急性移植片対宿主病における腸内真菌叢の役割の解明

2022 Fiscal Year Annual Research Report

• Project/Area Number: 20K08748
• Research Institution: The University of Tokyo
• Principal Investigator: 小沼 貴晶 東京大学, 医科学研究所, 准教授 (00709553)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 同酒造血細胞移植 / 常在真菌叢 / 腸内細菌叢 / 急性移植片対宿主病

Outline of Annual Research Achievements

同種造血細胞移植では、広域抗菌剤の投与による腸内細菌叢の変容が、全身の免疫担当細胞に影響を与えることで、同種免疫反応に起因する急性移植片対宿主病の発症に関与することが明らかとされている。同様に、同種造血細胞移植では抗真菌薬の投与により、常在真菌叢にもダイナミックな変容を引き起越すことで、同様に急性移植片対宿主病の発症に寄与している可能性はあるが、腸内真菌叢と急性移植片対宿主病との関連を明らかとされていない。本研究は、同種造血細胞移植における腸内真菌叢変容が全身の免疫担当細胞に与える影響と、それが急性移植片対宿主病の発症にどのような役割を果たしているのかを解明することを目的としている。今年度も、当院における同種造血細胞移植症例の糞便サンプルを収集して、糞便サンプルからDNAを抽出して、ITS1の保存領域に設計したユニバーサルプライマーを用いてPCRを行い、次世代シークエンサーを用いて解析を行った。同時に、同一糞便サンプルから抽出したDNAを用いて、16S領域を用いて腸内細菌叢も評価した。合計93症例の糞便のデータを得られた。現在、腸内真菌叢と腸内細菌叢との関連、末梢血各白血球サブセット、抗菌剤や抗真菌剤投与、急性移植片対宿主病や菌血症や真菌血症と腸内真菌叢との関連を解析している。今後は、マウスを用いた移植片対宿主病モデルにおいて、抗真菌薬投与と腸内真菌叢が免疫担当細胞に与える影響を評価することで、移植片対宿主病の予防や治療につながる可能性を検証していく予定である。

Research Products

• [Journal Article] Effect of Graft-versus-Host Disease on Post-Transplantation Outcomes following Single Cord Blood Transplantation Compared with Haploidentical Transplantation with Post-Transplantation Cyclophosphamide for Adult Acute Myeloid Leukemia (2023)
  • Author(s): Konuma T, Matsuda K, Shimomura Y, Tanoue S, Sugita J, Inamoto Y, Hirayama M, Ara T, Nakamae H, Ota S, Maruyama Y, Eto T, Uchida N, Tanaka M, Ishiwata K, Koi S, Takahashi S, Ozawa Y, Onizuka M, Kanda Y, Kimura T, Ichinohe T, Atsuta Y, Kanda J, Yanada M.
  • Journal Title: Transplantation and Cellular Therapy Volume: In Press Pages: In Press
  • DOI: 10.1016/j.jtct.2023.03.001
  • Peer Reviewed
• [Journal Article] Progress in survival following three decades of allogeneic hematopoietic cell transplantation for myelodysplastic syndrome: A real‐world registry study in Japan (2023)
  • Author(s): Konuma Takaaki、Itonaga Hidehiro、Ishiyama Ken、Hamamura Atsushi、Uchida Naoyuki、Ozawa Yukiyasu、Katayama Yuta、Sakurai Masatoshi、Ueda Yasunori、Matsuoka Ken‐ichi、Kawakita Toshiro、Eto Tetsuya、Ara Takahide、Kanda Junya、Onizuka Makoto、Fukuda Takahiro、Atsuta Yoshiko
  • Journal Title: American Journal of Hematology Volume: 98 Pages: E68-E71
  • DOI: 10.1002/ajh.26839
  • Peer Reviewed / Open Access
• [Journal Article] Thyrotoxicosis after unrelated cord blood transplantation for adults (2022)
  • Author(s): Konuma Takaaki、Tomonari Akira、Ooi Jun、Nagayama Hitomi、Kawakita Toshiro、Kato Seiko、Isobe Masamichi、Monna-Oiwa Maki、Tojo Arinobu、Nannya Yasuhito、Takahashi Satoshi
  • Journal Title: Annals of Hematology Volume: 102 Pages: 673～676
  • DOI: 10.1007/s00277-022-05068-3
  • Peer Reviewed
• [Journal Article] Conditioning regimens for allogeneic hematopoietic cell transplantation in acute myeloid leukemia: Real-world data from the Japanese registry studies (2022)
  • Author(s): Yanada Masamitsu、Harada Kaito、Shimomura Yoshimitsu、Arai Yasuyuki、Konuma Takaaki
