Machine Learning Prognostic Models for Acute Leukemia and Decision Making Tools for Clinical Practice and Patients.

• Project/Area Number: 19K16975
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Niigata University
• Principal Investigator: Fuse Kyoko 新潟大学, 医歯学総合病院, 講師 (40783329)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 急性白血病 / 予後因子 / 機械学習 / 急性骨髄性白血病 / 医療費 / 治療方針決定ツール / 意思決定補助 / 予測モデル / 個別化医療

Outline of Research at the Start

急性白血病は小児から高齢者まで幅広い年齢層に発症する難治性疾患で、若年者では標準的化学療法や造血幹細胞移植、高齢者では減弱した治療や支持療法を行う。最近は新薬の開発と導入も進み、治療選択肢は増え、また患者ごとの背景も多様である。複数の因子を総合的に判断し患者毎に治療をカスタマイズするような個別化医療が可能となれば、急性白血病の予後はさらに改善できると考える。
本研究では、急性白血病患者の疾患背景、診療・患者情報をもとに機械学習で経過予測モデルの作成と治療の成功パターン検出を行う。この成果により担当医の診療補助や患者の自己決定の補助として有用なツールの開発を目指す。

Outline of Final Research Achievements

We attempted to create a predictive model for the course of acute leukemia patients in order to synthesize multiple prognostic factors and customize treatment for each patient. First, we searched for novel prognostic factors to create the model. We identified the Marker chromosome as the molecular background of the disease, WT-1 mRNA expression thresholds, intensive oral care as supportive care to prevent complications, and HLA gene polymorphisms involved in tumor immune response.It was pointed out that the ADTree program has the potential to improve prognosis by changing the transplant source according to disease and stage prior to HSCT, and that preventive intervention may be possible by predicting the frequency of graft-versus-host disease.

Academic Significance and Societal Importance of the Research Achievements

機械学習による予後予測モデルで治療成功のための分岐点を抽出する可能性を明らかにできた。今後の個別化医療に応用が期待でいる。機械学習の精度を高めるためには、診療記録・データの質とばらつき、解析データの量などが今後の課題と考えられる。今後は、特に予備能が低い高齢者において治療選択と予後、医療費への影響に関する個別経過予測モデルの構築を試みたい。

