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.

  • Article
  • Published:

The improvement in overall survival from unrelated donor transplantation in Australia and New Zealand is driven by a reduction in non-relapse mortality: A study from the ABMTRR

Bone Marrow Transplantation volume 57, pages 982–989 (2022)Cite this article

Subjects

Abstract

Unrelated donors (UDs) are the commonest source for allogeneic transplantation (alloSCT), with higher non-relapse mortality (NRM) than siblings. We analyzed data from the Australasian Bone Marrow Transplant Recipient Registry from adults receiving a first UD alloSCT during 2001–2015, to determine whether and how NRM has changed. Predictors of outcome were determined using cox regression, accounting for time-interactions and competing risks. A total of 2308 patients met inclusion criteria. Changes over time included increasing age, utilization of peripheral blood cells, reduced intensity conditioning, and T-cell depletion. Three-year OS increased significantly from 44% in 2001–2005 to 58% in 2011–2015 (p < 0.001). This was attributed to a reduction in NRM from 35% to 24% (p < 0.001) with no change in relapse. Factors associated with increased NRM included age, male sex, CMV seropositivity, HLA mismatch, transplant more than 6 months from diagnosis, and T-cell depletion when administered during 2001–2005. Survival following UD SCT has improved by almost 15% over the past decade, driven by improvements in NRM. This has occurred despite increasing recipient age and appears to be due to better donor selection, reduced delays to transplantation, and improved prevention and management of GVHD.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

Data sharing requests may be sent to the corresponding author David Kliman, at David.Kliman@health.nsw.gov.au.

References

  1. Nivison-Smith I, Bardy P, Dodds AJ, Ma DDF, Aarons D, Tran S, et al. A review of hematopoietic cell transplantation in Australia and New Zealand, 2005 to 2013. Biol Blood Marrow Transpl. 2016;22:284–91.

    Article  Google Scholar 

  2. Hahn T, McCarthy PL Jr, Hassebroek A, Bredeson C, Gajewski JL, Hale GA, et al. Significant improvement in survival after allogeneic hematopoietic cell transplantation during a period of significantly increased use, older recipient age, and use of unrelated donors. J Clin Oncol. 2013;31:2437–49.

    Article  Google Scholar 

  3. Gratwohl A, Pasquini MC, Aljurf M, Atsuta Y, Baldomero H, Foeken L, et al. One million haemopoietic stem-cell transplants: a retrospective observational study. Lancet Haematol. 2015;2:e91–e100.

    Article  Google Scholar 

  4. Nivison-Smith I, Dodds AJ, Dunckley H, Ma DD, Moore JJ, Simpson JM, et al. Increased activity and improved outcome in unrelated donor haemopoietic cell transplants for acute myeloid leukaemia in Australia, 1992–2005. Intern Med J. 2011;41:27–34.

    Article  CAS  Google Scholar 

  5. Gratwohl A, Baldomero H, Gratwohl M, Aljurf M, Bouzas LF, Horowitz M, et al. Quantitative and qualitative differences in use and trends of hematopoietic stem cell transplantation: a global observational study. Haematologica. 2013;98:1282–90.

    Article  Google Scholar 

  6. D’Souza A, Lee S, Zhu X, Pasquini M. Current use and trends in hematopoietic cell transplantation in the United States. Biol Blood Marrow Transpl. 2017;23:1417–21.

    Article  Google Scholar 

  7. McDonald GB, Sandmaier BM, Mielcarek M, Sorror M, Pergam SA, Cheng G-S, et al. Survival, nonrelapse mortality, and relapse-related mortality after allogeneic hematopoietic cell transplantation: comparing 2003–2007 versus 2013–2017 cohorts. Ann Intern Med. 2020;172:229.

    Article  Google Scholar 

  8. Szydlo R, Goldman JM, Klein JP, Gale RP, Ash RC, Bach FH, et al. Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings. J Clin Oncol. 1997;15:1767–77.

    Article  CAS  Google Scholar 

  9. McGlave PB, Shu XO, Wen W, Anasetti C, Nademanee A, Champlin R, et al. Unrelated donor marrow transplantation for chronic myelogenous leukemia: 9 years’ experience of the national marrow donor program. Blood. 2000;95:2219–25.

    Article  CAS  Google Scholar 

  10. Moore J, Nivison-Smith I, Goh K, Ma D, Bradstock K, Szer J, et al. Equivalent survival for sibling and unrelated donor allogeneic stem cell transplantation for acute myelogenous leukemia. Biol Blood Marrow Transpl. 2007;13:601–7.

