Antigen positive blood transfusion for patients having irregular antibodies

• Project/Area Number: 16K08933
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Takeshita Akihiro 浜松医科大学, 医学部附属病院, 准教授 (00242769)
• Co-Investigator(Kenkyū-buntansha): 山田 千亜希 浜松医科大学, 医学部附属病院, 臨床検査技師 (60770980)
• Research Collaborator: Oto Hitoshi ; Watanabe Hiroko ; Ishimaru Ken ; Kawabata Kinuyo ; Nomaguchi Yuriko ; Haraguchi Yasue ; Abe Misao ; Sobue Koki ; Takenouchi Hiroyuki ; Takadate Junko ; Kamimura Masami ; Katai Akiko ; Kasai Daisuke ; Minami Yumiko ; Sugimoto Tatsuya ; Michino Junko ; Nagai Kazuhiro ; Kumagai Mikako ; Hasegawa Yuichi ; Sato Hidehiro ; Takahashi Koki ; Fujii Satoshi ; Otomo Naoki ; Yonemura Yuji ; Yoshida Masaya ; Nagamine Keisuke ; Fujiwara Koki ; Maruyama Mitsuko ; Lee Etsuko ; Yamada Naotomo ; Hashimoto Makoto ; Buseki Yuji ; Hasegawa Mayumi ; Matsuura Hideaki ; Ishikawa Shinsuke ; Tanaka Kazuto ; Osawa Toshiya ; Shinohara Shigeru ; Tatsukawa Yoshiaki ; Sato Genshiro ; Nagamura Tokiko ; Matsunami Misako ; Okamoto Aya ; Oda Nozomi ; Kumano Yumiko ; Asahina Aya ; Nakagiri Itsuro ; Kochi Noriyo
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 赤血球不規則抗体 / 輸血副反応 / 抗原陽性輸血 / 輸血副作用 / アロ免疫 / 輸血学 / 免疫学

Outline of Final Research Achievements

We conducted the collaborative study to clarify the detail of antigen (Ag)-positive red blood cells (RBCs) transfusion to the patients conclusively having respective irregular antibodies (Abs). Totally, 826 cases were registered from 45 institutions. The main reasons for Ag-positive RBCs transfusion were ‘negative for indirect anti-globulin test (IAT)’ (35%) and ‘detection of warm auto-Ab’ (29%). Twenty-three cases (3%) observed the adverse reactions of some kind after Ag-positive RBCs transfusion. Anti-E, anti-Lea and anti-Jra Abs were determined in 6, 3 and 2 cases, respectively. Five (22%) of these 23 cases, who have anti-E (3 cases) or anti-Jra (2 cases), experienced clinically apparent hemolysis. Some cases had severe hemolytic adverse reactions after Ag-positive RBCs transfusion in several conceivable situations. We should monitor these transfused cases and start the treatment speedy when necessary.

Academic Significance and Societal Importance of the Research Achievements

不規則抗体陽性患者に当該抗原陽性輸血を行った症例を調査する本研究は世界的にも稀であり、日本発のエビデンスとして、不規則抗体保有患者への輸血の基礎データとなりうる。抗原陽性輸血の調査のシステムを構築することをめざす。本研究終了後も調査は恒常的に継続され、抗原陽性輸血のデータが蓄積されるシステムにする。それにより副反応の頻度や重症度等の数値は、より真の値へ近づき、世界的なガイドラインに引用される可能性が高い。

Research Products

• [Journal Article] Released washed platelet concentrates are effective and safe in patients with a history of transfusion reactions. (2019)
  • Author(s): Fujiwara SI, Fujishima N, Kanamori H, Ito M, Sugimoto T, Saito S, Sakaguchi T, Nagai K, Masuoka H, Nagai K, Morita A, Kino S, Tanaka A, Hasegawa Y, Yokohama A, Fujino K, Makino S, Matsumoto M, Takeshita A, Muroi K.
  • Journal Title: Transfus Apher Sci Volume: in press Pages: in press
  • DOI: 10.1016/j.transci.2018.09.001.