Research Products

• [Journal Article] Comparison of transplant outcomes between haploidentical transplantation and single cord blood transplantation in non‐remission acute myeloid leukaemia: A nationwide retrospective study (2023)
  • Author(s): K Matsuda , T Konuma , K Fuse , M Masuko , K Kawamura , M Hirayama , N Uchida , K Ikegame , A Wake , T Eto , N Doki , S Miyakoshi , M Tanaka , S Takahashi , M Onizuka , K Kato , T Kimura , T Ichinohe , N Takayama , H Kobayashi , H Nakamae , Y Atsuta , J Kanda , M Yanada
  • Journal Title: British Journal of Haematology Volume: 201 Issue: 1 Pages: 106-113
  • DOI: 10.1111/bjh.18530
  • Peer Reviewed / Open Access
• [Journal Article] Intensive oral care can reduce bloodstream infection with coagulase-negative staphylococci after neutrophil engraftment in allogeneic hematopoietic stem-cell transplantation (2021)
  • Author(s): Suwabe Tatsuya、Fuse Kyoko、Katsura Kouji、Soga Marie、Katagiri Takayuki、Shibasaki Yasuhiko、Narita Miwako、Sone Hirohito、Masuko Masayoshi
  • Journal Title: Supportive Care in Cancer Volume: 30 Issue: 1 Pages: 475-485
  • DOI: 10.1007/s00520-021-06447-8
  • Peer Reviewed
• [Journal Article] WT1-specific CD8+ cytotoxic T cells with the capacity for antigen-specific expansion accumulate in the bone marrow in MDS. (2021)
  • Author(s): Tatsuya Suwabe, Yasuhiko Shibasaki, Hiroyuki Sato, Suguru Tamura, Takayuki Katagiri, Hiroki Nemoto, Takuya Kasami, Takashi Kozakai, Ayako Nanba, Toshiki Kitajima, Kyoko Fuse, Takashi Ushiki, Hirohito Sone, Miwako Narita, Masayoshi Masuko
  • Journal Title: International journal of hematology Volume: 113 Issue: 5 Pages: 723-734
  • DOI: 10.1007/s12185-021-03083-0
  • Peer Reviewed
• [Journal Article] Marker chromosome is a strong poor prognosis factor after allogeneic HSCT for adverse‐risk AML patients (2020)
  • Author(s): Fuse Kyoko、Tanaka Tomoyuki、Shibasaki Yasuhiko、Furukawa Tatsuo、Narita Miwako、Sone Hirohito、Masuko Masayoshi
  • Journal Title: European Journal of Haematology Volume: 105 Issue: 5 Pages: 616-625
  • DOI: 10.1111/ejh.13495
  • Peer Reviewed / Open Access
• [Journal Article] The Glasgow prognostic score divides high-risk hematopoietic cell transplantation-specific comorbidity index patients into stratified subgroups in allogeneic hematopoietic cell transplantation (2020)
  • Author(s): Shibasaki Yasuhiko、Suwabe Tatsuya、Katagiri Takayuki、Fuse Kyoko、Narita Miwako、Sone Hirohito、Masuko Masayoshi
  • Journal Title: Annals of Hematology Volume: 99 Issue: 3 Pages: 671-673
  • DOI: 10.1007/s00277-020-03936-4
  • Peer Reviewed
• [Journal Article] Hypertrophic pachymeningitis associated withmyelodysplastic syndrome. (2020)
  • Author(s): Kaihatsu A, Fuse K, Sone H, Masuko M.
  • Journal Title: eJHaem Volume: 1 Pages: 12-13
