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:

Unrelated Donor Transplants

Unrelated donor marrow transplantation for acute myeloid leukemia: an update of the Seattle experience

Abstract

Between 1985 and 1998, 161 patients with primary acute myeloid leukemia (AML) received T-replete bone marrow transplantation (BMT) from unrelated donors in Seattle. Median age was 30 (range 1–55) years. Conditioning for BMT consisted of cyclophosphamide and total body irradiation in 154 (96%) cases and graft-versus-host disease prophylaxis was the standard methotrexate and cyclosporine combination in 134 (83%) cases. Median post-transplant follow-up was 2.9 years. Leukemia-free survival (LFS) at 5 years was 50 ± 12% for transplants during first complete remission (n = 16), 28 ± 8% during second CR (n = 40), 27 ± 17% during subsequent CR (n = 8), 7 ± 3% during relapse (n = 81) and 19 ± 10% during primary induction failure (n = 16). The cumulative incidences of relapse were 19%, 23%, 25%, 44% and 63%, for the five groups, respectively. Transplantation during remission, a marrow cell dose above 3.5 × 108/kg, and cytomegalovirus seronegative status before BMT in both patient and donor were favorable prognostic factors. Adults in any CR who received a marrow cell dose above 3.5 × 108/mg had a LFS of 54 ± 9% at 5 years. These data extend our previous findings on the association between a high marrow cell dose and improved survival and support the use of unrelated donor BMT for treatment of patients with high risk AML when a family match is not available. Bone Marrow Transplantation (2000) 26, 397–404.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Gratwohl A, Hermans J . Bone marrow transplantation activity in Europe 1992: report from the European Group for Bone Marrow Transplantation Bone Marrow Transplant 1994 13: 5–10

    CAS  PubMed  Google Scholar 

  2. Gratwohl A, Hermans J . Indications and donor source of hematopoietic stem cell transplants in Europe 1993: report from the European Group for Blood and Marrow Transplantation Clin Transplant 1995 9: 355–363

    CAS  PubMed  Google Scholar 

  3. Gratwohl A, Hermans J, Baldomero H . Hematopoietic precursor cell transplants in Europe: activity in 1994. Report from the European Group for Blood and Marrow Transplantation Bone Marrow Transplant 1996 17: 137–148

    CAS  PubMed  Google Scholar 

  4. Gratwohl A, Hermans J, Baldomero H . Blood and marrow transplantation activity in Europe 1995 Bone Marrow Transplant 1997 19: 407–419

    Article  CAS  PubMed  Google Scholar 

  5. Gratwohl A . Blood and marrow transplantation activity in Europe 1996. Special report Bone Marrow Transplant 1998 22: 227–240

    Article  CAS  PubMed  Google Scholar 

  6. Gratwohl A, Passweg J, Baldomero H, Hermans J . Blood and marrow transplantation activity in Europe 1997 Bone Marrow Transplant 1999 24: 231–245

    Article  CAS  PubMed  Google Scholar 

  7. Anasetti C, Petersdorf EW, Martin PJ et al. Improving availability and safety of unrelated donor transplants Curr Opin Oncol 2000 12: 121–126

    Article  CAS  PubMed  Google Scholar 

  8. Petersdorf EW, Gooley T, Anasetti C et al. Optimizing outcome after unrelated marrow transplantation by comprehensive matching of HLA class I and II alleles in the donor and recipient Blood 1998 92: 3515–3520

    CAS  PubMed  Google Scholar 

  9. Sasazuki T, Juji T, Morishima Y et al. Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor New Engl J Med 1998 339: 1177–1185

    Article  CAS  PubMed  Google Scholar 

  10. Lamparelli T, Van Lint MT, Gualandi F et al. Bone marrow transplantation for chronic myeloid leukemia from unrelated and sibling donors: single center experience Bone Marrow Transplant 1997 20: 1057–1062

    Article  CAS  PubMed  Google Scholar 

  11. Hessner MJ, Endean DJ, Casper JT et al. Use of unrelated marrow grafts compensates for reduced graft-versus-leukemia reactivity after T-cell-depleted allogeneic marrow transplantation for chronic myelogenous leukemia Blood 1995 86: 3987–3996

    CAS  PubMed  Google Scholar 

  12. Sierra J, Storer B, Hansen JA et al. Transplantation of marrow cells from unrelated donors for treatment of high-risk acute leukemia: the effect of leukemic burden, donor HLA-matching, and marrow cell dose Blood 1997 89: 4226–4235

