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

NPM1突变型急性髓系白血病完全分子缓解时克隆性造血突变的预后影响

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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 × 10(9)/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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