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Comparison of HLA-matched sibling and unrelated donor transplantation in adult patients with acquired severe aplastic anemia

Abstract

The recent improvements in the outcomes of severe aplastic anemia (SAA) patients who received allogeneic stem cell transplantation (SCT) from unrelated donors (URD) suggest the possibility of its alternative first-line treatment. To address this issue, results of adult SAA patients receiving allogeneic SCT were compared between the following three donor-type groups: 8/8–matched sibling (MSD; n = 153), 8/8 well-matched unrelated (WM-URD; n = 72), and 6–7/8 partially matched unrelated (PM-URD; n = 33). Proportion of patients who experienced immunosuppressive treatment failures was significantly higher in the URD groups than in the MSD group (P< 0.01). The incidences of graft failure and transplant-related mortality, and graft-vs.-host disease-free, failure-free survival rates of the MSD, WM-URD, and PM-URD groups were 14.6, 0, and 0% (P< 0.01); 6.1, 10.3, and 21.7% (P= 0.03); and 76.7, 55.5, and 51.5% (P< 0.01), respectively. The overall survival (OS) rate of the MSD group (93.9%) was higher than that of the PM-URD (78.3%; P < 0.01) group, but not to that of the WM-URD (86.2%; P= 0.18) group. Our study showed comparable OS between the MSD group and WM-URD group, which suggest that the URD-SCT can be used as a first-line treatment for adult SAA patients with WM-URD.

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Fig. 1: Transplant outcomes according to donor-type groups.
Fig. 2: Transplant outcomes according to donor-type groups for the propensity-score matching cohort of patients receiving SCT as a first-line treatment.

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References

  1. Shin SH, Lee SE, Lee JW. Recent advances in treatment of aplastic anemia. Korean J Intern Med. 2014;29:713–26.

    Article  Google Scholar 

  2. Scheinberg P, Young NS. How I treat acquired aplastic anemia. Blood. 2012;120:1185–96.

    Article  CAS  Google Scholar 

  3. Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, et al. Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol. 2016;172:187–207.

    Article  Google Scholar 

  4. Deeg HJ, O’Donnell M, Tolar J, Agarwal R, Harris RE, Feig SA, et al. Optimization of conditioning for marrow transplantation from unrelated donors for patients with aplastic anemia after failure of immunosuppressive therapy. Blood. 2006;108:1485–91.

    Article  CAS  Google Scholar 

  5. Kojima S, Matsuyama T, Kato S, Kigasawa H, Kobayashi R, Kikuta A, et al. Outcome of 154 patients with severe aplastic anemia who received transplants from unrelated donors: the Japan Marrow Donor Program. Blood. 2002;100:799–803.

    Article  CAS  Google Scholar 

  6. Passweg JR, Perez WS, Eapen M, Camitta BM, Gluckman E, Hinterberger W, et al. Bone marrow transplants from mismatched related and unrelated donors for severe aplastic anemia. Bone Marrow Transpl. 2006;37:641–9.

    Article  CAS  Google Scholar 

  7. Shin SH, Lee JW. The optimal immunosuppressive therapy for aplastic anemia. Int J Hematol. 2013;97:564–72.

    Article  CAS  Google Scholar 

  8. Maury S, Balere-Appert ML, Chir Z, Boiron JM, Galambrun C, Yakouben K, et al. Unrelated stem cell transplantation for severe acquired aplastic anemia: improved outcome in the era of high-resolution HLA matching between donor and recipient. Haematologica. 2007;92:589–96.

    Article  Google Scholar 

  9. Viollier R, Socie G, Tichelli A, Bacigalupo A, Korthof ET, Marsh J, et al. Recent improvement in outcome of unrelated donor transplantation for aplastic anemia. Bone Marrow Transpl. 2008;41:45–50.

    Article  CAS  Google Scholar 

  10. Yagasaki H, Takahashi Y, Hama A, Kudo K, Nishio N, Muramatsu H, et al. Comparison of matched-sibling donor BMT and unrelated donor BMT in children and adolescent with acquired severe aplastic anemia. Bone Marrow Transpl. 2010;45:1508–13.

    Article  CAS  Google Scholar 

  11. Dufour C, Veys P, Carraro E, Bhatnagar N, Pillon M, Wynn R, et al. Similar outcome of upfront-unrelated and matched sibling stem cell transplantation in idiopathic paediatric aplastic anaemia. A study on behalf of the UK Paediatric BMT Working Party, Paediatric Diseases Working Party and Severe Aplastic Anaemia Working Party of EBMT. Br J Haematol. 2015;171:585–94.

    Article  CAS  Google Scholar 

  12. Marsh JCW, Risitano AM, Mufti GJ. The case for upfront HLA-matched unrelated donor hematopoietic stem cell transplantation as a curative option for adult acquired severe aplastic anemia. Biol Blood Marrow Transpl. 2019;25:e277–84.

    Article  Google Scholar 

  13. Zhang Y, Wu L, Mo W, Zhou M, Li Y, Chen X, et al. Comparable outcomes of first-line hematopoietic stem cell transplantation from unrelated and matched sibling donors in adult patients with aplastic anemia: a retrospective single-center study. Biol Blood Marrow Transpl. 2019;25:1567–75.