  • Peer Reviewed
• [Journal Article] Tamibarotene maintenance improved relapse-free survival of acute promyelocytic leukemia: a final result of prospective, randomized, JALSG-APL204 study. (2019)
  • Author(s): Takeshita A, Asou N, Atsuta Y, Sakura T, Ueda Y, Sawa M, Dobashi N, Taniguchi Y, Suzuki R, Nakagawa M, Tamaki S, Hagihara M, Fujimaki K, Furumaki H, Obata Y, Fujita H, Yanada M, Maeda Y, Usui N, Kobayashi Y, Kiyoi H, Ohtake S, Matsumura I, Naoe T, Miyazaki Y; and the Japanese Adult Leukemia Study Group.
  • Journal Title: Leukemia 2019 Volume: 33(2) Pages: 358-370
  • DOI: 10.1038/s41375-018-0233-7.
  • Peer Reviewed
• [Journal Article] Phase II study of FLAGM (fludarabin, high-dose cytarabine, granulocyte colony-stimulating factor, mitoxantrone) for relapsed or refractory acute myeloid leukemia. (2019)
  • Author(s): Hatsumi N, Miyawaki S, Yamauchi T, Takeshita A, Komatsu N, Usui N, Arai Y, Ishida F, Morii T, Kano Y, Ogura M, Machida S, Nishii K, Honda S, Ohnishi K, Naoe T.
  • Journal Title: Int J Hematol Volume: 109(4) Pages: 418-425
  • DOI: 10.1007/s12185-019-02606-0.
  • Peer Reviewed
• [Journal Article] Clinical significance of ASXL2 and ZBTB7A mutations and C-terminally truncated RUNX1-RUNX1T1 expression in AML patients with t(8;21) enrolled in the JALSG AML201 study. (2019)
  • Author(s): Kawashima N, Akashi A, Nagata Y, Kihara R, Ishikawa Y, Asou N, Ohtake S, Miyawaki S, Sakura T, Ozawa Y, Usui N, Kanamori H, Ito Y, Imai K, Suehiro Y, Kitamura K, Sakaida E, Takeshita A, Suzushima H, Naoe T, Matsumura I, Miyazaki Y, Ogawa S, Kiyoi H; Japan Adult Leukemia Study Group (JALSG).
  • Journal Title: Ann Hematol Volume: 98(1) Pages: 83-91
  • DOI: 10.1007/s00277-018-3492-5.
  • Peer Reviewed
• [Journal Article] Clinical impact of underweight status at diagnosis on elderly patients with acute myeloid leukemia: a retrospective study of JALSG GML200. (2018)
  • Author(s): Harada K, Doki N, Miyazaki Y, Wakita A, Ohtake S, Takada S, Komatsu H, Kubo K, Takeshita A, Adachi Y, Kiyoi H, Yamaguchi T, Yoshida M, Naoe T, Ohashi K.
  • Journal Title: Ann Hematol Volume: 97(8) Pages: 1481-1483
  • DOI: 10.1007/s00277-018-3281-1.
  • Peer Reviewed
• [Journal Article] Prognostic analysis according to the 2017 ELN risk stratification by genetics in adult acute myeloid leukemia patients treated in the Japan Adult Leukemia Study Group (JALSG) AML201 study (2018)
  • Author(s): Harada Y, Nagata Y, Kihara R, Ishikawa Y, Asou N, Ohtake S, Miyawaki S, Sakura T, Ozawa Y, Usui N, Kanamori H, Ito Y, Imai K, Suehiro Y, Kobayashi S, Kitamura K, Sakaida E, Onizuka M, Takeshita A, Ishida F, Suzushima H, Ishizawa K, Naoe T, Matsumura I, Miyazaki Y, Ogawa S, Kiyoi H.
  • Journal Title: Leuk Res Volume: 66 Pages: 20-27
  • DOI: 10.1016/j.ieukres. 2018. 01.008.
  • Peer Reviewed
• [Journal Article] 高校生献血の契機に関する意識調査（第2報） (2018)
  • Author(s): 保坂侑里, 山田千亜希, 藤原晴美, 古牧宏啓, 芝田大樹, 榛葉隆人 ,都築茉里子, 石塚恵子,渡邊弘子, 梶原道子, 浅井隆善, 室井一男, 竹下明裕.
