, J.-W. Goethe Universität Frankfurt, Germany

    S A Klein & H Martin

  6. Medizinische Klinik Nürnberg, Germany

    K Schaefer-Eckart

  7. Deutsche Klinik für Diagnostik - Knochenmarktransplantation Wiesbaden, Germany

    R Schwerdtfeger

  8. Medizinische Klinik II m. S. Hämatologie und Onkologie, Champus Charite-Mitte, Humboldt Universität Berlin, Germany

    W Siegert & J Schetelig

  9. Klinik für Knochenmarktransplantation, Universität Essen, Germany

    V Runde & D W Beelen

  10. Medizinische Klinik und Poliklinik I, Carl Gustav Carus Universität Dresden, Germany

    C Theuser, G Ehninger & M Bornhäuser

Authors
  1. H G Sayer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Kröger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Beyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Kiehl
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S A Klein
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K Schaefer-Eckart
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. R Schwerdtfeger
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. W Siegert
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. V Runde
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. C Theuser
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. H Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. J Schetelig
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. D W Beelen
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. A Fauser
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. J Kienast
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. K Höffken
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. G Ehninger
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. M Bornhäuser
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the Cooperative German Transplant Study Group (CGTG)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sayer, H., Kröger, M., Beyer, J. et al. Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia: disease status by marrow blasts is the strongest prognostic factor. Bone Marrow Transplant 31, 1089–1095 (2003). https://doi.org/10.1038/sj.bmt.1704062

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704062

Keywords

This article is cited by

Search

Advanced search

Quick links