Clonal Hematopoiesis in Long-term Survivors after Allogeneic Stem Cell Transplantation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17848
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Tokyo Metropolitan Komagome Hospital (Clinical research laboratory)
• Principal Investigator: Toya Takashi 東京都立駒込病院(臨床研究室), 血液内科, 医員 (40732805)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: クローン性造血 / 同種造血幹細胞移植

Outline of Final Research Achievements

101 patients who survived without relapse at least 10 years after allogeneic SCT were included. PB samples were collected and targeted sequencing was done. Calculated copy number variations (CNVs) were statistically evaluated based on the NGS data.
Median interval from SCT to sampling was 13.8 years. 44 gene mutations and 5 CNVs were detected in 34 patients (33.7%). DNMT3A was most common (26.5%). CH was frequent when both the patient and the donor were old. Multivariate analysis showed that Higher donor age and CML were associated with CH. Mutations in samples collected 28 days after SCT were also assessed in 12 CH-positive patients. Among 17 CHs, 4 were also detected in day-28 samples, but others were newly detected in 10-year. RDW in 10-year sample was higher in patients with CH in day-28 sample.
In conclusion, CH was common after SCT, especially in patients with CML. Both of donor/recipient age was important. Some CHs were derived from donor; others seemed to be achieved after SCT.

Free Research Field

造血幹細胞移植

Academic Significance and Societal Importance of the Research Achievements

同種造血幹細胞移植後長期生存者でクローン性造血が高頻度に認められることを明らかにした。ドナー由来造血細胞のCHの有無に患者年齢や基礎疾患との関係が見られたことは、骨髄微小環境の関与を示唆するものと考えられた。
がんや心血管イベントは移植後晩期合併症としてしばしば認められ長期生存の障壁となりうるが、一方でこれらの疾患はクローン性造血とも関連があることが知られている。移植患者のクローン性造血の有無を調べることでこれら晩期合併症の発症予測や予防、移植患者の長期予後改善に資する可能性があるが、今後前方視的解析を行うことでより明確な結果を出すことが必要である。