    CAS  PubMed  Google Scholar 

  13. Hansen JA, Mickelson EM, Choo SY et al. Clinical bone marrow transplantation: donor selection and recipient monitoring. In: Rose NR, De Macario EC, Fahey JL et al (eds) Manual of Clinical Laboratory Immunology, 4th edn American Society for Microbiology: Washington, DC 1992 850–867

    Google Scholar 

  14. Dupont B, Yang SY . Histocompatibility. In: Forman SJ, Blume KJ, Thomas ED (eds) Bone Marrow Transplantation Blackwell: Boston, MA 1994 22–40

    Google Scholar 

  15. Petersdorf EW, Smith AG, Mickelson EM et al. Ten HLA-DR4 alleles defined by sequence polymorphism within the DRB1 first domain Immunogenetics 1991 33: 267–275

    Article  CAS  PubMed  Google Scholar 

  16. Storb R, Deeg J, Pepe M et al. Methotrexate and cyclosporine versus cyclosporine alone for prophylaxis of graft-versus-host disease in patients given HLA-identical marrow grafts for leukemia: long-term follow-up of a controlled trial Blood 1989 73: 1729–1734

    CAS  PubMed  Google Scholar 

  17. Przepiorka D, Weisdorf D, Martin P et al. 1994 consensus conference on acute GVHD grading Bone Marrow Transplant 1995 15: 825–828

    CAS  PubMed  Google Scholar 

  18. Kaplan EL, Meier P . Nonparametric estimation for incomplete observations J Am Stat Assoc 1958 53: 457–481

    Article  Google Scholar 

  19. Kalbfleish JD, Prentice RL . The Statistical Analysis of Failure Time Data Wiley: New York 1980

    Google Scholar 

  20. Niland JC, Fisher LD . Biostatistical methods in marrow transplantation. In: Forman SJ, Blume KJ, Thomas ED (eds) Bone Marrow Transplantation Blackwell: Boston, MA 1994 242–258

    Google Scholar 

  21. Pepe MS, Longton G, Pettinger M et al. Summarizing data on survival, relapse, and chronic graft-versus-host disease after bone marrow transplantation: motivation for and description of new methods Br J Haematol 1993 83: 602–607

    Article  CAS  PubMed  Google Scholar 

  22. Clift R, Goldman J, Gratwohl A, Horowitz M . Proposals for standardized reporting of results of bone marrow transplantation for leukaemia Bone Marrow Transplant 1989 4: 445–448

    CAS  PubMed  Google Scholar 

  23. Busca A, Anasetti C, Anderson G et al. Unrelated donor or autologous marrow transplantation for treatment of acute leukemia Blood 1994 83: 3077–3084

    CAS  PubMed  Google Scholar 

  24. Balduzzi A, Gooley T, Anasetti C et al. Unrelated donor marrow transplantation in children Blood 1995 86: 3247–3256

    CAS  PubMed  Google Scholar 

  25. Ringdén O, Labopin M, Gluckman E et al. Donor search or autografting in patients with acute leukaemia who lack an HLA-identical sibling? A matched-pair analysis Bone Marrow Transplant 1997 19: 963–968

    Article  PubMed  Google Scholar 

  26. Consensus panel . A consensus statement on unrelated donor bone marrow transplantation from the consensus panel chaired by EC Gordon-Smith Bone Marrow Transplant 1997 19: 959–962

    Article  Google Scholar 

  27. Rowe JM, Liesveld JL . Treatment and prognostic factors in acute myeloid leukaemia Baillières Clin Haematol 1996 9: 87–105

    Article  CAS  PubMed  Google Scholar 

  28. Bloomfield CD, Lawrence D, Byrd JC et al. Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype Cancer Res 1998 58: 4173–4179

    CAS  PubMed  Google Scholar 

  29. Gale RP, Horowitz MM, Weiner RS et al. Impact of cytogenetic abnormalities on outcome of bone marrow transplants in acute myeloid leukemia in first remission Bone Marrow Transplant 1995 16: 203–208

    CAS  PubMed  Google Scholar 

  30. Ferrant A, Labopin M, Frassoni F et al. Karyotype in acute myeloblastic leukemia: prognostic significance for bone marrow transplantation in first remission. A European Group for Blood and Marrow Transplantation study Blood 1997 90: 2931–2938