  • Journal Title: 日本輸血細胞治療学会誌 Volume: 64(4) Pages: 608-613
  • Peer Reviewed
• [Journal Article] 末梢血幹細胞採取に携わる学会認定・アフェレーシスナースの活動に関する調査 (2018)
  • Author(s): 15.松本真弓, 西岡純子, 奥山美樹, 中川美子, 河野武弘, 藤原慎一郎, 池田和彦, 横濱章彦, 田中朝志, 長谷川雄一, 藤野惠三, 牧野茂義, 紀野修一, 竹下明裕, 池田和眞, 室井一男.
  • Journal Title: 日本輸血細胞治療学会誌 Volume: 64(4) Pages: 614-618
• [Journal Article] A national survey of premedication for transfusion reactions in Japan. (2017)
  • Author(s): Fujiwara SI, Takesita A, et al.
  • Journal Title: Transfus Apher Sci. Volume: 56 Pages: 708-12
  • DOI: 10.1016/j.transci.2017.07.024.
  • Peer Reviewed
• [Journal Article] Frequent somatic mutations in epigenetic regulators in newly diagnosed chronic myeloid leukemia. (2017)
  • Author(s): Togasaki E, Takeshita A
  • Journal Title: Blood Cancer J. Volume: 7 Pages: e559
  • DOI: 10.1038/bcj.2017.36.
  • Peer Reviewed
• [Journal Article] 高校生の献血意識に関する調査 (2016)
  • Author(s): 竹下明裕、古牧宏啓、浅井隆善、梶原道子、岩尾憲明、室井一男
  • Journal Title: 日本輸血細胞治療学会誌 Volume: 62(6) Pages: 711-17
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Recommendations for the electronic pre-transfusion check at the bedside. (2016)
  • Author(s): Ohsaka A, Kato H, Kino S, Kawabata K, Kitazawa J, Sugimoto T, Takeshita A, Baba K, Hamaguchi M, Fujii Y, Horiuchi K, Yonemura Y, Hamaguchi I, Handa M
  • Journal Title: Blood Transfusion Volume: 14(5) Pages: 419-24
  • DOI: 10.2450/2016.0184-15
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Involvement of transfusion unit staff in the informed consent process. (2016)
  • Author(s): Furumaki H, Fujihara H, Yamada C, Watanabe H, Shibata H, Kaneko M, Nagai S, Ishizuka K, Tsuzuki M, Adachi M, Takeshita A.
  • Journal Title: Transfus Apheresis and Sciences Volume: 54(1) Pages: 150-7
  • DOI: 10.1016/j.transci.2015.12.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] クリオプレシピテート院内作製プロトコール (2016)
  • Author(s): 大石 晃嗣, 松本 剛史, 田中 由美, 牧野 茂義, 玉木 茂久, 森 恵子, 藤盛 好啓, 池本 純子, 岩尾 憲明, 加藤 栄史, 紀野 修一, 竹下 明裕, 山田 千亜希, 藤井 聡, 渡辺 直樹, 大塚 浩平, 山本 晃士, 星野 鉱二, 宮崎 研一, 前田 平生, 宮田 茂樹,
  • Journal Title: 日本輸血細胞治療学会誌 Volume: 62(6) Pages: 664-72
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 赤血球型検査(赤血球系検査)ガイドライン(改訂2版) (2016)
  • Author(s): 奥田 誠, 石丸 健, 内川 誠, 梶原 道子, 北澤 淳一, 国分寺 晃, 小林 信昌, 小山 典久, 高橋 智哉, 竹下 明裕, 安田 広康
  • Journal Title: 日本輸血細胞治療学会誌 Volume: 62(6) Pages: Page651-63
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Multi-center collaborative study on antigen-positive red blood cell (RBC) transfusion for the patients who have irregular RBC antibodies. (2018)
  • Author(s): Yamada C, Takeshita A, Tadokoro K, Ohto H, Watanabe H, Kawabata K, Nomaguchi Y, Sobue K, Haraguchi Y, Abe M.
