Identification of genotypes in immune-related genes predicting outcomes in patients following allogeneic hematopoietic cell transplantation

• Project/Area Number: 18K17388
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 58030:Hygiene and public health-related: excluding laboratory approach
• Research Institution: Osaka City University
• Principal Investigator: Koh Hideo 大阪市立大学, 大学院医学研究科, 講師 (90419698)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 同種造血幹細胞移植 / 分子疫学 / 血液悪性腫瘍 / 腫瘍再発抑制 / NK細胞 / 急性GVHD / 予後予測 / 治療標的分子

Outline of Final Research Achievements

We retrospectively examined consecutive patients who received HLA-haploidentical allogeneic hematopoietic cell transplantation using post-transplantation cyclophosphamide (PT/Cy-haplo) at our institution between June 2009 and December 2018. Sixteen KIR genes were genotyped. A total of 91 patients were eligible. In complete remission population at PT/Cy-haplo, the patients who underwent PT/Cy-haplo from a KIR2DS1-positive donor had significantly lower rates of cumulative incidence of relapse (CIR) and higher rates of overall survival (OS) than those from a KIR2DS1-negative donor (2-year CIR, 9.2% vs 42%; P = 0.037; 2-year OS, 83% vs 34%; P = 0.01). In non-complete remission population at PT/Cy-haplo, however, PT/Cy-haplo from a KIR2DS1-positive donor did not significantly improve CIR or OS. These data suggest that to test the inclusion of donor KIR genotyping and tumor burden evaluations may contribute to establishing optimal donor selection criteria at PT/Cy-haplo.

Academic Significance and Societal Importance of the Research Achievements

現在、PT/Cyハプロ移植は、その安全性、低コスト、血縁ドナーのため迅速に移植が行える利点により、世界で急速に広まっている。今後少子化社会が予想される本邦においても期待されるが、両親や同胞の複数のドナー候補のうち最適なドナーの選択法については未確立である。本研究では、血液悪性腫瘍の寛解患者において KIR遺伝子型KIR2DS1陽性ドナーから移植した場合に、陰性ドナーからの移植と比較して、2年再発率、2年生存率とも著明に改善することを示した。再発を抑制し、生存率を改善するドナー選択法を提供する本結果は、本邦でのPT/Cyハプロ移植における最適なドナー選択アルゴリズムの確立に寄与する可能性がある。

Research Products

• [Journal Article] Donor KIR2DS1-Mediated Decreased Relapse and Improved Survival Depending on Remission Status at HLA-Haploidentical Transplantation with Post-Transplantation Cyclophosphamide. (2019)
  • Author(s): Ido K, Koh H, Hirose A, Okamura H, Koh S, Nanno S, Nishimoto M, Nakamae M, Nakashima Y, Nakane T, Hino M, Nakamae H.
  • Journal Title: Biology Blood Marrow Transplantation も含めた検索結果を表示しています Biol Blood Marrow Transplant のみで検索 検索結果 ウェブの結果（サイトリンク付き） Biology of Blood and Marrow Transplantation Volume: － Issue: 4 Pages: 723-733
  • DOI: 10.1016/j.bbmt.2019.12.765
  • Peer Reviewed
• [Presentation] PTCyハプロ移植におけるドナーKIR2DS1の再発抑制効果は移植時病期に依存する (2020)
  • Author(s): 井戸健太郎、康 秀男、岡村浩史、康 史朗、南野 智、西本光孝、廣瀬朝生、中前美佳、中嶋康博、中根孝彦、日野雅之、中前博久
  • Organizer: 第42回日本造血細胞移植学会総会
• [Presentation] Impact of Donor KIR and HLA Genotypes on Clinical Outcomes According to Pre-Transplant Remission Status after HLA-Haploidentical Transplantation with Post-Transplantation Cyclophosphamide (2019)
  • Author(s): Kentaro Ido, Hideo Koh, Hiroshi Okamura, Shiro Koh, Satoru Nanno, Mitsutaka Nishimoto, Asao Hirose, Mika Nakamae, Yasuhiro Nakashima, Takahiko Nakane, Masayuki Hino, Hirohisa Nakamae.
  • Organizer: 61th American Society of Hematology, Orlando
  • Int'l Joint Research