  • Peer Reviewed / Open Access
• [Journal Article] Patient-based Prediction Algorithm of Relapse After allo-HSCT for Acute Leukemia and Its Usefulness in the Decision-Making Process Using a Machine Learning Approach (2019)
  • Author(s): Fuse K, Uemura S, Tamura S, Suwabe T, Katagiri T, Tanaka T, Ushiki T, Shibasaki Y, Sato N, Yano T, Kuroha T, Hashimoto S, Furukawa T, Narita M, Sone H, Masuko M.
  • Journal Title: Cancer Med. Volume: Sep;8(11) Issue: 11 Pages: 5058-5067
  • DOI: 10.1002/cam4.2401
  • Peer Reviewed / Open Access
• [Journal Article] Using a machine learning algorithm to predict acute graft-versus-host disease following allogeneic transplantation. (2019)
  • Author(s): Arai Y, Kondo T, Fuse K, Shibasaki Y, Masuko M, Sugita J, Teshima T, Uchida N, Fukuda T, Kakihana K, Ozawa Y, Eto T, Tanaka M, Ikegame K, Mori T, Iwato K, Ichinohe T, Kanda Y, Atsuta Y.
  • Journal Title: Blood Adv. Volume: 3(22) Issue: 22 Pages: 3626-3634
  • DOI: 10.1182/bloodadvances.2019000934
  • NAID: 120006817456
  • Peer Reviewed / Open Access
• [Presentation] HLA-B Leader Mismatch Positively Correlates with Survival Rate in Haplo and Cord Blood Transplantation for Acute Leukemia in Japanese Patients. (2022)
  • Author(s): Katagiri T, Suwabe T, Fuse K, Shibasaki Y, Sone H, Masuko M.
  • Organizer: 64th ASH Annual Meeting and Exposition.
  • Int'l Joint Research
• [Presentation] Breadth of the Human Leukocyte Antigens Class I Immunopeptidome in Allogenic Hematopoietic Stem Cell Transplantation Outcomes for Myeloid Malignancy (2022)
  • Author(s): Fuse K, Suwabe T, Katagiri T, Shibasaki Y, Sone H, Masuko M.
  • Organizer: 64th ASH Annual Meeting and Exposition.
  • Int'l Joint Research
• [Presentation] EASIX ASSESSED AT 1 YEAR AFTER ALLOGENIC HEMATOPOIETIC CELL TRANSPLANTATION PREDICTS THE ONSET OF SUBSEQUENT NON-RELAPSE MORTALITY. (2022)
  • Author(s): Takeda R, Shibasaki Y, Katagiri T, Fuse K, Sone H, Masuko M
  • Organizer: European Hematology Association 2022
  • Int'l Joint Research
• [Presentation] Association of HLA class I evolutionary divergence and outcome of allo-HCT for myeloid malignancy. (2022)
  • Author(s): 布施香子、諏訪部達也、片桐隆幸、柴崎康彦、曽根博仁、増子正義.
  • Organizer: 第84回日本血液学会学術集会
• [Presentation] 同種造血幹細胞移植後の腹水の臨床経過：単一施設での解析 (2022)
  • Author(s): 土田拓睦、布施香子、古山悠里、武田ルイ、米沢穂高、田村秀、片桐隆幸、柴崎康彦、瀧澤淳、曽根博仁、増子正義.
  • Organizer: 第44回日本造血・免疫細胞療法学会総会.
• [Presentation] Stratification of Intermediate-Risk Acute Myeloid Leukemia According to the Expression Level of WT1 mRNA at Diagnosis. (2021)
  • Author(s): Fuse K, Kaihatsu A, Kitajima T, Momoi A, Kasami T, Katagiri T, Shibasaki Y, Furukawa T, Narita M, Sone H, Masuko M.
  • Organizer: 第63回米国血液学会総会
  • Int'l Joint Research
