Prognostic Value of Molecular and Clinical Features in Patients with NPM1 Gene Mutation in Acute Myeloid Leukemia.

Background: Nucleophosmin 1 (NPM1) mutations represent one of the most frequent genetic alterations in acute myeloid leukemia (AML). However, the prognostic significance of concurrent molecular abnormalities and clinical features in NPM1-mutated AML remains to be fully elucidated.

Methods: We retrospectively analyzed 73 adult AML patients with NPM1 mutations. Clinical characteristics, molecular features, and treatment outcomes were evaluated. Comprehensive molecular profiling was performed to detect concurrent mutations. Survival analysis included recurrence-free survival (RFS) and overall survival (OS), with multivariate analysis to identify independent prognostic factors.

Results: The cohort showed a female predominance (54.8%), with a median age of 53.1 years. FLT3-ITD mutations were detected in 49.3% of patients, followed by DNMT3A (42.5%) and IDH1 (23.3%) mutations. Significant differences across FAB subtypes were observed in blast percentage (p = 0.003), WBC count (p = 0.013), and platelet count (p = 0.004). Multivariate analysis identified elevated WBC count (HR = 1.01, p = 0.008), increased LDH levels (HR = 1.0, p = 0.006), and FLT3-ITD mutations (HR = 2.55, p = 0.007) as independent adverse factors for RFS. For OS, low albumin levels (HR = 0.89, p = 0.017), DNMT3A mutations (HR = 2.49, p = 0.042), and treatment response were significant prognostic factors, while allogeneic hematopoietic stem cell transplantation showed a protective effect (HR = 0.08, p = 0.015).

Conclusions: Our findings demonstrate that the clinical outcomes of NPM1-mutated AML are significantly influenced by concurrent molecular mutations and clinical parameters. The presence of FLT3-ITD and DNMT3A mutations, along with specific clinical features, identifies patients with adverse prognosis who might benefit from more intensive therapeutic strategies, including allogeneic transplantation.