Establishing biomarkers for assessment of intestinal mucosal injury in hematopietic stem cell transplantation

• Project/Area Number: 25461454
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: International University of Health and Welfare
• Principal Investigator: Fukushima Noriyasu 国際医療福祉大学, 福岡保健医療学部, 教授 (20346894)
• Co-Investigator(Kenkyū-buntansha): 久保田 寧 佐賀大学, 医学部, 病院講師 (60570413)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
• Keywords: 血液内科学 / 造血幹細胞移植 / 化学療法 / 合併症 / バイオマーカー / 腸管粘膜損傷 / diamine oxidase / シトルリン / 栄養指標 / 消化管機能

Outline of Final Research Achievements

Gastrointestinal tract mucositis is a common side effect when performing stem cell transplantation (SCT). Citrulline and diamine oxidase (DAO) levels are reported as specific markers of intestinal mucosal injury during cancer chemotherapy. We investigated whether the serial monitoring of these markers is useful to assess the severity of gastrointestinal tract complications during the early phase of reduced-intensity regimens, following cord blood stem cell transplantation (CBT).
Serial monitoring of plasma citrulline, serum DAO levels and some laboratory parameters were performed in paients received HSCT.Both citrulline and DAO levels significantly decreased after the start of conditioning. Of note, the recovery of citrulline and DAO levels was delayed in the CBT group. The serial monitoring of citrulline and DAO levels might be promising biomarkers for assessing intestinal mucosal injury during CBT in clinical decision making.

