Prognostic impact of clonal hematopoiesis mutations at complete molecular remission in acute myeloid leukemia with NPM1 mutation.

IF 2.7 3区 医学 Q3 ONCOLOGY Journal of Cancer Research and Clinical Oncology Pub Date : 2024-10-18 DOI:10.1007/s00432-024-05999-6
Linlin Wang, Mingkai Shu, Zhibo Zhang, Xueqing Dou, Xiaoyu Xu, Yanan Ma, Lijun Wen, Xiaofei Yang, Suning Chen
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Abstract

The prognostic impact of clonal hematopoiesis (CH) in complete molecular remission (CMR) in acute myeloid leukemia (AML) remains controversial. Here, we explored the prognosis of CH-related gene mutations (CH-mutation) at CMR in patients with AML with NPM1 mutation (NPM1c AML). Ninety-one patients with de novo NPM1c AML were included between June 2018 and June 2023, including 32 patients with CH-related mutation at CMR and 59 patients without. A cutoff of ≥ 2.0% for variant allele frequency (VAF) of residual mutations was used to define CH-mutation at CMR. Thirty-two patients with CH-mutation at CMR had a greater median age and higher white blood cell (WBC) counts than those without (median age, 50.5 and 45 years, respectively; p = 0.028 and WBC count: 34.5 and 10 × 109/l, respectively; p = 0.004). The incidence of DNMT3A and TET2 mutations before treatment was higher in the group with CH-mutations at CMR compared to the one without (71.9% vs. 13.6%, and 21.9% vs. 6.8%, respectively). Notably, all patients did not carry any CH of oncogenic potential (CHOP)-like mutations in CMR. There was no significant difference in event-free survival (EFS) or overall survival (OS) between the patients with and without CH-mutations at CMR or between the patients without allogeneic hematopoietic stem cell transplantation (allo-HSCT) of the two groups. In conclusion, our results suggested that CH-mutations probably did not have prognostic significance in patients with NPM1c AML who achieved CMR, and may be inappropriately for MRD monitoring.

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NPM1突变的急性髓性白血病患者完全分子缓解时克隆造血突变的预后影响
急性髓性白血病(AML)完全分子缓解(CMR)时克隆性造血(CH)对预后的影响仍存在争议。在此,我们探讨了NPM1基因突变的急性髓性白血病(NPM1c AML)患者CMR时CH相关基因突变(CH突变)的预后。研究纳入了2018年6月至2023年6月间91例新发NPM1c AML患者,其中包括32例CMR检查发现CH相关基因突变的患者和59例未发现CH相关基因突变的患者。以残留突变的变异等位基因频率(VAF)≥2.0%为临界值来定义CMR的CH突变。32名在CMR检查中发现CH突变的患者与未发现CH突变的患者相比,中位年龄更大,白细胞(WBC)计数更高(中位年龄分别为50.5岁和45岁;P = 0.028,WBC计数分别为34.5×109/L和10×109/L):分别为 34.5 和 10 × 109/l;p = 0.004)。在治疗前,CMR检查发现有CH突变的组别中,DNMT3A和TET2突变的发生率高于没有CH突变的组别(分别为71.9%对13.6%和21.9%对6.8%)。值得注意的是,所有患者在CMR中均未携带任何类似CH的致癌突变(CHOP)。在CMR有CH突变和无CH突变的患者之间,以及两组未进行异基因造血干细胞移植(allo-HSCT)的患者之间,无事件生存期(EFS)和总生存期(OS)均无明显差异。总之,我们的研究结果表明,CH突变在接受CMR检查的NPM1c AML患者中可能没有预后意义,而且可能不适合用于MRD监测。
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来源期刊
CiteScore
4.00
自引率
2.80%
发文量
577
审稿时长
2 months
期刊介绍: The "Journal of Cancer Research and Clinical Oncology" publishes significant and up-to-date articles within the fields of experimental and clinical oncology. The journal, which is chiefly devoted to Original papers, also includes Reviews as well as Editorials and Guest editorials on current, controversial topics. The section Letters to the editors provides a forum for a rapid exchange of comments and information concerning previously published papers and topics of current interest. Meeting reports provide current information on the latest results presented at important congresses. The following fields are covered: carcinogenesis - etiology, mechanisms; molecular biology; recent developments in tumor therapy; general diagnosis; laboratory diagnosis; diagnostic and experimental pathology; oncologic surgery; and epidemiology.
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