Establishment of early and simple diagnostic method for complications and recurrence after hematopoietic stem cell transplantation

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09017
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Osaka City University
• Principal Investigator: HINO MASAYUKI 大阪市立大学, 大学院医学研究科, 教授 (50244637)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 造血幹細胞移植 / 免疫回復 / サイトカイン放出症候群 / 類洞閉塞症候群 / インターロイキン6 / 経直腸門脈シンチグラフィー / WT1 / PT/Cy

Outline of Final Research Achievements

The pretransplant WT1 mRNA level was a powerful prognostic factor in allo-HCT for non-CR AML patients. High peak serum IL-6 level after HLA-haploidentical allogeneic hematopoietic cell transplantation with post-transplantation cyclophosphamide (PT/Cy-haplo) was identified a significant risk factor for very severe cytokine release syndrome (CRS) and poor 3-year overall survival. Counts of CD4+ T-cell subsets, CD8+ T-cell subsets, and NK cells were lower in PT/Cy-haplo than those in HLA-matched related HCT. The immune recovery pace in PT/Cy-haplo subsequently caught up with that of the other grafts. The regulatory T cells (Tregs) to conventional CD4+ T-cell (Tcon) ratio was significantly higher in PT/Cy-haplo. A higher Tregs-to-Tcon ratio was significantly associated with a lower incidence of chronic GVHD. A diagnostic approach using per-rectal portal scintigraphy for sinusoidal obstruction syndrome was useful.

Free Research Field

血液内科

Academic Significance and Societal Importance of the Research Achievements

WT1が非寛解急性骨髄性白血病に対する同種造血幹細胞移植の有用な予後因子であることを示し、移植適応を考える上で有用となる。移植後大量シクロフォスファミドを用いたHLA半合致移植（PT/Cyハプロ移植）後に発症し、生命を脅かす可能性があるサイトカイン放出症候群の代理マーカーとしてIL-6を見出し、診断および治療法の開発に有用となる。PT/Cyハプロ移植後の免疫回復を明らかにし、CD4 + T細胞/制御性T細胞比が低いことが慢性GVHDが少ない機序である可能性を示した。非侵襲的門脈圧測定法である経直腸門脈シンチグラフィーが診断困難な移植後類洞閉塞症候群の診断法として有用であることを示した。