Next-Generation Sequencing (Ngs) Panel Fails To Predict Overall Survival (Os) And Disease-Free Survival (Dfs) In A Cohort Of Peruvian Patients With Acute Myeloid Leukemia (Aml)

Context: AML represents a broad and complex group of diseases characterized by involvement of the myeloid lineage on hematopoiesis. Objective: To explore the frequency and impact of mutated genes on clinical outcomes in a cohort of Peruvian patients. Design: In this report, we showed 32 AML cases treated at 3 medical centers in Lima (Clinica Delgado, Anglo Americana, and INEN) from January 2016 until May 2021. Setting: Information at diagnosis was clinical, karyotype, molecular PCR panel, myeloid NGS panel, therapy regimen, response to treatment, DFS, and OS Patients or Other Participants: A total of 32 cases were studied. F/M=0.6 (12/20), median age 55 years (32–87). Interventions: Among the 24 available karyotypes, the abnormal vs diploid karyotype ratio was 0.26 (5/19). Number of pathogenic mutated genes was 2.5 (range 0–10). Most common (≥15%) pathogenic mutated genes were BCOR (n=7, 21.9%), CUX1 (n=5, 15.6%), DNMT3 (n=8, 25.0%), and NRAS (n=5, 15.6%). Main Outcome Measures: Response rates were as follows: 71.9% complete (23/32), 18.8% non-response (6/32), and 9.3% non-evaluable (3/32). The estimated median OS was 26.01 months for the entire cohort, the 1- and 2-year OS were 72.1% and 51.1%, respectively. The estimated median DFS was 15.79 months for the entire cohort, the 1- and 2-year DFS were 77.6% and 31.5%, respectively. Mutated TP53 was detected in 3 cases, with no therapeutic response in 2 of them. Results: No significant difference in OS was observed in cases with ≥3 pathogenic mutated genes (log-rank 0.10, p=0.920) or ≥3 pathogenic mutated genes + TP53 cases (log-rank 0.11 p=0.739). No significant difference in DFS was observed in cases ≥3 pathogenic mutated genes + TP53 cases (log-rank 0.775 p=0.379). Conclusions: Of 53 genes, four genes were detected in ≥ 15% of cases: BCOR, CUX1, DNMT3, and NRAS. TP53 was related to a high degree of therapeutic failure response and short OS. Number of pathogenic mutated genes ≥3 or ≥4 by NGS showed no significant tendency toward shorter OS. A composite analysis of patients with 4 mutated genes with or without mutated-TP53 showed no significantly shorter OS and DFS. Further studies with mature data and more cases are warranted to propose risk stratification by NGS.