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Short-term clinical outcomes after HLA 1-locus mismatched uPBSCT are similar to that after HLA-matched uPBSCT and uBMT

  • Shigeo FujiEmail author
  • Koichi Miyamura
  • Yoshinobu Kanda
  • Takahiro Fukuda
  • Takeshi Kobayashi
  • Yukiyasu Ozawa
  • Koji Iwato
  • Naoyuki Uchida
  • Tetsuya Eto
  • Takashi Ashida
  • Takehiko Mori
  • Masashi Sawa
  • Tatsuo Ichinohe
  • Yoshiko Atsuta
  • Junya Kanda
  • the HLA Working Group of the Japan Society for Hematopoietic Cell Transplantation
Original Article
  • 25 Downloads

Abstract

In Japan, use of unrelated peripheral blood stem cell transplantation (uPBSCT) from HLA-mismatched unrelated donors has recently been approved. We compared outcomes between HLA-matched and 1-locus mismatched uPBSCT, as well as the impact of HLA disparity in uPBSCT and in unrelated bone marrow transplantation (uBMT). In total, 5862 uBMT recipients and 234 uPBSCT recipients were included. In terms of HLA allele disparity, 185 uPBSCT patients (79.1%) had no HLA mismatch, and 49 (20.9%) had 1-locus mismatch; in comparison, 3585 uBMT patients (61.2%) had no HLA mismatch, and 2277 (38.8%) had 1-locus mismatch. The impact of 1-locus mismatch as compared with match in uPBSCT was not significantly higher than in uBMT [hazard ratio (HR) = 1.02 and 1.27 for grade III–IV acute graft-versus-host disease, HR = 0.98 and 1.14 for non-relapse mortality, and HR = 0.87 and 1.06 for overall survival, respectively]. In conclusion, the impact of single-locus mismatch on short-term outcomes was comparable in uPBSCT and uBMT. Larger studies with longer follow-up are needed to assess long-term outcomes.

Keywords

Peripheral blood stem cell transplantation HLA disparity Anti-thymocyte globulin 

Notes

Acknowledgements

This study was supported by Health, Labour and Welfare Science Grants for Research on Measures for Rare and Intractable Diseases from the Japanese Government.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

12185_2019_2631_MOESM1_ESM.docx (12 kb)
Supplementary material 1 (DOCX 12 KB)
12185_2019_2631_MOESM2_ESM.pdf (159 kb)
Supplementary material 2 (PDF 158 KB)

References

  1. 1.
    Sakai R, Taguri M, Oshima K, Mori T, Ago H, Adachi S, et al. A comparison of tacrolimus and cyclosporine combined with methotrexate for graft-versus-host disease prophylaxis, stratified by stem cell source: a retrospective nationwide survey. Int J Hematol. 2016;103:322–33.CrossRefPubMedGoogle Scholar
  2. 2.
    Kanda J, Saji H, Fukuda T, Kobayashi T, Miyamura K, Eto T, et al. Related transplantation with HLA-1 Ag mismatch in the GVH direction and HLA-8/8 allele-matched unrelated transplantation: a nationwide retrospective study. Blood. 2012;119:2409–16.CrossRefPubMedGoogle Scholar
  3. 3.
    Saito H, Ito M, Kato S, Kodera Y, Okamoto S, Taniguchi S, et al. The Japan Marrow Donor Program, 25 years of experience in achieving 20,000 bone marrow transplantations: organization structure, activity, and financial basis. Bone Marrow Transpl. 2018;53:609–16.CrossRefGoogle Scholar
  4. 4.
    Goto T, Tanaka T, Sawa M, Ueda Y, Ago H, Chiba S, et al. Prospective observational study on the first 51 cases of peripheral blood stem cell transplantation from unrelated donors in Japan. Int J Hematol. 2018;107:211–21.CrossRefPubMedGoogle Scholar
  5. 5.
    Passweg JR, Baldomero H, Bader P, Bonini C, Duarte RF, Dufour C, et al. Use of haploidentical stem cell transplantation continues to increase: the 2015 European Society for Blood and Marrow Transplant activity survey report. Bone Marrow Transpl. 2017;52:811–7.CrossRefGoogle Scholar
  6. 6.
    Khera N, Mau LW, Denzen EM, Meyer C, Houg K, Lee SJ, et al. Translation of clinical research into practice: an impact assessment of the results from the blood and marrow transplant Clinical Trials Network Protocol 0201 on Unrelated Graft Source Utilization. Biol Blood Marrow Transpl. 2018;24:2204–2210CrossRefGoogle Scholar
  7. 7.
    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.CrossRefPubMedGoogle Scholar
  8. 8.
    Giralt S, Ballen K, Rizzo D, Bacigalupo A, Horowitz M, Pasquini M, et al. Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transpl. 2009;15:367–9.CrossRefGoogle Scholar
  9. 9.
    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.Google Scholar
  10. 10.
    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.PubMedGoogle Scholar
  11. 11.
    Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med. 1999;18:695–706.CrossRefPubMedGoogle Scholar
  12. 12.
    Fine JP, Gray RJ. Fine JP. Gray RJA proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.CrossRefGoogle Scholar
  13. 13.
    Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transpl. 2013;48:452–8.CrossRefGoogle Scholar
  14. 14.
    Nagafuji K, Matsuo K, Teshima T, Mori S, Sakamaki H, Hidaka M, et al. Peripheral blood stem cell versus bone marrow transplantation from HLA-identical sibling donors in patients with leukemia: a propensity score-based comparison from the Japan Society for Hematopoietic Stem Cell Transplantation registry. Int J Hematol. 2010;91:855–64.CrossRefPubMedGoogle Scholar
  15. 15.
    Finke J, Bethge WA, Schmoor C, Ottinger HD, Stelljes M, Zander AR, et al. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol. 2009;10:855–64.CrossRefPubMedGoogle Scholar
  16. 16.
    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:e293–301.CrossRefPubMedGoogle Scholar
  17. 17.
    Kawamura K, Kanda J, Fuji S, Murata M, Ikegame K, Yoshioka K, et al. Impact of the presence of HLA 1-locus mismatch and the use of low-dose antithymocyte globulin in unrelated bone marrow transplantation. Bone Marrow Transpl. 2017;52:1390–8.CrossRefGoogle Scholar
  18. 18.
    Kuriyama K, Fuji S, Inamoto Y, Tajima K, Tanaka T, Inoue Y, et al. Impact of low-dose rabbit anti-thymocyte globulin in unrelated hematopoietic stem cell transplantation. Int J Hematol. 2016;103:453–60.CrossRefPubMedGoogle Scholar
  19. 19.
    Shichijo T, Fuji S, Tajima K, Kubo H, Nozaki K, Honda T, et al. Beneficial impact of low-dose rabbit anti-thymocyte globulin in unrelated hematopoietic stem cell transplantation: focusing on difference between stem cell sources. Bone Marrow Transpl. 2018;103:453–460Google Scholar
  20. 20.
    Bacigalupo A, Lamparelli T, Bruzzi P, Guidi S, Alessandrino PE, di Bartolomeo P, et al. Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO). Blood. 2001;98:2942–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Baron F, Mohty M, Blaise D, Socie G, Labopin M, Esteve J, et al. Anti-thymocyte globulin as graft-versus-host disease prevention in the setting of allogeneic peripheral blood stem cell transplantation: a review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica. 2017;102:224–34.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR, et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med. 2012;367:1487–96.CrossRefPubMedGoogle Scholar
  23. 23.
    Lee SJ, Logan B, Westervelt P, Cutler C, Woolfrey A, Khan SP, et al. Comparison of patient-reported outcomes in 5-year survivors who received bone marrow vs peripheral blood unrelated donor transplantation: long-term follow-up of a randomized clinical trial. JAMA Oncol. 2016;2:1583–9.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    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.CrossRefPubMedGoogle Scholar

