Abstract

Although human leukocyte antigen (HLA) mismatch is often thought to be associated with a high incidence of cytomegalovirus (CMV) reactivation, it is not clear whether this process is mediated by HLA mismatch or other factors, such as acute graft-versus-host disease (aGVHD). Here we focused on cord blood transplantation (CBT) and examined the effects of HLA mismatch on the incidence of CMV reactivation while minimizing the effects of aGVHD. In a multivariate analysis considering aGVHD as a time-dependent covariate, a significant effect on the incidence of CMV reactivation was noted for HLA disparity (hazard ratio [HR]: 0.54 for 8/8 match compared with 3-allele mismatch) and development of aGVHD (HR: 1.26). Next, in an analysis excluding cases that developed aGVHD, the incidences of CMV reactivation for 8/8 match and 1-allele mismatch were low compared with those for other mismatches. These findings were supported by the multivariate analysis (HR: 0.49 for 8/8 match and 0.64 for 1-allele mismatch compared with 3-allele mismatch). Together, these results suggested that HLA mismatch was involved in CMV reactivation and was associated with high morbidity of opportunistic infection after CBT.

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Acknowledgements

The authors would like to thank all the physicians and data managers who contributed valuable data to the Japan Society for Hematopoietic Cell Transplantation (JSHCT). The authors also would like to thank the staff members of the Data Center of JSHCT for their contributions.

HLA Working Group of the Japan Society for Hematopoietic Cell Transplantation:

Junya Kanda, Yoshiko Atsuta, Kazuhiro Ikegame, Tatsuo Ichinohe, Atae Utsunomiya, Makoto Onizuka, Shunichi Kato, Takakazu Kawase, Yoshinobu Kanda, Sung-Won Kim, Yachiyo Kuwatsuka, Takeshi Kobayashi, Yoshifusa Takatsuka, Yoshiyuki Takahashi, Junji Tanaka, Hiroya Tamaki, Masanori Tsuji, Tetsuya Nishida, Yoshinobu Maeda, Masayoshi Masuko, Ryosuke Matsuno, Makoto Murata, Satoko Morishima, Yasuo Morishima, Hisayuki Yokoyama, Atsushi Wake, Nobuhiro Watanabe, T Ashida, Minoko Takanashi, Takumi Hoshino, Toshio Yabe, Kana Sakamoto, Shigeo Fuji, Koichi Miyamura, Nobuyoshi Arima, Eisei Kondo, Makoto Yoshimitsu, Koji Kawamura, Takahito Kawata, Kenji Kishimoto, Raine Tatara, Takeshi Hagino, Shin-Ichiro Fujiwara, Yoshimitsu Shimomura, Hirotoshi Sakaguchi, Shigeki Hirabayashi, Hiroto Ishii, Yoshiyuki Onda, Itaru Kato, Akihisa Kawajiri, Takero Shindo, Masahito Tokunaga, Atsushi Nonami, Hiroyuki Muranushi, Noriyoshi Yoshinaga, Naomi Kawashima, Souichi Shiratori, Yuma Tada, Susumu Tanoue, Masahiro Hirayama, Keiko Fukunaga, Marie Ohbiki.

Author information

Affiliations

  1. Department of Hematology, Sendai Medical Center, National Hospital Organization, Sendai, Japan

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

    • Junya Kanda
  3. Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, Isehara, Japan

    • Shunichi Kato
  4. Department of Hematology, Kawasaki Medical School, Kurashiki, Japan

    • Eisei Kondo
  5. Department of Hematology and Oncology, Okayama University, Okayama, Japan

    • Yoshinobu Maeda
  6. HLA Laboratory, Kyoto, Japan

    • Hiroo Saji
  7. Division of Molecular Therapy, The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    • Satoshi Takahashi
  8. Department of Hematology/Oncology, Tokai University School of Medicine, Isehara, Japan

    • Makoto Onizuka
  9. Department of Hematology and Rheumatology, Tohoku University Hospital, Sendai, Japan

    • Yasushi Onishi
  10. Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    • Yukiyasu Ozawa
  11. Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan

    • Heiwa Kanamori
  12. Department of Hematology, Osaka International Cancer Institute, Osaka, Japan

    • Jun Ishikawa
  13. Department of Internal Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan

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

    • Tatsuo Ichinohe
  15. Blood Service Headquarters, Japanese Red Cross Society, Tokyo, Japan

    • Minoko Takanashi
  16. Department of Hematology and Oncology, Children’s Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    • Koji Kato
  17. Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan

    • Yoshiko Atsuta
  18. Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan

    • Yoshiko Atsuta
  19. Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan

    • Yoshinobu Kanda
  20. Division of Hematology, Department of Medicine, Jichi Medical University, Shimotsuke, Japan

    • Yoshinobu Kanda

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    The authors declare that they have no conflict of interest.

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    Correspondence to Hisayuki Yokoyama.

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    https://doi.org/10.1038/s41409-018-0369-0