Measurable residual disease detected by flow cytometry independently predicts prognoses of NPM1-mutated acute myeloid leukemia.

Acute myeloid leukemia (AML) with NPM1 mutation is a distinct genetic entity with favorable outcomes. Nevertheless, emerging evidence suggests that NPM1-mutated AML is still a highly heterogeneous disorder. In this study, 266 patients with AML with NPM1 mutations were retrospectively analyzed to evaluate the associations between variant allele frequency (VAF) of NPM1 mutations, co-mutated genes, measurable residual disease (MRD), and patient outcomes. Multiparameter flow cytometry (MFC) and real-time quantitative polymerase chain reaction (RT-PCR) were used for monitoring MRD. Ultimately, 106 patients were included in the long-term follow-up period. Patients with high NPM1 VAF (≥ 42.43%) had poorer 2-year relapse-free survival (RFS) (55.7% vs. 70.2%, P = 0.017) and overall survival (OS) (63.7% vs. 82.0%, P = 0.027) than those with low VAF. DNMT3A mutations negatively influenced the outcomes of patients with NPM1 mutations. Patients with high DNMT3A VAF or NPM1/DNMT3A/FLT3-ITD triple mutations had shorter RFS and significantly lower OS than that in controls. After two cycles of chemotherapy, patients with positive MFC MRD results had lower RFS (MRD+ vs. MRD-:44.9% vs. 67.6%, P = 0.007) and OS (61.5% vs. 76.6%, P = 0.011) than those without positive MFC MRD results. In multivariate analysis, high NPM1 VAF (hazard ratio [HR] = 2.045; P = 0.034) and positive MRD after two cycles of chemotherapy (HR = 3.289; P = 0.003) were independent risk factors for RFS; MRD positivity after two cycles of chemotherapy (HR = 3.293; P = 0.008) independently predicted the OS of the patients. These results indicate that VAF of both NPM1 gene itself or certain co-occurring gene pre-treatment and MRD post-treatment are potential markers for restratifying the prognoses of patients AML having NPM1 mutations.

[Clinical characteristics and therapeutic efficacy of normal karyotype AML patients with CEBPA mutation].

This study was aimed to explore the clinical characteristics and therapeutic efficacy of normal karyotype AML patients with CEBPA mutations. Fifty-five de novo AML patients with normal karyotype were retrospectively analyzed with regard to frequency of CEBPA mutation, clinical characteristics and therapeutic response. The results showed that CEBPA mutation was detected in 20 patients (36.4%), among them 17 cases displayed double mutations, three cases were with single mutation. The clinical characteristics of patients with CEBPA mutation displayed as follows: 75% of AML patients with CEBPA mutation were AML-M1 and AML-M2, the hemoglobin level at newly diagnosis was higher and the platelet count at newly diagnosis time was lower than those of AML patients without CEBPA mutation [(98.30 ± 20.33) g/L vs (81.69 ± 23.74) g/L (P < 0.05); and (33.30 ± 38.27) ×10(9)/L vs (64.79 ± 61.60) ×10(9)/L (P < 0.05)]. The leukemic cells highly expressed CD7 and CD34. The therapeutic efficacy of 1 cycle for AML patients with CEBPA mutation was satisfactory (72.2%), was higher than that of patients without CEBPA mutation(68.6%), but there was no statistical significance (P > 0.05). It is concluded that AML with CEBPA mutation is more observed in AML-M1 and AML-M2, and accompanies by high level of hemoglobin and lower platelet count, expression of CD7 and CD34. Early-term therapeutic efficacy is satisfactory. The frequency of CEBPA mutation may be higher in Chinese patients with AML compared with that reported in Western world.