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HLA haploidentical stem cell transplantation from HLA homozygous donors to HLA heterozygous donors may have lower survival rates than haploidentical transplantation from HLA heterozygous donors to HLA heterozygous donors: a retrospective nationwide analysis

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Abstract

In HLA haploidentical stem cell transplantation, patients and donors usually share one HLA haplotype and have one different HLA haplotype (hetero-to-hetero). However, there are rare cases of transplantation from HLA homozygous donors to heterozygous recipients (homo-to-hetero), resulting in mismatches only in the graft-versus-host direction. We previously reported that homo-to-hetero transplants have a lower survival rate in a mouse model than hetero-to-hetero transplants due to stronger graft-versus-host disease (GVHD) but inferior graft-versus-leukemia effect. To examine whether homo-to-hetero transplant effects also occur in humans, we retrospectively compared the results of 59 homo-to-hetero and 4,539 hetero-to-hetero cases in the Japanese transplant registry data. The results showed no statistical difference between the homo-to-hetero and hetero-to-hetero groups in the cumulative incidences of neutrophil engraftment (83.1% vs 89.0%), acute GVHD II–IV (36.8% vs 38.8%), III–IV (16.8% vs 17.4%), chronic GVHD (32.7% vs 30.7%), relapse (52.9% vs 49.0%), and non-relapse mortality (31.6% vs 28.2%). In contrast, overall survival was significantly lower in the homo-to-hetero group than in the hetero-to-hetero group (12.6% vs 26.2%, p = 0.0308). The inferior effect of homo-to-hetero transplantation on overall survival remained significant in multivariate analyses.

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Data availability

The original data and protocols can be obtained upon reasonable request.

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Acknowledgements

We also thank all physicians, nurses, pharmacists, physical therapists, and support personnel for their care of the patients in this study.

Funding

This work was supported in part by Health and Labour Sciences Research Grants for Clinical Cancer Research from the Ministry of Health, Labour and Welfare, Japan, Grants-in aid for Scientific Research (21K08408).

Author information

Authors and Affiliations

  1. Department of Hematology, Hyogo Medical University Hospital, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan

    Keiko Fukunaga & Kazuhiro Ikegame

  2. Department of Hematology, Nippon Medical School, Tokyo, Japan

    Keiko Fukunaga

  3. Department of Hematology, Osaka Metropolitan University Hospital, Osaka, Japan

    Hirohisa Nakamae

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

    Noriko Doki

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

    Takahiro Fukuda

  6. Department of Hematology, Toyama Prefectural Central Hospital, Toyama, Japan

    Yukio Kondo

  7. Department of Hematology, Hokkaido University Hospital, Sapporo, Japan

    Takahide Ara

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

    Tetsuya Eto

  9. Hematology, Oncology and Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Japan

    Yasuo Mori

  10. Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan

    Ken-ichi Matsuoka

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

    Yoshinobu Kanda

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

    Makoto Onizuka

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

    Yoshiko Atsuta

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

    Tatsuo Ichinohe

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

    Satoko Morishima

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

    Junya Kanda

Authors
  1. Keiko Fukunaga
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  2. Kazuhiro Ikegame
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  3. Hirohisa Nakamae
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  4. Noriko Doki
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  5. Takahiro Fukuda
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  15. Satoko Morishima
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  16. Junya Kanda
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Consortia

JSTCT HLA Working Group

Contributions

KI designed the study, advised on the methods, and revised the manuscript. KF and KI wrote the manuscript. HN, ND, TF, KY, TA, TE, YM, KM, YK, MO collected data and revised the manuscript. YA and TI managed the unified registry database and revised the manuscript. SM and JK edited the paper and was responsible for the project of the JSTCT HLA Working Group.

Corresponding author

Correspondence to Kazuhiro Ikegame.

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There are no conflicts of interest to report associated with this study.

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Fukunaga, K., Ikegame, K., Nakamae, H. et al. HLA haploidentical stem cell transplantation from HLA homozygous donors to HLA heterozygous donors may have lower survival rates than haploidentical transplantation from HLA heterozygous donors to HLA heterozygous donors: a retrospective nationwide analysis. Int J Hematol 119, 173–182 (2024). https://doi.org/10.1007/s12185-023-03693-w

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  • DOI: https://doi.org/10.1007/s12185-023-03693-w

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