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Histocompatibility and Donor Selection Issues

Impact of the presence of HLA 1-locus mismatch and the use of low-dose antithymocyte globulin in unrelated bone marrow transplantation

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Abstract

HLA 1-locus-mismatched unrelated donors (1MMUD) have been used in allogeneic hematopoietic stem cell transplantation (allo-HCT) for patients who lack an HLA-matched donor. We retrospectively analyzed 3313 patients with acute leukemia or myelodysplastic syndrome who underwent bone marrow transplantation from an HLA allele-matched unrelated donor (MUD) or 1MMUD between 2009 and 2014. We compared the outcomes of MUD (n=2089) and 1MMUD with antithymocyte globulin (ATG) (1MM-ATG(+); n=109) with those of 1MMUD without ATG (1MM-ATG(−); n=1115). The median total dose of ATG (thymoglobulin) was 2.5 mg/kg (range 1.0–11.0 mg/kg) in the 1MM-ATG(+) group. The rates of grade III–IV acute GvHD, non-relapse mortality (NRM) and overall mortality were significantly lower in the MUD group than in the 1MM-ATG(−) group (hazard ratio (HR) 0.77, P=0.016; HR 0.74; P<0.001; and HR 0.87, P=0.020, respectively). Likewise, the rates of grade III–IV acute GVHD, NRM and overall mortality were significantly lower in the 1MM-ATG(+) group than in the 1MM-ATG(−) group (HR 0.42, P=0.035; HR 0.35, P<0.001; and HR 0.71, P=0.042, respectively). The outcome of allo-HCT from 1MM-ATG(−) was inferior to that of allo-HCT from MUD even in the recent cohort. However, the negative impact of 1MMUD disappeared with the use of low-dose ATG without increasing the risk of relapse.

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Acknowledgements

We thank all of the physicians and staff members of the collaborating institutes of the Japan Society for Hematopoietic Stem Cell Transplantation.

Author contributions

KK, JK and YK designed the study and performed the statistical analysis; KK, JK, SF, MM, K Ikegame and YK interpreted the data and wrote the manuscript; KY, TF, TH, YO, NU, YK, K Iwato, TS, MH and HH provided the patient data; TF, TI and YA collected the patient data; and all of the authors interpreted the data, and reviewed and approved the final manuscript.

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Authors and Affiliations

  1. Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan

    K Kawamura & Y Kanda

  2. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    J Kanda

  3. Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan

    S Fuji & T Fukuda

  4. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    M Murata

  5. Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan

    K Ikegame

  6. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    K Yoshioka

  7. Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Y Ozawa

  8. Department of Hematology, Toranomon Hospital, Tokyo, Japan

    N Uchida

  9. Department of Blood Transfusion, Hiroshima Red Cross and Atomic Bomb Survivors Hospital, Hiroshima, Japan

    K Iwato

  10. Leukemia Research Center, Saiseikai Maebashi Hospital, Gunma, Japan

    T Sakura

  11. Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan

    M Hidaka

  12. Department of Hematology/Division of Stem Cell Transplantation, Kobe General Hospital/Institute of Biomedical Research and Innovation, Kobe, Japan

    H Hashimoto

  13. Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

    T Ichinohe

  14. Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan

    Y Atsuta

  15. Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Y Atsuta

  16. Division of Hematology, Department of Medicine, Jichi Medical University, Shimotsuke, Japan

    Y Kanda

Authors
  1. K Kawamura
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  2. J Kanda
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  4. M Murata
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  5. K Ikegame
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  6. K Yoshioka
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  7. T Fukuda
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  8. Y Ozawa
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  9. N Uchida
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  10. K Iwato
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  11. T Sakura
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  12. M Hidaka
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  13. H Hashimoto
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  14. T Ichinohe
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  15. Y Atsuta
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  16. Y Kanda
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Correspondence to Y Kanda.

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Kawamura, K., Kanda, J., Fuji, S. 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 Transplant 52, 1390–1398 (2017). https://doi.org/10.1038/bmt.2017.153

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