International prognostic algorithm for allogeneic stem cell transplantation by machine learning of comprehensive HLA and clinical information

• Project/Area Number: 21K08391
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kyoto University
• Principal Investigator: KANDA JUNYA 京都大学, 医学研究科, 講師 (30636311)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 同種造血幹細胞移植 / 臍帯血移植 / 機械学習 / 同種移植 / 造血幹細胞移植 / HLAエピトープ

Outline of Research at the Start

本研究では、HLA-DPB1, -DQB1 遺伝子座を含む未知のHLA アレルの測定・推測を行い、①患者・ドナー間のHLA適合度及び組み合わせの情報、②GVHDのターゲットとなり得る、HLAエピトープ及びHLA提示ペプチドのエピトープ情報、及び③詳細な臨床情報を含むレジストリーデータを、機械学習により解析することにより、網羅的な解析に基づく、GVHD など移植後予後因子のリスク評価のためのアルゴリズムを確立する。また、欧州の移植データも利用することで、欧米でも利用できる国際標準アルゴリズムを作成する。

Outline of Final Research Achievements

We conducted an analysis using the databases of the Japanese Society for Transplantation and Cell Therapy and Eurocord. In this study, we demonstrated the impact of T-cell epitope matching on graft-versus-host disease (GVHD) prevention strategies after HLA-mismatched related donor transplantation. Furthermore, regarding the mid- to long-term complications after allogeneic transplantation, we showed that incorporating events of acute GVHD improves the predictive ability of machine learning models. Additionally, we examined umbilical cord blood transplantation for malignant lymphoma in Japan and Europe, highlighting the importance of total body irradiation in transplantation for lymphoma while also noting the differences in the significance of HLA mismatch between Europe and Japan, suggesting the influence of ethnic differences.

Academic Significance and Societal Importance of the Research Achievements

本研究において、移植前因子のみならず移植後因子も含めることで、機械学習モデルの予測能が改善することが示されており、移植後因子も積極的に収集することの重要性が示されている。また、国際間でHLA不適合の影響は異なっており、集団の違いや危険因子を個別に分析することの重要性が示された。これらを考慮しながら同種移植の国際標準予後予測アルゴリズムの改善が必要である。。