  • Journal Title: Frontiers in Oncology Volume: 12 Pages: 1050633
  • DOI: 10.3389/fonc.2022.1050633
  • Peer Reviewed / Open Access
• [Journal Article] Genetic deletion and pharmacologic inhibition of E3 ubiquitin ligase HOIP impairs the propagation of myeloid leukemia (2022)
  • Author(s): Jimbo Koji、Hattori Ayuna、Koide Shuhei、Ito Takahiro、Sasaki Katsuhiro、Iwai Kazuhiro、Nannya Yasuhito、Iwama Atsushi、Tojo Arinobu、Konuma Takaaki
  • Journal Title: Leukemia Volume: 37 Pages: 122～133
  • DOI: 10.1038/s41375-022-01750-7
  • Peer Reviewed
• [Journal Article] Age and allogeneic hematopoietic cell transplantation outcomes in acute myeloid leukemia (2022)
  • Author(s): Yanada Masamitsu、Yamasaki Satoshi、Konuma Takaaki、Mizuno Shohei、Uchida Naoyuki、Onai Daishi、Fukuda Takahiro、Tanaka Masatsugu、Ozawa Yukiyasu、Eto Tetsuya、Ikegame Kazuhiro、Sawa Masashi、Katayama Yuta、Kawakita Toshiro、Onizuka Makoto、Kanda Yoshinobu、Ichinohe Tatsuo、Atsuta Yoshiko、Yano Shingo
  • Journal Title: International Journal of Hematology Volume: 117 Pages: 398～408
  • DOI: 10.1007/s12185-022-03486-7
  • Peer Reviewed
• [Journal Article] Comparison of transplant outcomes between haploidentical transplantation and single cord blood transplantation in non‐remission acute myeloid leukaemia: A nationwide retrospective study (2022)
  • Author(s): Matsuda K, Konuma T, Fuse K, Masuko M, Kawamura K, Hirayama M, Uchida N, Ikegame K, Wake A, Eto T, Doki N, Miyakoshi S, Tanaka M, Takahashi S, Onizuka M, Kato K, Kimura T, Ichinohe T, Takayama N, Kobayashi H, Nakamae H, Atsuta Y, Kanda J, Yanada M.
  • Journal Title: British Journal of Haematology Volume: 201 Pages: 106～113
  • DOI: 10.1111/bjh.18530
  • Peer Reviewed
• [Journal Article] Intensified conditioning regimens improved disease‐free survival and engraftment after unrelated single‐unit cord blood transplantation but not after matched sibling or matched unrelated donor allogeneic hematopoietic cell transplantation (2022)
  • Author(s): Konuma T, Kanda J, Uchida N, Nishijima A, Tanaka M, Ozawa Y, Sawa M, Onizuka M, Ota S, Maruyama Y, Kanda Y, Kawakita T, Ara T, Eto T, Nakamae H, Kimura T, Fukuda T, Atsuta Y; Donor/Source Working Group of theJapanese Society for Transplantation and Cellular Therapy.
  • Journal Title: Hematological Oncology Volume: 41 Pages: 147～158
  • DOI: 10.1002/hon.3094
  • Peer Reviewed
• [Journal Article] Salvage single-unit unrelated cord blood transplantation for graft failure following initial allogeneic transplantation in adult acute myeloid leukemia: trends in outcomes over the past 20 years (2022)
  • Author(s): Konuma T, Harada K, Kondo T, Masuko M, Uchida N, Yano S, Kawakita T, Onizuka M, Ota S, Sakaida E, Miyakoshi S, Ozawa Y, Imamura Y, Kimura T, Kanda Y, Fukuda T, Atsuta Y, Yanada M; Adult Acute Myeloid Leukemia Working Group of the Japanese Society for Transplantation and Cellular Therapy.