Copyright information

© Japanese Society of Hematology 2019

Authors and Affiliations

  • Shigeo Fuji
    • 1
    Email author
  • Koichi Miyamura
    • 2
  • Yoshinobu Kanda
    • 3
  • Takahiro Fukuda
    • 4
  • Takeshi Kobayashi
    • 5
  • Yukiyasu Ozawa
    • 2
  • Koji Iwato
    • 6
  • Naoyuki Uchida
    • 7
  • Tetsuya Eto
    • 8
  • Takashi Ashida
    • 9
  • Takehiko Mori
    • 10
  • Masashi Sawa
    • 11
  • Tatsuo Ichinohe
    • 12
  • Yoshiko Atsuta
    • 13
    • 14
  • Junya Kanda
    • 15
  • the HLA Working Group of the Japan Society for Hematopoietic Cell Transplantation
  1. 1.Department of HematologyOsaka International Cancer InstituteOsakaJapan
  2. 2.Department of HematologyJapanese Red Cross Nagoya First HospitalNagoyaJapan
  3. 3.Division of HematologySaitama Medical Center Jichi Medical UniversitySaitamaJapan
  4. 4.Department of Hematopoietic Stem Cell TransplantationNational Cancer Center HospitalTokyoJapan
  5. 5.Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases CenterKomagome HospitalTokyoJapan
  6. 6.Department of HematologyHiroshima Red Cross Hospital and Atomic-bomb Survivors HospitalHiroshimaJapan
  7. 7.Department of HematologyFederation of National Public Service Personnel Mutual Aid Associations Toranomon HospitalTokyoJapan
  8. 8.Department of HematologyHamanomachi HospitalFukuokaJapan
  9. 9.Division of Hematology and Rheumatology, Department of Internal MedicineKindai University Faculty of MedicineOsakaJapan
  10. 10.Division of Hematology, Department of MedicineKeio University School of MedicineTokyoJapan
  11. 11.Department of Hematology and OncologyAnjo Kosei HospitalNagoyaJapan
  12. 12.Department of Hematology and Oncology, Research Institute for Radiation Biology and MedicineHiroshima UniversityHiroshimaJapan
  13. 13.Japanese Data Center for Hematopoietic Cell TransplantationNagoyaJapan
  14. 14.Department of Healthcare AdministrationNagoya University Graduate School of MedicineNagoyaJapan
  15. 15.Department of Hematology and Oncology, Graduate School of MedicineKyoto UniversityKyotoJapan

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