Clonal Hematopoiesis-Associated Gene Mutations Affect Acute Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation in AML Patients.

IF 1.1 4区 医学 Q3 SURGERY Annals of Transplantation Pub Date : 2024-07-02 DOI:10.12659/AOT.943688
Xiaoxuan Wei, Sai Huang, Zhenyang Gu, Jing Liu, Meng Li, Xiangshu Jin, Jian Bo, Fei Li, Yu Jing, Xiaoning Gao, Liping Dou, Daihong Liu, Chunji Gao
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Abstract

BACKGROUND The relationship between clonal hematopoiesis (CH)-associated gene mutations and allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been extensively studied since next-generation sequencing (NGS) technology became widely available. However, research has mainly focused on the relationship between donor CH mutations and transplant prognosis, and research into the relationship between CH mutations in the recipient and acute graft-versus-host disease (aGVHD) is lacking. MATERIAL AND METHODS We analyzed NGS results and their correlation with aGVHD and prognosis in 196 AML patients undergoing allo-HSCT. RESULTS A total of 93 (47.4%) patients had CH mutations. The most frequently mutated genes were DNMT3A (28 of 196; 14.3%), TET2 (22 of 196; 11.2%), IDH1 (15 of 196; 7.7%), IDH2 (14 of 196; 7.1%), and ASXL1 (13 of 196; 6.6%). The incidence of aGVHD was higher in patients older than 45 years old with DTA mutations (DNMT3A, TET2 or ASXL1). DNMT3A mutation but not with TET2 or ASXL1 mutation was an independent risk factor for aGVHD in patients receiving allo-HSCT older than 45 years old. With a median follow-up of 42.7 months, CH mutations were not associated with overall survival and leukemia-free survival. CONCLUSIONS DNMT3A mutation, but not TET2 or ASXL1 mutation, was associated with higher incidence of aGVHD.

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克隆造血相关基因突变影响急性髓细胞性白血病患者造血干细胞移植后的急性移植物抗宿主疾病
背景自下一代测序(NGS)技术广泛应用以来,克隆造血(CH)相关基因突变与异基因造血干细胞移植(allo-HSCT)之间的关系已得到广泛研究。然而,研究主要集中在供者CH基因突变与移植预后之间的关系,而对受者CH基因突变与急性移植物抗宿主病(aGVHD)之间关系的研究还很缺乏。材料与方法 我们分析了 196 例接受异体 HSCT 的 AML 患者的 NGS 结果及其与 aGVHD 和预后的相关性。结果 共有 93 例(47.4%)患者出现 CH 基因突变。最常见的突变基因是 DNMT3A(196 例中有 28 例;14.3%)、TET2(196 例中有 22 例;11.2%)、IDH1(196 例中有 15 例;7.7%)、IDH2(196 例中有 14 例;7.1%)和 ASXL1(196 例中有 13 例;6.6%)。年龄大于 45 岁且存在 DTA 突变(DNMT3A、TET2 或 ASXL1)的患者发生 aGVHD 的几率更高。在接受allo-HSCT的45岁以上患者中,DNMT3A突变而非TET2或ASXL1突变是发生aGVHD的独立危险因素。中位随访时间为42.7个月,CH突变与总生存期和无白血病生存期无关。结论 DNMT3A 突变与较高的 aGVHD 发生率有关,而 TET2 或 ASXL1 突变与较高的 aGVHD 发生率无关。
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来源期刊
CiteScore
2.50
自引率
0.00%
发文量
79
审稿时长
>12 weeks
期刊介绍: Annals of Transplantation is one of the fast-developing journals open to all scientists and fields of transplant medicine and related research. The journal is published quarterly and provides extensive coverage of the most important advances in transplantation. Using an electronic on-line submission and peer review tracking system, Annals of Transplantation is committed to rapid review and publication. The average time to first decision is around 3-4 weeks. Time to publication of accepted manuscripts continues to be shortened, with the Editorial team committed to a goal of 3 months from acceptance to publication. Expert reseachers and clinicians from around the world contribute original Articles, Review Papers, Case Reports and Special Reports in every pertinent specialty, providing a lot of arguments for discussion of exciting developments and controversies in the field.
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