Research Products

• [Journal Article] Acute myeloid leukemia with t(3;8)(q26;q24) complicated by diabetes insipidus. (2016)
  • Author(s): Kubota Y, Ichinohe T, Yoshimura M, Itamura H, Hisatomi T, Fukushima N, Sueoka E, Kimura S.
  • Journal Title: Annals of Hematology Volume: 95 Issue: 4 Pages: 653-655
  • DOI: 10.1007/s00277-016-2595-0
  • Peer Reviewed
• [Journal Article] Famotidine-induced reactive plasmacytosis and generalized lymphadenopathy: a case report and review of the literature (2016)
  • Author(s): Hiroaki Kitamura, Yasushi Kubota, Noriyasu Fukushima, Tatsuo Ichinohe, Daisuke Hayasaka, Kazuharu Kamachi, Mari Yoshihara, Hidekazu Itamura, Takashi Hisatomi, Kazuo Wakayama, Eisaburo Sueoka, Shinya Kimura
  • Journal Title: Int J Clin Exp Pathol Volume: 9 Pages: 7680-7685
  • Peer Reviewed / Open Access
• [Journal Article] High incidence of activating STAT5B mutations in CD4-positive T-cell large granular lymphocyte leukemia. (2016)
  • Author(s): Andersson E, Tanahashi T, Sekiguchi N, Gasparini VR, Bortoluzzi S, Kawakami T, Matsuda K, Mitsui T, Eldfors S, Bortoluzzi S, Coppe A, Binatti A, Lagstrom S,Ellonen P, Fukushima N, Nishina S, Senoo N, Sakai H, Nakazawa H, Kwong YL, Loughran TP, Maciejewski JP, Mustjoki S, Ishida F.
  • Journal Title: Blood Volume: 128 Issue: 20 Pages: 2465-2468
  • DOI: 10.1182/blood-2016-06-724856
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Monitoring of Hepatitis B Virus (HBV) DNA and Risk of HBV Reactivation in B-cell Lymphoma: A prospective observational study. (2015)
  • Author(s): Kusumoto S, Tomita A, et al. （35名中27番目）
  • Journal Title: Clin Infect Dis. Volume: 61 Issue: 5 Pages: 719-29
  • DOI: 10.1093/cid/civ344
  • Peer Reviewed
• [Journal Article] "Coexistence of ALK- anaplastic large cell lymphoma and CD4+ T-cell large granular lymphocytic leukemia " (2015)
  • Author(s): Kazuharu Kamachi1, Noriyasu Fukushima, Toshihiko Ando, Ken-ichi Sato, Koichi Ohshima, Masako Yokoo, Takero Shindo, Yasushi Kubota, Kensuke Kojima, Shinya Kimura
  • Journal Title: Ann Hematol Volume: 94 Issue: 3 Pages: 539-540
  • DOI: 10.1007/s00277-014-2176-z
  • Peer Reviewed
• [Journal Article] Therapeutic management in cardiac lymphoma. (2014)
  • Author(s): Yoshihara M, Itamura H, Fukushima N, Itoh M, Furukawa K, Nagatomo D, Kamachi K, Kitamura H, Shindo T, Kubota Y, Sueoka E, Morita S, Ichinohe T, Kimura S.
  • Journal Title: Leukemia and Lymphoma Volume: 55 Issue: 5 Pages: 1215-1217
  • DOI: 10.3109/10428194.2013.828355
  • Peer Reviewed
• [Journal Article] Japan Clinical Oncology Group (JCOG) prognostic index and characterization of long-term survivors of aggressive adult T-cell leukaemia-lymphoma (JCOG0902A). (2014)
  • Author(s): Fukushima T, Nomura S, Shimoyama M, Shibata T, Imaizumi Y, Moriuchi Y, Tomoyose T, Uozumi K, Kobayashi Y, Fukushima N, Utsunomiya A, Tara M, Nosaka K, Hidaka M, Uike N, Yoshida S, Tamura K, Ishitsuka K, Kurosawa M, Nakata M, Fukuda H, Hotta T, Tobinai K, Tsukasaki K.
  • Journal Title: Br J Haematol Volume: 166 Issue: 5 Pages: 739-748
  • DOI: 10.1111/bjh.12962
  • Peer Reviewed
• [Journal Article] ABL tyrosine kinase inhibitor–induced pulmonary alveolar proteinosis in chronic myeloid leukemia (2014)
  • Author(s): Mariko Yoshimura, Kensuke Kojima, Rika Tomimasu, Noriyasu Fukushima, Shinichiro Hayashi, Eisaburo Sueoka, Shinya Kimura
  • Journal Title: Int J Hematol Volume: 100 Issue: 6 Pages: 611-614
  • DOI: 10.1007/s12185-014-1666-z
  • Peer Reviewed
• [Journal Article] A Novel Frameshift Mutation in Exon 4 Causing a Deficiency of High-molecular-weight Kininogen in a Patient with Splenic Infarction (2014)
  • Author(s): Fukushima N, Itamura H, Wada H, Ikejiri M, Igarashi Y, Masaki H, Sano M, Komiyama Y, Ichinohe T, Kimura S.
  • Journal Title: Internal Medicine Volume: 53 Issue: 3 Pages: 253-257
