Immune-escape mechanism of relapsed leukemic cells after multiple transplantation
| Project/Area Number |
18K08376
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
海田 勝仁 兵庫医科大学, 医学部, 助教 (00441254)
小川 誠司 京都大学, 医学研究科, 教授 (60292900)
南谷 泰仁 京都大学, 医学研究科, 特定准教授 (60451811)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | HLA不適合造血幹細胞移植 / 白血病 / 再発 / GVHD / HLA / 不適合移植 / HLA不適合移植 / HLA-LOH |
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| Outline of Final Research Achievements |
We planed in vitro assays and a clinical trial concerning the theses that both HLA haplotypes could be lost after HLA-mismatched transplantations, and if not, 2-HLA-haplotype mismatched transplantation may be beneficial. Since the Corona pandemic led to difficulty in smoothly performing the in vitro assays, we focused on the clinical trial of 2-HLA-haplotype mismatched transplantation.
2-HLA-haplotype mismatched transplantation targets both HLA haplotypes at once, and the analyses of the relapsed leukemic cells after this type of transplantation may be a clue to the former question. In the clinical trial of 2-HLA-haplotype mismatched transplantation, all 30 cases except a case of early death achieved engraftment. The incidence of severe acute GVHD was 16.7%, and the rates of one-year overall survival, relapse, and non-relapse mortality were 30.1%, 38.9%, and 44.3%, respectively.
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| Academic Significance and Societal Importance of the Research Achievements |
HLA半合致移植は急速に普及してきたが、標的となるHLAを消失して白血病が再発することが知られている。では残ったHLAを標的とする再移植をすれば、両方のHLAを落とすのだろうか。HLA消失機序の解析によれば、一方は落とせても両方は無理なことが予想される。もしそうなら、両方のHLAを標的とする移植を行えば、HLA消失による再発は克服できる。我々は両方のHLAが異なる移植（両HLAハプロタイプ不適合移植）の臨床試験を行い、これが実際に可能であることを示した。これによって、もはやHLAの制約から移植を断念する必要はなくなり、再移植でしか助からない症例に、更なる移植の機会を提供することが可能となった。
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Report
(4 results)
Research Products
(3 results)