    Article  Google Scholar 

  11. Walter RB, Pagel JM, Gooley TA, Petersdorf EW, Sorror ML, Woolfrey AE, et al. Comparison of matched unrelated and matched related donor myeloablative hematopoietic cell transplantation for adults with acute myeloid leukemia in first remission. Leukemia. 2010;24:1276–82.

    Article  CAS  Google Scholar 

  12. Gupta V, Tallman MS, He W, Logan BR, Copelan E, Gale RP, et al. Comparable survival after HLA-well-matched unrelated or matched sibling donor transplantation for acute myeloid leukemia in first remission with unfavorable cytogenetics at diagnosis. Blood. 2010;116:1839–48.

    Article  CAS  Google Scholar 

  13. Majhail NS, Chitphakdithai P, Logan B, King R, Devine S, Rossmann SN, et al. Significant improvement in survival after unrelated donor hematopoietic cell transplantation in the recent era. Biol Blood Marrow Transpl. 2015;21:142–50.

    Article  Google Scholar 

  14. Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N. Engl J Med. 2010;363:2091–101.

    Article  CAS  Google Scholar 

  15. Barrett J. Why is a 3-year NRM following allogeneic transplantation still stuck at approximately 20%? Best Pr Res Clin Haematol. 2018;31:414–9.

    Article  Google Scholar 

  16. Shouval R, Fein JA, Labopin M, Kröger N, Duarte RF, Bader P, et al. Outcomes of allogeneic haematopoietic stem cell transplantation from HLA-matched and alternative donors: a European Society for Blood and Marrow Transplantation registry retrospective analysis. Lancet Haematol. 2019;6:e573–84.

    Article  Google Scholar 

  17. Penack O, Peczynski C, Mohty M, Yakoub-Agha I, Styczynski J, Montoto S, et al. How much has allogeneic stem cell transplant-related mortality improved since the 1980s? A retrospective analysis from the EBMT. Blood Adv. 2020;4:6283–90.

    Article  CAS  Google Scholar 

  18. Walker I, Panzarella T, Couban S, Couture F, Devins G, Elemary M, et al. Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from unrelated donors: a randomised, controlled, open-label, phase 3, multicentre trial. Lancet Oncol. 2016;17:164–73.

    Article  CAS  Google Scholar 

  19. Weisdorf D, Spellman S, Haagenson M, Horowitz M, Lee S, Anasetti C, et al. Classification of HLA-matching for retrospective analysis of unrelated donor transplantation: revised definitions to predict survival. Biol Blood Marrow Transpl. 2008;14:748–58.

    Article  Google Scholar 

  20. Lee SJ, Klein J, Haagenson M, Baxter-Lowe LA, Confer DL, Eapen M, et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood. 2007;110:4576–83.

    Article  CAS  Google Scholar 

  21. Teira P, Battiwalla M, Ramanathan M, Barrett AJ, Ahn KW, Chen M, et al. Early cytomegalovirus reactivation remains associated with increased transplant-related mortality in the current era: a CIBMTR analysis. Blood. 2016;127:2427–38.

    Article  CAS  Google Scholar 

  22. Xie H, Sandmaier BM, Mast TC, Sahoo F, Green ML, Jerome KR, et al. Cytomegalovirus viral load and mortality after haemopoietic stem cell transplantation in the era of pre-emptive therapy: a retrospective cohort study. Lancet Haematol. 2016;3:e119–27.

    Article  Google Scholar 

  23. Gratwohl A, Stern M, Brand R, Apperley J, Baldomero H, de Witte T, et al. Risk score for outcome after allogeneic hematopoietic stem cell transplantation: a retrospective analysis. Cancer. 2009;115:4715–26.

    Article  Google Scholar 

  24. Versluis J, Labopin M, Niederwieser D, Socie G, Schlenk RF, Milpied N, et al. Prediction of non-relapse mortality in recipients of reduced intensity conditioning allogeneic stem cell transplantation with AML in first complete remission. Leukemia. 2015;29:51–7.

    Article  CAS  Google Scholar 

  25. Bacigalupo A, Lamparelli T, Barisione G, Bruzzi P, Guidi S, Alessandrino PE, et al. Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation. Biol Blood Marrow Transpl. 2006;12:560–5.

    Article  Google Scholar 

  26. Chang Y, Wu D, Lai Y, Liu Q, Sun Y, Hu J et al. Antithymocyte globulin for matched sibling donor transplantation in patients with hematologic malignancies: a multicenter, open-label, randomized controlled study. J Clin Oncol. 2020;38:3367–76.

  27. Soiffer RJ, Kim HT, McGuirk J, Horwitz ME, Johnston L, Patnaik MM, et al. Prospective, randomized, double-blind, phase III clinical trial of anti–t-lymphocyte globulin to assess impact on chronic graft-versus-host disease–free survival in patients undergoing HLA-matched unrelated myeloablative hematopoietic cell transplantation. J Clin Oncol. 2017;35:4003–11.