  • DOI: 10.2169/internalmedicine.53.0737
  • NAID: 130003392631
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed
• [Journal Article] 輸血後鉄過剰症の現状と問題点 (2013)
  • Author(s): 末岡榮三朗、山田尚友、山田麻里江、久保田寧、浦田千紗子、吉村麻里子、 板村英和、久富崇、 福島伯泰、出勝、横尾眞子、 吉原麻里、蒲池和晴、 北村浩晃、 進藤岳郎、一戸辰夫、東谷孝徳、木村晋也
  • Journal Title: 日本輸血細胞治療学会雑誌 Volume: 59 Pages: 73-78
  • NAID: 10031165492
  • Peer Reviewed
• [Presentation] 造血幹細胞移植時の消化管粘膜障害評価に関するバイオマーカーの検討 (2016)
  • Author(s): 富安聡、福島伯泰、末岡榮三朗、木村晋也
  • Organizer: 第63回日本臨床検査医学会学術集会
  • Place of Presentation: 神戸国際会議場他
  • Year and Date: 2016-09-01
• [Presentation] 血清diamine oxidaseの経時的測定を使用した造血幹細胞移植時消化管合併症評価の有用性の検討 (2015)
  • Author(s): 福島伯泰、末岡榮三朗、木村晋也
  • Organizer: 第62回日本臨床検査医学会学術集会
  • Place of Presentation: 岐阜市
  • Year and Date: 2015-11-19
• [Presentation] Prognostic biomarkers in patients with locakized NK/T-cell lymphoma treated with RT-DeVIC (2014)
  • Author(s): Takata, K, Yamaguchi M,Yoshino T,Ishizuka T, Oguchi M, Kobayashi Y, Isobe Y, Ishizawa K, Kubuto N, Itoh K, Usui N, Miyazaki K, Utsumi T, Masaki Y, Nosaka K, Fukushima N, Ohmachi K, Shimada K Morimoto H, Tsukamoto N, Inoue Y, Yakushijin Y, Wasada I, Nakamura S, Matsuo Y, Oshimi K, Kinoshita T, Tsukasaki K, Tobinai K
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] 悪性リンパ腫における臨床病理学的手法を用いた予後因子マーカーの探索～Ｔ細胞性大顆粒リンパ球性白血病と未分化大細胞リンパ腫の合併例におけるSTAT3変異の解析~ (2014)
  • Author(s): 福島伯泰、佐藤謙一、蒲池和晴、木村晋也
  • Organizer: 第4回国際医療福祉大学学会学術集会
  • Place of Presentation: 国際医療福祉大学
  • Year and Date: 2014-08-30 – 2014-08-31
• [Presentation] 高分子キニノゲン欠乏症の血漿プレカリクレイン活性測定における試薬選択の重要性 (2014)
  • Author(s): 五十嵐裕子、小宮山豊、樫原雅美、畑上真緒、平城均、福島伯泰、木村晋也、正木浩哉、高橋伯夫
  • Organizer: 第15回日本検査血液学会学術集会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2014-07-20 – 2014-07-21
• [Presentation] 電子カルテと輸血管理システムの連携による輸血後鉄過剰症モニタリングプログラムの運用 (2013)
  • Author(s): 末岡榮三朗、山田尚友、山田麻里江、久保田寧、福島伯泰、東谷孝徳、木村晋也
  • Organizer: 第61回日本輸血・細胞治療学会総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] HTLV-1専門外来におけるカウンセリング体制の整備と運用状況 (2013)
  • Author(s): 柘植薫、久保田寧、福島伯泰、一戸辰夫、木村晋也、末岡榮三朗
  • Organizer: 第61回日本輸血・細胞治療学会総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 成人血球貪食性リンパ組織球症の診断契機と治療 (2013)
  • Author(s): 吉村麻里子、板村英和、横尾眞子，出勝，久富崇，久保田寧，福島伯泰，末岡榮三朗，木村晋也
  • Organizer: 第53回日本リンパ網内系学会総会
  • Place of Presentation: 京都国際会議場
• [Presentation] Therapeutic management in cardiac lymphoma. (2013)
  • Author(s): Yoshihara M, Itamura H, Fukushima N, Kamach K, Kitamura H, Shindo T, Kubota Y, Sueoka E, Ichinohe T, Kimura S
  • Organizer: 第11回日本臨床腫瘍学会
  • Place of Presentation: 仙台国際会議場他
• [Presentation] A case of anaplastic large cell lymphoma, ALK- with T-LGL leukemia expressing aberrant phenotype (2013)
  • Author(s): Kazuharu Kamachi, Noriyasu Fukushima, Hiroaki Kitamura, Mari Yoshihara, Hidekazu Itamura, Mariko Yoshimura, Masako Yokoo, Masaru Ide, Takero Shindo, Yasushi Kubota, Toshihiko Ando, Tatsuo Ichinohe, Eisabuzo Sueoka, Koichi Ohshima, Shinya Kimura
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: ロイトン札幌他
• [Presentation] 造血器腫瘍患者の中心静脈カテーテル関連血流感染症の発生に環境による違いはあるのか？ (2013)
  • Author(s): 北村浩晃、久保田寧、金子ゆかり、蒲池和晴、吉原麻里、板村英和、進藤岳郎、福島伯泰、安藤寿彦、末岡榮三朗、青木洋介、木村晋也
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: ロイトン札幌他
• [Presentation] Deferasirox in iron-overloaded patients with hematologic diseases at Saga University Hospital (2013)
  • Author(s): Abe O, Yoshihara M, Kubota Y, Sueoka E, Kamachi K, Kitamura H, Itamura H, Nishi M, Shindo T, Fukushima N, Hamasaki Y, Kimura S
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: ロイトン札幌他
• [Presentation] Efficacy of Melphalan/Predon- isolone/Bortezomib(MPB) therapy for patients with multiple myeloma (2013)
  • Author(s): Takashi Hisatomi Seiji Kondo, Noriyasu Fukushima, Eijo Matsuishi, Yasushi Kubota, Takero Shindo, Hisashi Gondo, Shinya Kimura
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 京都国際会議場