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Patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation: trends in survival during the past two decades

Abstract

It remains unclear how specific innovations in allogeneic hematopoietic cell transplantation (HCT) attained over the past decades have contributed to improvement in transplantation outcomes. To address this question, we conducted a registry-based study of adults with acute myeloid leukemia in first or second complete remission who underwent allogeneic HCT between 1994 and 2013 from a sibling (N = 1600) or unrelated (N = 2113) donor matched at the antigen level for HLA-A, -B, and -DR. Preliminary analysis led us to focus on comparisons between the 1994–2006 and 2007–2013 periods. Significant improvement in survival was observed in the later cohort compared to the earlier cohort for unrelated HCT (P = 0.004), but not for related HCT (P = 0.767). The improvement in unrelated HCT was solely due to diminished non-relapse mortality (P = 0.001), while incidence of relapse did not change over time (P = 0.934). The percentage of patients receiving transplants from 8/8-matched unrelated donors was significantly higher in the later cohort (P < 0.001), and their survival was significantly better than that of those undergoing mismatched unrelated HCT (P = 0.022). These findings suggest that advances in HLA-typing technology have been vital for improvement in transplantation outcomes.

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References

  1. 1.

    Gupta V, Tallman MS, Weisdorf DJ. Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia: myths, controversies, and unknowns. Blood. 2011;117:2307–18.

  2. 2.

    Yanada M. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia during first complete remission: a clinical perspective. Int J Hematol. 2015;101:243–54.

  3. 3.

    Cornelissen JJ, Blaise D. Hematopoietic stem cell transplantation for patients with AML in first complete remission. Blood. 2016;127:62–70.

  4. 4.

    Atsuta Y, Suzuki R, Yoshimi A, Gondo H, Tanaka J, Hiraoka A, et al. Unification of hematopoietic stem cell transplantation registries in Japan and establishment of the TRUMP System. Int J Hematol. 2007;86:269–74.

  5. 5.

    Atsuta Y. Introduction of Transplant Registry Unified Management Program 2 (TRUMP2): scripts for TRUMP data analyses, part I (variables other than HLA-related data). Int J Hematol. 2016;103:3–10.

  6. 6.

    Kanda J. Scripts for TRUMP data analyses. Part II (HLA-related data): statistical analyses specific for hematopoietic stem cell transplantation. Int J Hematol. 2016;103:11–9.

  7. 7.

    Morishima Y, Sasazuki T, Inoko H, Juji T, Akaza T, Yamamoto K, et al. The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors. Blood. 2002;99:4200–6.

  8. 8.

    Kanda Y, Kanda J, Atsuta Y, Maeda Y, Ichinohe T, Ohashi K, et al. Impact of a single human leucocyte antigen (HLA) allele mismatch on the outcome of unrelated bone marrow transplantation over two time periods. A retrospective analysis of 3003 patients from the HLA Working Group of the Japan Society for Blood and Marrow Transplantation. Br J Haematol. 2013;161:566–77.

  9. 9.

    Sullivan KM, Agura E, Anasetti C, Appelbaum F, Badger C, Bearman S, et al. Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol. 1991;28:250–9.

  10. 10.

    Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15:825–8.

  11. 11.

    Giralt S, Logan B, Rizzo D, Zhang MJ, Ballen K, Emmanouilides C, et al. Reduced-intensity conditioning for unrelated donor progenitor cell transplantation: long-term follow-up of the first 285 reported to the national marrow donor program. Biol Blood Marrow Transplant. 2007;13:844–52.

  12. 12.

    Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15:1628–33.

  13. 13.

    O’Donnell MR, Tallman MS, Abboud CN, Altman JK, Appelbaum FR, Arber DA et al. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology. acute myeloid leukemia. version 1.2016. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed on 26 Feb 2016.

  14. 14.

    Yanada M, Mori J, Aoki J, Harada K, Mizuno S, Uchida N, et al. Effect of cytogenetic risk status on outcomes for patients with acute myeloid leukemia undergoing various types of allogeneic hematopoietic cell transplantation: an analysis of 7812 patients. Leuk Lymphoma. 2018;59:601–9.

  15. 15.

    Vicente D, Lamparelli T, Gualandi F, Occhini D, Raiola AM, Ibatici A, et al. Improved outcome in young adults with de novo acute myeloid leukemia in first remission, undergoing an allogeneic bone marrow transplant. Bone Marrow Transplant. 2007;40:349–54.

  16. 16.

    Giebel S, Labopin M, Holowiecki J, Labar B, Komarnicki M, Koza V, et al. Outcome of HLA-matched related allogeneic hematopoietic stem cell transplantation for patients with acute leukemia in first complete remission treated in Eastern European centers. Better results in recent years. Ann Hematol. 2009;88:1005–13.

  17. 17.

    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.

  18. 18.

    Horan JT, Logan BR, Agovi-Johnson MA, Lazarus HM, Bacigalupo AA, Ballen KK, et al. Reducing the risk for transplantation-related mortality after allogeneic hematopoietic cell transplantation: how much progress has been made? J Clin Oncol. 2011;29:805–13.

  19. 19.

    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.

  20. 20.

    Remberger M, Ackefors M, Berglund S, Blennow O, Dahllof G, Dlugosz A, et al. Improved survival after allogeneic hematopoietic stem cell transplantation in recent years. A single-center study. Biol Blood Marrow Transplant. 2011;17:1688–97.

  21. 21.

    Hahn T, McCarthy PL Jr, Hassebroek A, Bredeson C, Gajewski JL, 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.

  22. 22.

    Kurosawa S, Yakushijin K, Yamaguchi T, Atsuta Y, Nagamura-Inoue T, Akiyama H, et al. Changes in incidence and causes of non-relapse mortality after allogeneic hematopoietic cell transplantation in patients with acute leukemia/myelodysplastic syndrome: an analysis of the Japan Transplant Outcome Registry. Bone Marrow Transplant. 2013;48:529–36.

  23. 23.

    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 Transplant. 2015;21:142–50.

  24. 24.

    Gratwohl A, Sureda A, Cornelissen J, Apperley J, Dreger P, Duarte R, et al. Alloreactivity: the Janus-face of hematopoietic stem cell transplantation. Leukemia. 2017;31:1752–9.

  25. 25.

    Yanada M, Kurosawa S, Kobayashi T, Ozawa Y, Kanamori H, Kobayashi N, et al. Reduced-intensity conditioning allogeneic hematopoietic cell transplantation for younger patients with acute myeloid leukemia: a registry-based study. Bone Marrow Transplant. 2017;52:818–24.

  26. 26.

    Bornhauser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, et al. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012;13:1035–44.

  27. 27.

    Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, et al. Myeloablative versus reduced-intensity hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes. J Clin Oncol. 2017;35:1154–61.

  28. 28.

    Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, et al. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015;16:1525–36.

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Acknowledgements

This work was supported in part by the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) from Japan Agency for Medical Research and Development (AMED) under the grant number 18ek0510023h0002.

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Correspondence to Masamitsu Yanada.

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The authors declare that they have no conflict of interest.

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