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Coexistence of HLA and KIR ligand mismatches as a risk factor for viral infection early after cord blood transplantation

Bone Marrow Transplantation volume 57, pages 781–789 (2022)Cite this article

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Abstract

Viral infection is one of the lethal adverse events after cord blood transplantation (CBT). Human leukocyte antigen (HLA) and killer immunoglobulin-like receptor (KIR) ligand divergences can increase the risk of viral infection due to conflicting interactions between virus-infected cells and immune cells. However, the relationship between these disparities and the frequency of viral infection after CBT remains to be evaluated. Herein, we have conducted a retrospective multicenter study to assess the effect of HLA and KIR ligand mismatches on viral infections after CBT. The study included 429 patients, among which 126 viral infections occurred before day 100. Viral infection was significantly associated with poorer overall survival (OS; hazard ratio [HR] 1.74, p < 0.01). Patients harboring ≥3 mismatches in the HLA allele and inhibitory KIR ligand mismatches (HLA & KIR mismatches) had a significantly greater prevalence of viral infection (HR 1.66, p = 0.04). Thus, patients with HLA & KIR mismatches had poorer outcomes in terms of non-relapse mortality (HR 1.61, p = 0.05). Our study demonstrates the unfavorable impacts of HLA & KIR mismatches on viral infections and non-relapse mortality after CBT. Evaluating the viral infection risk and performance of an appropriate and early intervention in high-risk patients and optimizing the graft selection algorithm could improve the outcome of CBTs.

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Fig. 1: Workflow chart describing the patient inclusion and exclusion criteria.
Fig. 2: Prevalence and outcomes of post-CBT viral infection post-CBT.
Fig. 3: Effects of HLA & KIR mismatches on viral infection and grade II–IV aGVHD incidence.
Fig. 4: Effects of HLA & KIR mismatches on post-CBT outcomes.
Fig. 5: Conceptual diagrams of the impacts of HLA & KIR mismatches on post-CBT infection.

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Data availability statement

Raw data were created by KSCTG. Data supporting the study findings can be available from the corresponding author (YA) upon request.

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Acknowledgements

The authors would like to thank all the physicians and data managers at the participant centers who provided valuable transplantation data. We thank the KSCTG, including the Kyoto University Hospital, Kobe City Medical Center General Hospital, Japanese Red Cross Osaka Hospital, Kurashiki Central Hospital, Tenri Hospital, Kokura Memorial Hospital, Shizuoka General Hospital, Takatsuki Red Cross Hospital, Japanese Red Cross Wakayama Medical Center, Shinko Hospital, Kyoto City Hospital, Kitano Hospital, Japan Red Cross Otsu Hospital, Kyoto-Katsura Hospital, and Shizuoka Cancer Center. This study was supported in part by research funding from the Pfizer Competitive Grant Program, Japanese Society for Hematology, Japan Health Academy, Foundation for Promotion of Cancer Research, Lotte Foundation in Japan, and the Program for the Development of Next-generation Leading Scientists with Global Insight (L-INSIGHT), sponsored by the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan to YA.

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Authors and Affiliations

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

    Tomoki Iemura, Yasuyuki Arai, Toshio Kitawaki, Junya Kanda, Tadakazu Kondo, Takuto Mori, Kouhei Yamashita & Akifumi Takaori-Kondo

  2. Department of Clinical Laboratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Yasuyuki Arai

  3. Department of Hematology/Oncology, Kurashiki Central Hospital, Okayama, Japan

    Yasunori Ueda

  4. Department of Hematology, Kobe City Medical Center General Hospital, Hyogo, Japan

    Takuto Mori

  5. Department of Hematology, Japanese Red Cross Osaka Hospital, Osaka, Japan

    Kazunori Imada

  6. Department of Hematology, Kokura Memorial Hospital, Fukuoka, Japan

    Akihito Yonezawa

  7. Department of Hematology, Shizuoka General Hospital, Shizuoka, Japan

    Kazuhiro Yago

  8. Department of Hematology, Takatsuki Red Cross Hospital, Osaka, Japan

    Naoyuki Anzai

  9. Department of Hematology, Tenri Hospital, Nara, Japan

    Shinichi Kotani

  10. Deparment of Hematology, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan

    Masaharu Nohgawa

  11. Department of Hematology, Kitano Hospital, Osaka, Japan

    Toshiyuki Kitano

  12. Department of Hematology, Kyoto City Hospital, Kyoto, Japan

    Mitsuru Itoh

  13. Deparment of Hematology, Shinko Hospital, Hyogo, Japan

    Nobuyoshi Arima

  14. Department of Hematology, Kyoto-Katsura Hospital, Kyoto, Japan

    Toshinori Moriguchi

  15. Department of Hematology, Hyogo Prefectural Amagasaki General Medical Center, Hyogo, Japan

    Mitsumasa Watanabe

  16. Department of Hematology, Japan Red Cross Otsu Hospital, Shiga, Japan

    Masaaki Tsuji

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  1. Tomoki Iemura
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the Kyoto Stem Cell Transplantation Group (KSCTG)

  • Tomoki Iemura
  • , Yasuyuki Arai
  • , Toshio Kitawaki
  • , Junya Kanda
  • , Tadakazu Kondo
  • , Yasunori Ueda
  • , Takuto Mori
  • , Kazunori Imada
  • , Akihito Yonezawa
  • , Kazuhiro Yago
  • , Naoyuki Anzai
  • , Shinichi Kotani
  • , Masaharu Nohgawa
  • , Toshiyuki Kitano
  • , Mitsuru Itoh
  • , Nobuyoshi Arima
  • , Toshinori Moriguchi
  • , Mitsumasa Watanabe
  • , Masaaki Tsuji
  • , Kouhei Yamashita
  •  & Akifumi Takaori-Kondo

Contributions

TI and YA designed the study, reviewed and analyzed data, and wrote the paper; T Kitawaki, T Kondo, JK, YK, and AT-K interpreted data and revised the manuscript; YU, TM, KI, AY, KY, NA, SK, MN, T Kitano, MI, NA, TM, MW, and MT contributed to data collection and provided critiques on the manuscript.

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Correspondence to Yasuyuki Arai.

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Iemura, T., Arai, Y., Kitawaki, T. et al. Coexistence of HLA and KIR ligand mismatches as a risk factor for viral infection early after cord blood transplantation. Bone Marrow Transplant 57, 781–789 (2022). https://doi.org/10.1038/s41409-022-01621-w

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