    Article  CAS  Google Scholar 

  28. Kroger N, Solano C, Wolschke C, Bandini G, Patriarca F, Pini M, et al. Antilymphocyte globulin for prevention of chronic graft-versus-host disease. N. Engl J Med. 2016;374:43–53.

    Article  Google Scholar 

  29. Finke J, Schmoor C, Bethge WA, Ottinger H, Stelljes M, Volin L, et al. Long-term outcomes after standard graft-versus-host disease prophylaxis with or without anti-human-T-lymphocyte immunoglobulin in haemopoietic cell transplantation from matched unrelated donors: final results of a randomised controlled trial. Lancet Haematol. 2017;4:e293–e301.

    Article  Google Scholar 

  30. Mielcarek M, Furlong T, O’Donnell PV, Storer BE, McCune JS, Storb R, et al. Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation. Blood. 2016;127:1502–8.

    Article  CAS  Google Scholar 

  31. Moiseev IS, Pirogova OV, Alyanski AL, Babenko EV, Gindina TL, Darskaya EI, et al. Risk‐adapted GVHD prophylaxis with post‐transplantation cyclophosphamide in adults after related, unrelated, and haploidentical transplantations. Eur J Haematol. 2018;100:395–402.

    Article  CAS  Google Scholar 

  32. Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, et al. National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 diagnosis and staging working group report. Biol Blood Marrow Transpl. 2015;21:389–401.

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge and thank Leonie Wilcox, Donna Aaron, Ian Nivison-Smith, and Sumit Katyal from the ABMTRR, the Australian Bone Marrow Donor Registry, as well as the clinicians, scientists and patients at all of the corresponding transplant centers.

Author information

Author notes

  1. These authors contributed equally: Nada Hamad, John Moore.

Authors and Affiliations

  1. Department of Haematology and Stem Cell Transplantation, St Vincent’s Hospital, Sydney, NSW, Australia

    David Kliman, Nada Hamad & John Moore

  2. Australasian Bone Marrow Transplant Recipient Registry, Sydney, NSW, Australia

    Steven Tran

  3. Haematology and Bone Marrow Transplant Service, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia

    Glen Kennedy, Cameron Curley & Angela McLean

  4. Blood Transplant and Cell Therapies Program, Westmead Hospital, Sydney, NSW, Australia

    David Gottlieb & John Kwan

  5. Department of Haematology and BMT, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC, Australia

    David Ritchie & Lynette Chee

  6. Malignant Haematology and Stem Cell Transplantation Service, Alfred Hospital, Melbourne, VIC, Australia

    Andrew Spencer

  7. Blood and Marrow Transplant Program, Fiona Stanley Hospital, Perth, WA, Australia

    Duncan Purtill

  8. Haematology and Bone Marrow Transplant Unit, Royal Adelaide Hospital, Adelaide, SA, Australia

    Peter Bardy

  9. Institute of Haematology, Royal Prince Alfred Hospital, Sydney, NSW, Australia

    Stephen Larsen

  10. Clinical Haematology Service and Stem Cell Transplant Program, Auckland City Hospital, Auckland, New Zealand

    Nicole Chien

  11. Wellington Blood and Cancer Centre, Wellington Hospital, Wellington, New Zealand

    Travis Perera

  12. Department of Haematology, Royal North Shore Hospital, Sydney, NSW, Australia

    Matthew Greenwood

Authors
  1. David Kliman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Steven Tran
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Glen Kennedy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cameron Curley
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Angela McLean
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. David Gottlieb
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. John Kwan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. David Ritchie
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lynette Chee
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Andrew Spencer
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Duncan Purtill
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Peter Bardy
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Stephen Larsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Nicole Chien
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Travis Perera
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Matthew Greenwood
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Nada Hamad
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. John Moore
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

DK and JM conceived the study. DK, ST, and JM performed the statistical analysis. DK wrote the manuscript with supervision from ST, NH, and JM. All remaining authors are from centers that provided data, analyzed the results, assisted in shaping the discussion, and provided critical comments to revise the manuscript.

Corresponding author

Correspondence to David Kliman.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kliman, D., Tran, S., Kennedy, G. et al. The improvement in overall survival from unrelated donor transplantation in Australia and New Zealand is driven by a reduction in non-relapse mortality: A study from the ABMTRR. Bone Marrow Transplant 57, 982–989 (2022). https://doi.org/10.1038/s41409-022-01683-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-022-01683-w

Search

Advanced search

Quick links