• [Presentation] The Diversity of Long-Term Persistent WT1-Specific Cytotoxic T Lymphocytes after Wilms’ Tumor 1 Peptide Vaccination. (2021)
  • Author(s): Suwabe T, Shibasaki S, Tamura S, Katagiri T, Fuse F, Ushiki T, Sone H, Narita M, Masuko M.
  • Organizer: 第63回米国血液学会総会
  • Int'l Joint Research
• [Presentation] 診断時WT1mRNA高発現は中間リスクAMLの予後良好因子である (2021)
  • Author(s): 布施 香子、海發 茜、外山 夢乃、相良 文太、北嶋 俊樹、桃井 明仁、笠見 卓哉、根本 洋樹、片桐 隆幸、柴崎 康彦、古川 達雄、成田 美和子、曽根 博仁、増子 正義
  • Organizer: 第83回日本血液学会学術集会
• [Presentation] 初回寛解導入不能期と再発後非寛解期における急性骨髄性白血病に対する同種造血幹細胞移植の比較 (2021)
  • Author(s): 布施 香子、武田 ルイ、水戸部正樹、米沢 穂高、諏訪部達也、片桐 隆幸、柴崎 康彦、曽根 博仁、増子 正義
  • Organizer: 第43回日本造血細胞移植学会総会
• [Presentation] EASIX-1 year as the predictors in late non-relapse mortality after allogenic-HCT (2021)
  • Author(s): 武田るい, 柴崎康彦, 本宮奈津子, 片桐隆幸, 布施香子, 曽根博仁, 増子正義
  • Organizer: 第83回日本血液学会学術集会
• [Presentation] Post-transplant relapse of AML within one year is associated with a high mortality rate (2021)
  • Author(s): 片桐隆幸, 本宮奈津子, 武田ルイ, 水戸部正樹, 米沢穂高, 諏訪部達也, 布施香子, 柴崎康彦, 瀧澤淳, 曽根博仁, 増子正義
  • Organizer: 第83回日本血液学会学術集会
• [Presentation] Persistence and diversity of WT1-specific CTLs in a CML patient vaccinated WT1 peptide (2021)
  • Author(s): 諏訪部達也, 柴崎康彦, 田村秀, 片桐隆幸, 布施香子, 牛木隆志, 曽根博仁, 成田美和子, 増子正義
  • Organizer: 第83回日本血液学会学術集会
• [Presentation] Genetic manipulation resulting in decreased donor chondroitin sulfate mitigates GVHD in mice (2021)
  • Author(s): 田村秀、牛木隆志、諏訪部達也、片桐隆幸、布施香子、柴崎康彦、遠藤岳郎、五十嵐道弘、曽根博仁、増子正義
  • Organizer: 第83回日本血液学会学術集会
• [Presentation] 単一施設におけるATGとPTCYを用いた半合致移植の臨床成績の比較 (2021)
  • Author(s): 米沢穂高, 柴崎康彦, 武田ルイ, 片桐隆幸, 布施香子, 成田美和子, 曽根博仁, 増子正義
  • Organizer: 日本造血細胞移植学会総会
• [Presentation] イノツズマブによる再寛解導入に引き続いてブリナツモマブを投与し再移植できた B-ALL の 1 例 (2021)
  • Author(s): 米沢穂高、布施香子、片桐隆幸、柴崎康彦、瀧澤淳、曽根博仁、増子正義
  • Organizer: 第15回 日本血液学会関東甲信越地方会
• [Presentation] Significance of Marker Chromosome on the Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for AML. (2020)
  • Author(s): Fuse K, Masuko M, Mizuno S, Harada K, Uchida N, Doki N, Fukuda T, Tanaka M, Ozawa Y, Ikegame K, Eto T, Kanda Y, Ichinohe T, Atsuta Y, Yanada M.
  • Organizer: 62nd ASH Annual Meeting and Exposition
  • Int'l Joint Research
• [Presentation] Genetic Manipulation Resulting in Decreased Donor Chondroitin sulfate Synthesis Mitigates GVHD Following Allogeneic Hematopoietic Cell Transplantation in a Murine Model. (2020)
  • Author(s): Tamura S, Ushiki T, Suwabe T, Katagiri T, Tanaka T, Fuse K, Shibasaki Y, Narita M, Igarashi M, Sone H, Masuko M.
  • Organizer: 62nd ASH Annual Meeting and Exposition
  • Int'l Joint Research
• [Presentation] 急性骨髄性白血病の移植成績に及ぼすマーカー染色体の意義. (2020)
  • Author(s): 布施香子、増子正義、水野昌平、原田介、斗内田直之、土岐典子、福田隆浩、田中正嗣、小澤幸泰、池亀和博、衛藤徹也、神田善伸、一戸辰夫、熱田由子、柳田正光
  • Organizer: 第82回日本血液学会学術集会.
• [Presentation] 機能的なWT1特異的CD8陽性T細胞クローンは骨髄異形成症候群の骨髄内に集積する. (2020)