  • Journal Title: Bone Marrow Transplantation Volume: 57 Pages: 1848～1850
  • DOI: 10.1038/s41409-022-01840-1
  • Peer Reviewed
• [Journal Article] Haploidentical transplantation with post‐transplant cyclophosphamide versus single cord blood transplantation for myelodysplastic syndrome: A retrospective study from the Adult Myelodysplastic Syndrome Working Group of the Japanese Society for Transplantation and Cellular Therapy (JSTCT) (2022)
  • Author(s): Konuma Takaaki、Shimomura Yoshimitsu、Ishiyama Ken、Ara Takahide、Nakamae Hirohisa、Hiramoto Nobuhiro、Eto Tetsuya、Maruyama Yumiko、Nagafuji Koji、Ishikawa Jun、Uchida Naoyuki、Tanaka Masatsugu、Onizuka Makoto、Ueda Yasunori、Anzai Naoyuki、Kimura Takafumi、Kanda Yoshinobu、Fukuda Takahiro、Atsuta Yoshiko
  • Journal Title: American Journal of Hematology Volume: 97 Pages: E447-E450
  • DOI: 10.1002/ajh.26722
  • Peer Reviewed / Open Access
• [Journal Article] Higher Cryopreserved CD34+ Cell Dose Is Associated with Decreased Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Single-Unit Cord Blood Transplantation in Adults Given Prophylactic Ursodeoxycholic Acid and Intravenous Heparin (2022)
  • Author(s): Kato Seiko、Konuma Takaaki、Monna-Oiwa Maki、Isobe Masamichi、Takahashi Satoshi、Nannya Yasuhito
  • Journal Title: Transplantation and Cellular Therapy Volume: 28 Pages: 779.e1～779.e9
  • DOI: 10.1016/j.jtct.2022.08.013
  • Peer Reviewed
• [Journal Article] Reducing Mortality of Single-Unit Unrelated Cord Blood Transplantation for Relapsed Acute Myeloid Leukemia after a Previous Allogeneic Transplantation: A Real-World Retrospective Study Over the Past 19 Years in Japan (2022)
  • Author(s): Konuma Takaaki、Mizuno Shohei、Harada Kaito、Uchida Naoyuki、Takahashi Satoshi、Eto Tetsuya、Ota Shuichi、Kobayashi Hikaru、Katayama Yuta、Mori Yasuo、Maruyama Yumiko、Onizuka Makoto、Yonezawa Akihito、Kawakita Toshiro、Kimura Takafumi、Kanda Yoshinobu、Fukuda Takahiro、Atsuta Yoshiko、Yanada Masamitsu
  • Journal Title: Transplantation and Cellular Therapy Volume: 28 Pages: 777.e1～777.e11
  • DOI: 10.1016/j.jtct.2022.08.006
  • Peer Reviewed
• [Journal Article] Favorable Outcome with Conditioning Regimen of Flu/Bu4/Mel in Acute Myeloid Leukemia Patients in Remission Undergoing Cord Blood Transplantation (2022)
  • Author(s): Mizuno S, Takami A, Kawamura K, Shimomura Y, Arai Y, Konuma T, Ozawa Y, Sawa M, Ota S, Takahashi S, Anzai N, Hiramoto N, Onizuka M, Nakamae H, Tanaka M, Murata M, Kimura T, Kanda J, Fukuda T, Atsuta Y, Yanada M.