Research Products

• [Int'l Joint Research] Eurocord(フランス)
• [Journal Article] Impact of stem cell selection between bone marrow and peripheral blood stem cells for unrelated hematopoietic stem cell transplantation for hematologic malignancies: on behalf of the Donor/Source Working Group of the Japanese Society for Transplantation and Cellular Therapy (2024)
  • Author(s): Hayashi H, Iwasaki M, Nakasone H, Tanoshima R, Shimabukuro M, Takeda W, Nishida T, Kako S, Fujiwara SI, Katayama Y, Sawa M, Serizawa K, Matsuoka KI, Uchida N, Ikeda T, Ohigashi H, Fukushima K, Hino M, Kanda Y, Fukuda T, Atsuta Y, Kanda J
  • Journal Title: Cytotherapy Volume: 26 Issue: 2 Pages: 178-184
  • DOI: 10.1016/j.jcyt.2023.11.012
• [Journal Article] Scoring system for optimal cord blood unit selection for single cord blood transplantation (2024)
  • Author(s): Watanabe Mizuki、Konuma Takaaki、Imahashi Nobuhiko、Terakura Seitaro、Kanda Junya et al.
  • Journal Title: Cytotherapy Volume: 26 Issue: 3 Pages: 286-298
  • DOI: 10.1016/j.jcyt.2023.12.001
  • Peer Reviewed
• [Journal Article] Cord blood transplantation for adult mature lymphoid neoplasms in Europe and Japan (2024)
  • Author(s): Watanabe M, Kanda J, Volt F, Ruggeri A, Suzuki R, Rafii H, Kimura F, Cappelli B, Kondo E, Scigliuolo GM, Takahashi S, et al.
  • Journal Title: Blood Advances Volume: 8 Issue: 3 Pages: 640-652
  • DOI: 10.1182/bloodadvances.2023010598
• [Journal Article] Impact of GVHD on lymphoma progression: Nationwide study from Japanese Society for Transplantation and Cellular Therapy (2023)
  • Author(s): Watanabe M, Kanda J, Fukuda T, Uchida N, Ikegame K, Kataoka K, Kobayashi H, Ara T, Ishikawa J, Matsuoka KI, Sugio Y, Nakazawa H, Ikeda T, Atsuta Y, Kondo E, Suzuki R
  • Journal Title: British Journal of Haematology Volume: 203 Issue: 3 Pages: 446-459
  • DOI: 10.1111/bjh.19041
  • Peer Reviewed
• [Journal Article] Mild Acute Graft-Versus-Host Disease Improves Outcomes After HLA-Haploidentical-Related Donor Transplantation Using Posttransplant Cyclophosphamide and Cord Blood Transplantation (2023)
  • Author(s): Wada F, Kanda J, Kamijo K, Nishikubo M, Yoshioka S, Ishikawa T, Ueda Y, Akasaka T, Arai Y, Izumi K, Hirata H, Ikeda T, Yonezawa A, Anzai N, Watanabe M, Imada K, Yago K, Tamura N, Itoh M, Masuo Y, Kunitomi A, Takeoka T, Kitano T, Arima N, Hishizawa M, Asagoe K, Kondo T, Takaori-Kondo A
  • Journal Title: Cell Transplantation Volume: 32
  • DOI: 10.1177/09636897231194497
  • Peer Reviewed / Open Access
• [Journal Article] Impact of HLA Epitope Matching on Outcomes After Unrelated Bone Marrow Transplantation (2022)
  • Author(s): Iwasaki Makoto、Kanda Junya、Tanaka Hidenori、Shindo Takero、Sato Takahiko、Doki Noriko、Fukuda Takahiro、Ozawa Yukiyasu、Eto Tetsuya、Uchida Naoyuki、Katayama Yuta、Kataoka Keisuke、Ara Takahide、Ota Shuichi、Onizuka Makoto、Kanda Yoshinobu、Ichinohe Tatsuo、Atsuta Yoshiko、Morishima Satoko
  • Journal Title: Frontiers in Immunology Volume: 13 Pages: 811733-811733
  • DOI: 10.3389/fimmu.2022.811733
  • Peer Reviewed / Open Access
• [Journal Article] The impact of GVHD on outcomes after adult single cord blood transplantation in European and Japanese populations (2021)
  • Author(s): Kanda Junya、Hayashi Hiromi、Ruggeri Annalisa、Kimura Fumihiko、Volt Fernanda、Takahashi Satoshi、et al.
  • Journal Title: Bone Marrow Transplantation Volume: 57 Issue: 1 Pages: 57-64
  • DOI: 10.1038/s41409-021-01479-4
• [Presentation] Development of a Stacked Ensemble Model for Risk Stratification of Chronic Gvhd after Allogeneic HSCT: Trump Cohort Study (2023)
  • Author(s): Iwasaki M, Kanda J, Kimura F, Seo S, Atsuta Y, Uchida N, Doki N, Fukuda T, Nishida T, Katayama Y, Tanaka M, Eto T, Ikegame K, Kanda Y, Sawa M, Onizuka M, Hino M, Ichinohe T, Tabuchi K, Takaori-Kondo A.
  • Organizer: the 65th ASH Annual Meeting and Exposition
  • Int'l Joint Research
• [Presentation] THE EFFECT OF HUMAN LEUKOCYTE ANTIGEN EPITOPE MATCHING ON OUTCOMES AFTER HAPLOIDENTICAL TRANSPLANTATION DEPENDS ON GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS AND PRETRANSPLANT DISEASE STATUS (2023)
  • Author(s): Iwasaki M, Kanda J, Tanaka H, Ikegame K, Doki N, Nakamae H, Eto T, Tanaka T, Ara T, Hiramoto N, Fukuda T, Ichinohe T, Atsuta Y, Morishima S.
  • Organizer: EBMT 49th Annual Meeting
  • Int'l Joint Research
• [Presentation] HLA class I抗体エピトープは、非血縁者間骨髄移植後における重症急性GVHD発症の増加と関連する (2021)
  • Author(s): 岩﨑惇、諫田淳也、田中秀則、進藤岳郎、土岐典子、福田隆浩、小澤幸泰、衛藤徹也、内田直之、片山雄太、片岡圭亮、鬼塚真仁、神田善伸、一戸辰夫、熱田由子、森島聡子
  • Organizer: 第29回日本組織適合性学会大会
• [Presentation] Impact of Human Leukocyte Antigen Epitope Matching on Outcomes after Unrelated Bone Marrow Transplantation (2021)
  • Author(s): Makoto Iwasaki, Junya Kanda, Hidenori Tanaka, Takero Shindo, Noriko Doki, Takahiro Fukuda, Yukiyasu Ozawa, Tetsuya Eto, Naoyuki Uchida, , Yuta Katayama, Keisuke Kataoka, Makoto Onizuka, Yoshinobu Kanda , Tatsuo Ichinohe, Yoshiko Atsuta,Satoko Morishima
  • Organizer: 63th ASH Annual Meeting
  • Int'l Joint Research
• [Remarks] 急性白血病治療における臍帯血移植後の合併症が及ぼす予後への影響
  • URL: https://www.kyoto-u.ac.jp/ja/research-news/2021-10-19-1