  • Organizer: Annual Meeting of the American Association of Blood Bank (AABB)
  • Int'l Joint Research
• [Presentation] CD56 Is an Unfavorable Prognostic Factor for Acute Promyelocytic Leukemia: Results By Multivariate Analyses in the JALSG-APL204 Study (2018)
  • Author(s): Takeshita A, Asou N, Yanada M, Sakura T, Ueda Y, Sawa M, Dobashi N, Onizuka M, Taniguchi Y, Nakagawa M, Tamaki S, Hagihara M, Fujimaki K, Furumaki H, Fujita H, Usui N, Kobayashi Y, Kiyoi H, Ohtake S, Atsuta Y, Matsumura I, Naoe T, Miyazaki Y.
  • Organizer: The 60th Annual Meeting and Exposition of the American Society of Hematology
  • Int'l Joint Research
• [Presentation] JALSG prospective study (2018)
  • Author(s): Takeshita A.
  • Organizer: The 60th Spring International Congress Meeting of the Korean Society of Hematology
  • Int'l Joint Research / Invited
• [Presentation] Daratumumab投与における輸血検査への影響とその対処法. (2018)
  • Author(s): 山田千亜希, 竹下明裕, 藤原晴美, 古牧宏啓, 芝田大樹, 奥田 誠, 川畑絹代, 万木紀美子, 前川 平, 岡崎 仁, 大戸 斉.
  • Organizer: 第66回日本輸血・細胞治療学会総会
• [Presentation] フローサイトメトリーを用いたDaratumumabによるCD38抗原の感作と処理に関する検討 (2018)
  • Author(s): 古牧宏啓, 竹下明裕, 藤原晴美, 山田千亜希, 芝田大樹, 奥田 誠, 川畑絹代, 万木紀美子, 前川 平, 岡崎 仁, 大戸 斉.
  • Organizer: 第66回日本輸血・細胞治療学会総会
• [Presentation] JALSG prospective study. (2018)
  • Author(s): Takeshita A.
  • Organizer: The 60th Spring International Congress Meeting of the Korean Society of Hematology. Soul, Korea
  • Int'l Joint Research / Invited
• [Presentation] Previous and recent JALSG studies for acute promyelocytic leukemia. (2017)
  • Author(s): Takeshita A.
  • Organizer: Japan Adult Leukemia Study Group 30th anniversary International Symposium. Tokyo, Japan
  • Invited
• [Presentation] Recent results from the prospective studies on APL in the Japan Adult Leukemia Study Group (JALSG). (2017)
  • Author(s): Takeshita A.
  • Organizer: The 7th International Symposium on Acute Promyelocytic Leukemia. Roma, Italy
  • Int'l Joint Research / Invited
• [Presentation] The collaborative study of irregular erythrocyte antibodies in Japan. International Symposium. (2017)
  • Author(s): Takeshita A.
  • Organizer: The 65th Annual Meeting of Japanese Society of Transfusion and Cell Therapy, Makuhari, Japan,
  • Invited
• [Presentation] Tamibarotene as maintenance therapy for acute promyelocytic leukemia improved long term relapse-free survival: 7-year results from a randomized controlled trial, JALSG-APL204. (2017)
  • Author(s): Takeshita A, et al.
  • Organizer: The 59th Annual Meeting and Exposition of the American Society of Hematology. Atlanta, USA.
  • Int'l Joint Research
• [Presentation] 分子標的治療が輸血検査に与える影響」‐輸血部門が知っておきたい薬剤とその対応 (2017)
  • Author(s): 竹下明裕.