  • Journal Title: Transplantation and Cellular Therapy Volume: 28 Pages: 775.e1～775.e9
  • DOI: 10.1016/j.jtct.2022.07.026
  • Peer Reviewed
• [Journal Article] Prognostic impact of switching from cyclosporine to corticosteroids early after single cord blood transplantation (2022)
  • Author(s): Takano Kosuke、Konuma Takaaki、Monna-Oiwa Maki、Isobe Masamichi、Kato Seiko、Takahashi Satoshi、Nannya Yasuhito
  • Journal Title: Annals of Hematology Volume: 101 Pages: 2377～2378
  • DOI: 10.1007/s00277-022-04916-6
  • Peer Reviewed
• [Journal Article] Improved trends in survival and engraftment after single cord blood transplantation for adult acute myeloid leukemia (2022)
  • Author(s): Konuma T, Mizuno S, Kondo T, Arai Y, Uchida N, Takahashi S, Tanaka M, Kuriyama T, Miyakoshi S, Onizuka M, Ota S, Sugio Y, Kouzai Y, Kawakita T, Kobayashi H, Ozawa Y, Kimura T, Ichinohe T, Atsuta Y, Yanada M; Adult Acute Myeloid Leukemia Working Group of the Japanese Society for Transplantation and Cellular Therapy.
  • Journal Title: Blood Cancer Journal Volume: 12 Pages: 81
  • DOI: 10.1038/s41408-022-00678-6
  • Peer Reviewed / Open Access
• [Journal Article] Ideal Body Weight Is Useful For Predicting Neutrophil Engraftment and Platelet Recovery for Overweight and Obese Recipients in Single-Unit Cord Blood Transplantation (2022)
  • Author(s): Okada Yosuke、Nakasone Hideki、Konuma Takaaki、Uchida Naoyuki、Tanaka Masatsugu、Sugio Yasuhiro、Aotsuka Nobuyuki、Nishijima Akihiko、Katsuoka Yuna、Ara Takahide、Ota Shuichi、Onizuka Makoto、Sawa Masashi、Kimura Takafumi、Fukuda Takahiro、Atsuta Yoshiko、Kanda Junya、Kimura Fumihiko
  • Journal Title: Transplantation and Cellular Therapy Volume: 28 Pages: 504.e1～504.e7
  • DOI: 10.1016/j.jtct.2022.05.006
  • Peer Reviewed
• [Journal Article] Early prediction of neutrophil engraftment using manual leukocyte differential count after cord blood transplantation (2022)
  • Author(s): Mizukami Motoko、Konuma Takaaki、Nagai Etsuko、Monna‐Oiwa Maki、Isobe Masamichi、Kato Seiko、Takahashi Satoshi、Tojo Arinobu、Nannya Yasuhito
  • Journal Title: International Journal of Laboratory Hematology Volume: 44 Pages: e156-e159
  • DOI: 10.1111/ijlh.13803
  • Peer Reviewed
• [Presentation] 臍帯血移植の現状とユニット選択 (2023)
  • Author(s): 小沼貴晶
  • Organizer: 第45回 日本造血・免疫細胞療法学会総会
  • Invited
• [Presentation] 本邦における成人骨髄異形成症候群に対する同種造血細胞移植の年次推移 (2023)
  • Author(s): 小沼 貴晶、糸永 英弘、石山 謙、土岐 典子、内田 直之、小澤 幸泰、片山 雄太、片岡 圭亮、上田 恭典、 松岡 賢市、河北 敏郎、衛藤 徹也、荒 隆英、諫田 淳也、鬼塚 真仁、福田 隆浩、熱田 由子
  • Organizer: 第45回 日本造血・免疫細胞療法学会総会
• [Presentation] 臍帯血移植における強化前処置は無病生存率および生着率を改善する (2022)
  • Author(s): 小沼貴晶、諫田淳也、内田直之、西島曉彦、田中正嗣、小澤幸泰、澤正史、鬼塚真仁、太田秀一、 丸山ゆみ子、神田善伸、河北敏郎、荒隆英、衛藤徹也、中前博久、木村貴文、福田隆浩、熱田由子
  • Organizer: 第84回日本血液学会学術集会
• [Presentation] Japanese experience of single-unit cord blood transplantation for adults (2022)
  • Author(s): Takaaki Konuma
  • Organizer: 44th JSTCT Annual Meeting
  • Invited
• [Presentation] Tips on how to success CBT (2022)
  • Author(s): 小沼貴晶、山本久史
  • Organizer: 第44回 日本造血・免疫細胞療法学会総会
  • Invited