National Clinical Research Center for Hematologic Diseases, Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Yancheng No.1 People's Hospital, Affiliated Hospital of Medical School, Nanjing University, Yancheng Clinical College of Xuzhou Medical University, Yancheng, China.
J Cancer Res Clin Oncol. 2024 Oct 18;150(10):465. doi: 10.1007/s00432-024-05999-6.
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 × 10/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.
在急性髓系白血病(AML)完全分子缓解(CMR)中,克隆性造血(CH)的预后影响仍存在争议。在这里,我们研究了伴有 NPM1 突变(NPM1c AML)的 AML 患者在 CMR 时 CH 相关基因突变(CH-mutation)的预后。纳入了 2018 年 6 月至 2023 年 6 月期间 91 例初治 NPM1c AML 患者,其中 32 例患者在 CMR 时存在 CH 相关突变,59 例患者不存在。残留突变的等位基因变异频率(VAF)≥2.0%定义为 CMR 时的 CH 突变。32 例在 CMR 时存在 CH 突变的患者年龄中位数和白细胞计数(WBC)均高于无 CH 突变的患者(年龄中位数分别为 50.5 岁和 45 岁;p=0.028 和 WBC 计数分别为 34.5×10/l 和 10×10/l;p=0.004)。在 CMR 时存在 CH 突变的患者中,治疗前 DNMT3A 和 TET2 突变的发生率高于无 CH 突变的患者(分别为 71.9% vs. 13.6%和 21.9% vs. 6.8%)。值得注意的是,所有患者在 CMR 时均未携带任何 CH 样致瘤性突变(CHOP-like mutations)。CMR 时存在或不存在 CH 突变或两组中均未行异基因造血干细胞移植(allo-HSCT)的患者之间,无事件生存(EFS)或总生存(OS)无显著差异。总之,我们的结果表明,在达到 CMR 的 NPM1c AML 患者中,CH 突变可能没有预后意义,可能不适合用于 MRD 监测。