  • Author(s): 諏訪部達也、柴崎康彦、佐藤廣幸、田村秀、片桐隆幸、根本洋樹、笠見卓哉、小堺貴司、難波亜矢子、北嶋俊樹、布施香子、牛木隆志、曽根博仁、成田美和子、増子正義.
  • Organizer: 第82回日本血液学会学術集会.
• [Presentation] FOXOs下流因子を対象とした白血病幹細胞の分化誘導法の開発. (2020)
  • Author(s): 倉吉健太、上野将也、高瀬雄介、布施香子、太田久美子、田所優子、平尾敦.
  • Organizer: 第82回日本血液学会学術集会.
• [Presentation] MDS-EB2に対し、ATG併用GVHD 予防法を用いたHLAクラスI遺伝子型2座不適合非血縁者間骨髄移植を施行した1例 (2020)
  • Author(s): 沢穂高、柴崎康彦、笠見卓也、鈴木隆晴、田村秀、河本啓介、布施香子、瀧澤淳、曽根博仁、増子正義.
  • Organizer: 第42回日本造血細胞移植学会総会
• [Presentation] Depletion of Pre-Transplant Skeletal Muscle Is Significant Poor Prognostic Factor in Allogeneic Hematopoietic Cell Transplantation. (2019)
  • Author(s): Shibasaki Y, Kobayashi K, Suwabe T, Fuse K, Narita M, Sone H, Masuko M.
  • Organizer: 61st American Society of Hematology (ASH) Annual Meeting and Exposition.
  • Int'l Joint Research
• [Presentation] INTENSIVE ORAL CARE CAN REDUCE BLOOD STREAM INFECTION POST NEUTROPHIL ENGRAFTMENT IN ALLOGENEIC HSCT. (2019)
  • Author(s): Suwabe T, Fuse K, Katsura K, Tanaka K, Tamura S, Katairi T, Tanaka T, Ushiki T, Shibasaki Y, Narita M, Sone H, Masuko M.
  • Organizer: The 24th EHA (European Hematology Association) Congress.
  • Int'l Joint Research
• [Presentation] MARKER CHROMOSOME IS A STRONG POOR PROGNOSIS FACTOR AFTER ALLOGENEIC HSCT FOR AML PATIENTS. (2019)
  • Author(s): Fuse K, Tanaka T, Uemura S, Tamura S, Suwabe T, Katagiri T, Ushiki T, Shibasaki Y, Satou N, Yano T, Kuroha T, Hashimoto S, Furukawa T, Narita M, Sone H, Masuko M.
  • Organizer: The 24th EHA (European Hematology Association) Congress.
  • Int'l Joint Research
• [Presentation] Monitoring of Persistent CTLs over 10 Years Using MLPC after WT1 Peptide Vaccine in a CML Patient. (2019)
  • Author(s): Suwabe T, Ogawa S, Goto W, Sato H, Fuse K, Shibasaki Y, Sone H, Masuko M, Narita M.
  • Organizer: The 10th JSH International Symposium.
  • Int'l Joint Research
• [Presentation] 同種造血幹細胞移植後の予後予測におけるaugmented HCT-CIの有用性. (2019)
  • Author(s): 海發茜、柴崎康彦、田村秀、片桐隆幸、河本啓介、難波亜矢子、布施香子、成田美和子、曽根博仁、増子正義.
  • Organizer: 第81回日本血液内科学会学術集会.
• [Presentation] 造血幹細胞再移植例におけるNRMのリスク因子. (2019)
  • Author(s): 田村秀、布施香子、海發茜、片桐隆幸、河本啓介、難波亜矢子、柴崎康彦、成田美和子、曽根博仁、増子正義.
  • Organizer: 第81回日本血液内科学会学術集会.
• [Presentation] 同種造血幹細胞移植後の白血病再発例の臨床的検討. (2019)
  • Author(s): 藤井壮人、布施香子、柴崎康彦、曽根博仁、増子正義.
  • Organizer: 日本内科学会
• [Presentation] 同種造血細胞移植前の骨格筋量は予後予測に有用である. (2019)
  • Author(s): 永井千楓、柴崎康彦、布施香子、増子正義、曽根博仁.
  • Organizer: 日本内科学会
• [Presentation] 同種造血幹細胞移植後に再発した急性白血病の全生存と TRM の予後因子の検討 Overall Survival and Therapy-related Mortality of Relapsed Acute Leukemia after Allo-HSCT. (2019)
  • Author(s): 布施香子、諏訪部達也、片桐隆幸、柴崎康彦、成田美和子、曽根博仁、増子正義.
  • Organizer: 第41回日本造血細胞移植学会総会.
• [Book] わかりやすい疾患と処方薬の解説【病態・薬物治療編】 (2022)
  • Author(s): 編集「わかりやすい疾患と処方薬の解説」編集企画委員会
  • Total Pages: 783
  • Publisher: アークメディア