International study for effect of ethnicity on the outcome of hematopoietic stem cell transplantation from unrelated donor.

• Project/Area Number: 16K09884
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Aichi Medical University (2017-2019); Aichi Cancer Center Research Institute (2016)
• Principal Investigator: Morishima Yasuo 愛知医科大学, その他部局等, 客員教授 (20220056)
• Project Period (FY): 2016-10-21 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 非血縁者間造血幹細胞移植 / 人種 / HLA / ｈLA / 造血幹細胞移植 / 造血細胞移植 / 国際組織適合性ワークショップ / 造血幹細胞移植学

Outline of Final Research Achievements

Hematopoietic stem cell transplantation from unrelated donor has been performed as a curative therapy for hematological malignancies internationally. This study focused on the impact of patient/donor ethnicity and its HLA on transplant outcomes. International Histocompatibility Workshop database has been constructed collecting HLA-A, B, C, DRB1,DQB1 and DPB1 alleles and clinical transplant related data. We could collect and analyzed 33,348 pairs with the ethnicity of Caucasian, Asian, Hispanic or Black. Survival rate after transplantation in Caucasian was lower than Asian, and higher than Hispanic and Black significantly. Incidence of graft-versus-host disease and graft-versus-leukemia depended on each ethnicity, HLA mismatch number and each HLA locus matching.

Academic Significance and Societal Importance of the Research Achievements

非血縁者間造血幹細胞移植はそれぞれの国のレジストリー（骨髄バンクなど）を介して実施されており、異なった人種での移植成績が報告されている。本国際研究ではHLA-A～DPB1の精緻なアレル情報と臨床データを共有する多数例の共通データを解析することにより、人種別（白人、アジア人、ヒスパニック系、黒人）の移植成績を明らかにすることができた。とくにHLA不適合非血縁移植の人種間の比較成績と関連する人種特異的なHLAとの関連につき世界で初めて明らかにすることができた。今後の人種内、人種間の非血縁移植の成績向上に資する基本的な知見となろう。

Research Products

• [Int'l Joint Research] Fred Hutchinson Cancer Research Center(米国)
• [Int'l Joint Research] Fred Hutchinson Cancer Research Center(米国)
• [Journal Article] Impact of homozygous conserved extended HLA haplotype on single cord blood transplantation: Lessons for induced pluripotent stem cell banking and transplantation in allogeneic settings. (2020)
  • Author(s): Morishima Y, Morishima S, Murata M, Arima N, Uchida N, Sugio Y, Takahashi S, Matsuhashi Y, Onizuka M, Eto T, Nagafuji K, Onishi Y, Inoue M, Atsuta Y, Fukuda T, Ichinohe T, Kato S, Kanda J.
  • Journal Title: Biology of Blood and Marrow Transplantation Volume: 26 Issue: 1 Pages: 132-138
  • DOI: 10.1016/j.bbmt.2019.09.009
  • Peer Reviewed
• [Journal Article] Risk of HLA Homozygous Cord Blood Transplantation (2018)
  • Author(s): Yasuo Morishima, et al.
  • Journal Title: Stem Cells Translational Medicine Volume: 7 Pages: 173-179
  • Peer Reviewed / Open Access
• [Journal Article] Risk of HLA Homozygous Cord Blood Transplantation: Implications for Induced Pluripotent Stem Cell Banking and Transplantation. (2018)
  • Author(s): Morishima Y, Azuma F, Kashiwase K, Matsumoto K, Orihara T, Yabe H, Kato S, Kato K, Kai S, Mori T, Nakajima K, Morishima S, Satake M, Takanashi M, Yabe T
  • Journal Title: Stem Cells Transl Med. Volume: 7(2) Issue: 2 Pages: 173-179
  • DOI: 10.1002/sctm.17-0169
  • Peer Reviewed / Open Access
• [Journal Article] Evolutionary basis of HLA-DPB1 alleles affects acute GVHD in unrelated donor stem cell transplantation. (2018)
  • Author(s): Morishima S, Shiina T, Suzuki S, Ogawa S, Sato-Otsubo A, Kashiwase K, Azuma F, Yabe T, Satake M, Kato S, Kodera Y, Sasazuki T, Morishima Y
  • Journal Title: Blood Volume: 131(7) Issue: 7 Pages: 808-817
  • DOI: 10.1182/blood-2017-08-801449
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] HLA-DPB1 mismatch induces a graft-versus-leukemia (GVL) effect without severe acute GVHD after single-unit umbilical cord blood transplantation (2018)
  • Author(s): Yabe T, Azuma F, Kashiwase K, Matsumoto K, Orihara T, Yabe H, Kato S, Kato K, Kai S, Mori T, Morishima S, Satake M, Takanashi M, Nakajima K, Morishima Y
  • Journal Title: Leukemia Volume: 168-175 Issue: 1 Pages: 168-175
  • DOI: 10.1038/leu.2017.202
  • Peer Reviewed
• [Presentation] Impact of homozygous conserved extended HLA haplotype on cord blood transplantation. (2018)
  • Author(s): Morishima Y, et al.
  • Organizer: American Society of Hematology
  • Int'l Joint Research
• [Presentation] IHWG Study of the Roe of Ethnicity in HLA-mismatched HCT. (2017)
  • Author(s): Yasuo Morishima
  • Organizer: The 17th International & Immunogenetics Workshop
  • Int'l Joint Research