Analysis of biomarkers and mechanisms of late effects after hematopoietic cell transplantation

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K08345
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: National Cancer Center Japan
• Principal Investigator: INAMOTO YOSHIHIRO 国立研究開発法人国立がん研究センター, 中央病院, 医長 (70730349)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 造血細胞移植 / 晩期障害 / バイオマーカー / 移植片対宿主病 / 二次がん

Outline of Final Research Achievements

We identified Dickkopf-related protein 3 (DKK3), a Wnt signaling modulator, as a novel plasma biomarker for chronic graft-versus-host disease (GVHD) including fibrotic phenotype. We demonstrated the utility of plasma MMP9 for diagnosis and response prediction of bronchiolitis obliterans syndrome to FAM therapy. We characterized and compared the incidence, manifestations and treatment outcomes of chronic GVHD and late acute GVHD between Japanese and Caucasian patients. I participated in a member of 2020 NIH Consensus Development Project on Criteria for Clinical Trials in Chronic GVHD and published several meeting reports. By using national transplant registry database and national cancer registration database, we reported outcomes of patients who developed subsequent solid cancer after hematopoietic cell transplantation. By using national transplant registry database, we characterized myeloid neoplasms following allogeneic hematopoietic cell transplantation.

Free Research Field

造血細胞移植

Academic Significance and Societal Importance of the Research Achievements

本研究は海外との共同研究も行いながら、同種造血細胞移植後の大きな課題である慢性GVHDの診断や病態だけでなく治療効果と予後に関連した新規バイオマーカーを報告した。慢性GVHDの治療効果を予測するバイオマーカーの報告は現在限られており、貴重な学術成果が得られたものと考えられる。将来治療への応用が進めば、治療成績の向上につながる可能性があり、社会的意義は大きい。また、移植後の長期生存の妨げとなる二次がんのうち、固形がんと骨髄系腫瘍の大規模なレジストリコホート解析の結果を報告したことの意義は大きく、今後病態解明のためのゲノム解析を進める上での重要な基礎データとなる。