  • Organizer: 第65回日本輸血細胞治療学会総会
  • Invited
• [Presentation] 高校生の体格が献血行動に及ぼす影響 (2016)
  • Author(s): 保坂 侑里, 藤原 晴美, 芝田 大樹, 榛葉 隆人, 都築 茉里子, 石塚 恵子, 古牧 宏啓, 山田 千亜希, 渡邊 弘子, 金子 誠, 室井 一男, 竹下 明裕
  • Organizer: 第64回 日本輸血細胞治療学会総会
  • Place of Presentation: 京都国際会議場(京都)
  • Year and Date: 2016-04-28 – 2016-04-30
• [Presentation] 高校生を対象とした献血に関する意識調査 献血の契機となったこと (2016)
  • Author(s): 榛葉 隆人, 藤原 晴美, 保坂 侑里, 芝田 大樹, 都築 茉里子, 石塚 恵子, 古牧 宏啓, 山田 千亜希, 渡邊 弘子, 金子 誠, 室井 一男, 竹下 明裕
  • Organizer: 第64回 日本輸血細胞治療学会総会
  • Place of Presentation: 京都国際会議場（京都）
  • Year and Date: 2016-04-28 – 2016-04-30
• [Presentation] 不規則抗体陽性患者に対する赤血球製剤輸血に関する共同研究の進捗状況 (2016)
  • Author(s): 山田 千亜希, 田所 憲治, 渡邊 弘子, 原口 安江, 阿部 操, 祖父江 晃基, 佐々木 さき子, 杉本 達哉, 野間口 由利子, 道野 淳子, 石丸 健, 宮城 徹, 竹下 明裕
  • Organizer: 第64回 日本輸血細胞治療学会総会
  • Place of Presentation: 京都国際会議場（京都）
  • Year and Date: 2016-04-28 – 2016-04-30
• [Presentation] 赤血球不規則抗体に関する国際共同研究 (2016)
  • Author(s): 竹下明裕
  • Organizer: 第64回 日本輸血細胞治療学会総会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2016-04-28 – 2016-04-30
  • Invited
• [Presentation] 術中迅速検査の導入による適正輸血の推進に果たす輸血部門の役割 (2016)
  • Author(s): 山田 千亜希, 藤原 晴美, 渡邊 弘子, 金子 誠, 芝田 大樹, 古牧 宏啓, 石塚 恵子, 都築 茉里子, 榛葉 隆人, 保坂 侑里, 竹下 明裕
  • Organizer: 第64回 日本輸血細胞治療学会総会
  • Place of Presentation: 京都国際会議場（京都）
  • Year and Date: 2016-04-28 – 2016-04-30
• [Presentation] アルブミン製剤以外の血漿分画製剤の一元管理による適正使用の推進 (2016)
  • Author(s): 古牧 宏啓, 山田 千亜希, 芝田 大樹, 石塚 恵子, 榛葉 隆人, 保坂 侑里, 都築 茉里子, 藤原 晴美, 渡邊 弘子, 金子 誠, 竹下 明裕
  • Organizer: 第64回 日本輸血細胞治療学会総会
  • Place of Presentation: 京都国際会議場（京都）
  • Year and Date: 2016-04-28 – 2016-04-30
• [Book] 急性骨髄性白血病 10.血液疾患 今日の治療指針 (2017)
  • Author(s): 竹下明裕.
  • Total Pages: 1999
  • Publisher: 医学書院
  • ISBN: 978-4-26-02809-7
• [Book] がん看護 血液がん～最新治療と支持療法～】 (第III章)新規薬剤による治療戦略とケアの実際 白血病 急性骨髄性白血病 (2017)
  • Author(s): 竹下明裕
  • Total Pages: 294 (180-187)
  • Publisher: 南江堂
• [Book] 105 CD33発現とGOの効き方 (2016)
  • Author(s): 竹下明裕
  • Total Pages: 649-654 (627-631)
  • Publisher: 科学評論社
• [Book] 白血病学(下) 最新の基礎、臨床研究 白血病治療の副作用・合併症対策と支持療法 化学療法の副作用・合併症対策 非血液毒性 (2016)
  • Author(s): 竹下明裕
  • Total Pages: 582 (315-322)
  • Publisher: 日本臨床社
• [Book] 急性骨髄性白血病診療の最前線 Anthracyclineの至適投与量に関する大規模試験 (2016)
  • Author(s): 竹下明裕
  • Total Pages: 167-278 (189-192)
  • Publisher: 科学評論社