Department of Hematology, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China (mainland).
School of Medicine, Nankai University, Tianjin, China (mainland).
Ann Transplant. 2024 Jul 2;29:e943688. doi: 10.12659/AOT.943688.
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.
自下一代测序(NGS)技术广泛应用以来,人们对克隆性造血(CH)相关基因突变与异基因造血干细胞移植(allo-HSCT)之间的关系进行了广泛研究。然而,研究主要集中在供体 CH 突变与移植预后之间的关系,而关于受者 CH 突变与急性移植物抗宿主病(aGVHD)之间的关系的研究则较少。
我们分析了 196 例接受 allo-HSCT 的 AML 患者的 NGS 结果及其与 aGVHD 和预后的相关性。
共有 93 例(47.4%)患者存在 CH 突变。最常突变的基因是 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 aGVHD 发生率更高。年龄大于 45 岁接受 allo-HSCT 的患者中,DNMT3A 突变而非 TET2 或 ASXL1 突变是 aGVHD 的独立危险因素。中位随访 42.7 个月后,CH 突变与总生存和无白血病生存无关。
DNMT3A 突变而非 TET2 或 ASXL1 突变与更高的 aGVHD 发生率相关。