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Human leukocyte antigen (HLA) haplotype matching in unrelated single HLA allele mismatch bone marrow transplantation

Bone Marrow Transplantation volume 57, pages 407–415 (2022)Cite this article

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Abstract

The role of matching human leukocyte antigen (HLA) haplotypes in unrelated allogeneic bone marrow transplantation (allo-BMT) remains unclear. Here, we imputed the HLA haplotypes of 3657 patients who received unrelated single HLA allele-mismatched allo-BMT, included from the Transplant Registry Unified Management Program (TRUMP) database, the Japanese registry program for hematopoietic transplantation, using mathematical methods. We successfully imputed the HLA haplotypes of both patients and donors in 1365 cases (37.3%) with ≥90% probability. Of the patients, 1326 (97.1%) and 39 (2.9%) were categorized into one-haplotype-matched and no-haplotype-matched groups, respectively. Disease-free survival was significantly worse in the no-haplotype-matched group. Multivariate analyses revealed that no-haplotype-match was an independent risk factor for reducing disease-free survival (hazard ratio, 1.54 [95% confidence interval: 1.01–2.36]; p = 0.047). However, the overall survival did not significantly differ between the groups. The incidence of grade III–IV acute and chronic graft-versus-host disease did not significantly differ between the groups. Furthermore, there were no significant differences in the cumulative incidences of relapse and non-relapse mortality between the groups. Our findings suggest that imputing haplotypes using a mathematical approach can help to avoid transplanting patients with donors who do not share matching haplotypes, thereby improving the outcome of allo-BMT.

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Fig. 1: Algorithm used to impute individual HLA haplotypes.
Fig. 2: Disease-free survival and overall survival based on haplotype matching.
Fig. 3: Cumulative incidences of relapse and non-relapse mortality.
Fig. 4: Cumulative incidences of grade III–IV acute GVHD and chronic GVHD.
Fig. 5: Comparison of frequencies of the imputed haplotypes.

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Acknowledgements

The authors appreciate all physicians and data managers associated with the Japan Society for Hematopoietic Cell Transplantation. We thank the staff members of the Data Center of the Japan Society for Hematopoietic Cell Transplantation. We would also like to thank Editage (www.editage.com) for English language editing.

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Authors and Affiliations

  1. Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan

    Akihisa Kawajiri

  2. Department of Immune Regenerative Medicine, International Center for Cell and Gene Therapy, Research Promotion And Support Headquarters, Fujita Health University, Toyoake, Japan

    Takakazu Kawase

  3. HLA Foundation Laboratory, Kyoto, Japan

    Hidenori Tanaka

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

    Takahiro Fukuda

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

    Junichi Mukae

  6. Department of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital, Nagoya, Japan

    Yukiyasu Ozawa

  7. Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan

    Tetsuya Eto

  8. Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital, Tokyo, Japan

    Naoyuki Uchida

  9. Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan

    Takehiko Mori

  10. Department of Hematology, Tokyo Medical and Dental University, Tokyo, Japan

    Takehiko Mori

  11. Division of Hematology and Rheumatology, Department of Internal Medicine, Kindai University Hospital, Osakasayama, Japan

    Takashi Ashida

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

    Tadakazu Kondo & Junya Kanda

  13. Department of Hematology/Oncology, Tokai University School of Medicine, Isehara, Japan

    Makoto Onizuka

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

    Tatsuo Ichinohe

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

    Yoshiko Atsuta

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

    Yoshiko Atsuta

  17. Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan

    Satoko Morishima

Authors
  1. Akihisa Kawajiri
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Consortia

HLA Working Group of the Japan Society for Hematopoietic Cell Transplantation

  • Akihisa Kawajiri
  • , Takakazu Kawase
  • , Takashi Ashida
  • , Makoto Onizuka
  • , Tatsuo Ichinohe
  • , Yoshiko Atsuta
  • , Satoko Morishima
  •  & Junya Kanda

Contributions

AK designed the research, wrote the code of haplotype imputation tool, performed the statistical analysis, and analyzed the data. TK, HT, SM and JK analyzed and interpreted the data. TF, JM, YO, TE, NU, TM, TA, TK, MO, TI and YA gathered and organized the data. AK wrote the first draft, and all other authors contributed to the final version.

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Correspondence to Akihisa Kawajiri.

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Kawajiri, A., Kawase, T., Tanaka, H. et al. Human leukocyte antigen (HLA) haplotype matching in unrelated single HLA allele mismatch bone marrow transplantation. Bone Marrow Transplant 57, 407–415 (2022). https://doi.org/10.1038/s41409-021-01552-y

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