    Article  Google Scholar 

  14. Vaht K, Goransson M, Carlson K, Isaksson C, Lenhoff S, Sandstedt A, et al. High graft-versus-host disease-free, relapse/rejection-free survival and similar outcome of related and unrelated allogeneic stem cell transplantation for aplastic anemia: a nationwide swedish cohort study. Biol Blood Marrow Transpl. 2019;25:1970–4.

    Article  Google Scholar 

  15. Park SS, Kwak DH, Jeon YW, Yoon JH, Lee SE, Cho BS, et al. Beneficial role of low-dose antithymocyte globulin in unrelated stem cell transplantation for adult patients with acquired severe aplastic anemia: reduction of graft-versus-host disease and improvement of graft-versus-host disease-free, failure-free survival rate. Biol Blood Marrow Transpl. 2017;23:1498–508.

    Article  CAS  Google Scholar 

  16. Shin SH, Jeon YW, Yoon JH, Yahng SA, Lee SE, Cho BS, et al. Comparable outcomes between younger (40 years) and older (>40 years) adult patients with severe aplastic anemia after HLA-matched sibling stem cell transplantation using fludarabine-based conditioning. Bone Marrow Transpl. 2016;51:1456–63.

    Article  CAS  Google Scholar 

  17. Camitta BM, Storb R, Thomas ED. Aplastic anemia (first of two parts): pathogenesis, diagnosis, treatment, and prognosis. N. Engl J Med. 1982;306:645–52.

    Article  CAS  Google Scholar 

  18. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912–9.

    Article  CAS  Google Scholar 

  19. Champlin RE, Perez WS, Passweg JR, Klein JP, Camitta BM, Gluckman E, et al. Bone marrow transplantation for severe aplastic anemia: a randomized controlled study of conditioning regimens. Blood. 2007;109:4582–5.

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

  21. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transpl. 2005;11:945–56.

    Article  Google Scholar 

  22. McDonald GB, Hinds MS, Fisher LD, Schoch HG, Wolford JL, Banaji M, et al. Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Ann Intern Med. 1993;118:255–67.

    Article  CAS  Google Scholar 

  23. Silva Lde P, Patah PA, Saliba RM, Szewczyk NA, Gilman L, Neumann J, et al. Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplants is the complex result of BK virus infection, preparative regimen intensity and donor type. Haematologica. 2010;95:1183–90.

    Article  Google Scholar 

  24. The National Cancer Institute Common Terminology Criteria for adverse events version 3.0. Available at: Common Terminology Criteria for Adverse Events v3.0. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf. Accessed 17 January 2020.

  25. Holtan SG, DeFor TE, Lazaryan A, Bejanyan N, Arora M, Brunstein CG, et al. Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood. 2015;125:1333–8.

    Article  CAS  Google Scholar 

  26. Austin PC. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivar Behav Res. 2011;46:399–424.

    Article  Google Scholar 

  27. Bacigalupo A, Socie G, Hamladji RM, Aljurf M, Maschan A, Kyrcz-Krzemien S, et al. Current outcome of HLA identical sibling versus unrelated donor transplants in severe aplastic anemia: an EBMT analysis. Haematologica. 2015;100:696–702.

    Article  Google Scholar 

  28. Bacigalupo A, Socie G, Schrezenmeier H, Tichelli A, Locasciulli A, Fuehrer M, et al. Bone marrow versus peripheral blood as the stem cell source for sibling transplants in acquired aplastic anemia: survival advantage for bone marrow in all age groups. Haematologica. 2012;97:1142–8.

    Article  CAS  Google Scholar 

  29. Schrezenmeier H, Passweg JR, Marsh JC, Bacigalupo A, Bredeson CN, Bullorsky E, et al. Worse outcome and more chronic GVHD with peripheral blood progenitor cells than bone marrow in HLA-matched sibling donor transplants for young patients with severe acquired aplastic anemia. Blood. 2007;110:1397–400.

    Article  CAS  Google Scholar 

  30. Eapen M, Le Rademacher J, Antin JH, Champlin RE, Carreras J, Fay J, et al. Effect of stem cell source on outcomes after unrelated donor transplantation in severe aplastic anemia. Blood. 2011;118:2618–21.

    Article  CAS  Google Scholar 

  31. MacMillan ML, Robin M, Harris AC, DeFor TE, Martin PJ, Alousi A, et al. A refined risk score for acute graft-versus-host disease that predicts response to initial therapy, survival, and transplant-related mortality. Biol Blood Marrow Transpl. 2015;21:761–7.

    Article  Google Scholar 

  32. Fiuza-Luces C, Simpson RJ, Ramirez M, Lucia A, Berger NA. Physical function and quality of life in patients with chronic GvHD: a summary of preclinical and clinical studies and a call for exercise intervention trials in patients. Bone Marrow Transpl. 2016;51:13–26.

    Article  CAS  Google Scholar 

  33. Servais S, Beguin Y, Delens L, Ehx G, Fransolet G, Hannon M, et al. Novel approaches for preventing acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Expert Opin Investig Drugs. 2016;25:957–72.

    Article  CAS  Google Scholar 

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Correspondence to Jong Wook Lee.

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Shin, S.H., Park, S.S., Yoon, J.H. et al. Comparison of HLA-matched sibling and unrelated donor transplantation in adult patients with acquired severe aplastic anemia. Bone Marrow Transplant 55, 1570–1579 (2020). https://doi.org/10.1038/s41409-020-0820-x

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