Effects of HLA mismatch on cytomegalovirus reactivation in cord blood transplantation


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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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.

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Correspondence to Hisayuki Yokoyama.

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