    CAS  PubMed  Google Scholar 

  31. 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 Blood 1998 92: 2322–2333

    CAS  PubMed  Google Scholar 

  32. Labopin M, Gorin NC . Autologous bone marrow transplantation in 2502 patients with acute leukemia in Europe: a retrospective study Leukemia 1993 6: (Suppl. 4) 95–99

    Google Scholar 

  33. Goldman JM, Schmitz N, Niethammer D, Gratwohl A . Allogeneic and autologous transplantation for haematological diseases, solid tumors and immune disorders: current practice in Europe in 1998 Bone Marrow Transplant 1998 21: 1–7

    Article  CAS  PubMed  Google Scholar 

  34. Hansen JA, Gooley T, Martin PJ et al. Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia New Engl J Med 1998 338: 962–968

    Article  CAS  PubMed  Google Scholar 

  35. Demirer T, Gooley T, Buckner CD et al. Influence of total nucleated cell dose from marrow harvests on outcome in patients with acute myelogenous leukemia undergoing autologous transplantation Bone Marrow Transplant 1995 15: 907–913

    CAS  PubMed  Google Scholar 

  36. Neiderwieser D, Pepe M, Storb R et al. Improvement in rejection, engraftment rate and survival without increase in graft-versus-host disease by high marrow cell dose in patients transplanted for aplastic anaemia Br J Haematol 1988 69: 23–28

    Article  Google Scholar 

  37. Bortin M, Gale RP, Kay HEM, Rimm AA . Bone marrow transplantation for acute myelogenous leukemia. Factors associated with early mortality JAMA 1983 249: 1166–1172

    Article  CAS  PubMed  Google Scholar 

  38. Mavroudis D, Read E, Cottler-Fox M et al. CD34+ cell dose predicts survival, posttransplant morbidity, and rate of hematologic recovery after allogeneic marrow transplants for hematologic malignancies Blood 1996 88: 3223–3229

    CAS  PubMed  Google Scholar 

  39. Dini G, Lamparelli T, Rondelli D et al. Unrelated donor marrow transplantation for chronic myelogenous leukaemia Br J Haematol 1998 102: 544–552

    Article  CAS  PubMed  Google Scholar 

  40. Anderlini P, Korbling M, Sale D et al. Allogeneic blood stem cell transplantation: considerations for donors Blood 1997 90: 903–908

    CAS  PubMed  Google Scholar 

  41. Urbano-Ispizua A, Solano C, Brunet S et al. Allogeneic peripheral blood progenitor cell transplantation: analysis of short-term engraftment and acute GVHD incidence in 33 cases Bone Marrow Transplant 1996 18: 35–40

    CAS  PubMed  Google Scholar 

  42. Ottinger HD, Beelen DW, Scheulen B et al. Improved immune reconstitution after allotransplantation of peripheral blood stem cells instead of bone marrow Blood 1996 88: 2775–2779

    CAS  PubMed  Google Scholar 

  43. Ringden O, Remberger M, Runde V et al. Peripheral blood stem cell transplantation from unrelated donors: a comparison with marrow transplantation Blood 1999 94: 455–464

    CAS  PubMed  Google Scholar 

  44. Storek J, Gooley T, Siadak M et al. Allogeneic peripheral blood stem cell transplantation may be associated with a high risk of chronic graft-versus-host disease Blood 1997 90: 4705–4709

    CAS  PubMed  Google Scholar 

  45. Solano C, Martínez C, Brunet S et al. Chronic graft-versus-host disease after allogeneic peripheral blood progenitor cell or bone marrow transplantation from matched related donors. A case–control study Bone Marrow Transplant 1998 22: 1129–1135

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported in part by National Institutes of Health grants CA18029, CA18221, CA15704 and AI33484. Dr Sierra is a recipient of grant FIS 97/0626 from the Fondo de Investigaciones Sanitarias del Ministerio de Sanidad y Consumo, Spain. We would like to thank Amy Mellon for data management and Jennifer Brackensick for her skillful assistance in the preparation of the manuscript.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sierra, J., Storer, B., Hansen, J. et al. Unrelated donor marrow transplantation for acute myeloid leukemia: an update of the Seattle experience. Bone Marrow Transplant 26, 397–404 (2000). https://doi.org/10.1038/sj.bmt.1702519

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1702519

Keywords

This article is cited by

Search

Quick links