Clinical impact of measurable residual disease monitoring by ultradeep next generation sequencing in NPM1 mutated acute myeloid leukemia.

Clinical impact of measurable residual disease monitoring by ultradeep next generation sequencing in NPM1 mutated acute myeloid leukemia. Oncotarget. 2018 Nov 27;9(93):36613-36624 Authors: Patkar N, Kodgule R, Kakirde C, Raval G, Bhanshe P, Joshi S, Chaudhary S, Badrinath Y, Ghoghale S, Kadechkar S, Khizer SH, Kannan S, Shetty D, Gokarn A, Punatkar S, Jain H, Bagal B, Menon H, Sengar M, Khattry N, Tembhare P, Subramanian P, Gujral S Abstract Detection of measurable residual disease (MRD) by mutation specific techniques has prognostic relevance in NPM1 mutated AML (NPM1 mut AML). However, the clinical utility of next generation sequencing (NGS) to detect MRD in AML remains unproven. We analysed the clinical significance of monitoring MRD using ultradeep NGS (NGS-MRD) and flow cytometry (FCM-MRD) in 137 samples obtained from 83 patients of NPM1 mut AML at the end of induction (PI) and consolidation (PC). We could monitor 12 different types of NPM1 mutations at a sensitivity of 0.001% using NGS-MRD. We demonstrated a significant correlation between NGS-MRD and real time quantitative PCR (RQ-PCR). Based upon a one log reduction between PI and PC time points we could classify patients as NGS-MRD positive (<1log reduction) or negative (>1log reduction). NGS-MRD, FCM-MRD as well as DNMT3A mutations were predictive of inferior overall survival (OS) and relapse free survival (RFS). On a multivariate analysis NGS-MRD emerged as an indepe...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research