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Posttransplantation MRD monitoring in patients with AML by next-generation sequencing using DTA and non-DTA mutations

Item Type:Article
Title:Posttransplantation MRD monitoring in patients with AML by next-generation sequencing using DTA and non-DTA mutations
Creators Name:Heuser, M. and Heida, B. and Büttner, K. and Wienecke, C.P. and Teich, K. and Funke, C. and Brandes, M. and Klement, P. and Liebich, A. and Wichmann, M. and Neziri, B. and Chaturvedi, A. and Kloos, A. and Mintzas, K. and Gaidzik, V.I. and Paschka, P. and Bullinger, L. and Fiedler, W. and Heim, A. and Puppe, W. and Krauter, J. and Döhner, K. and Döhner, H. and Ganser, A. and Stadler, M. and Hambach, L. and Gabdoulline, R. and Thol, F.
Abstract:Next-generation sequencing (NGS)-based measurable residual disease (MRD) monitoring in patients with acute myeloid leukemia (AML) is widely applicable and prognostic prior to allogeneic hematopoietic cell transplantation (alloHCT). We evaluated the prognostic role of clonal hematopoiesis-associated DNMT3A, TET2, and ASXL1 (DTA) and non-DTA mutations for MRD monitoring post-alloHCT to refine MRD marker selection. Of 154 patients with AML, 138 (90%) had at least one mutation at diagnosis, which were retrospectively monitored by amplicon-based error-corrected NGS on day 90 and/or day 180 post-alloHCT. MRD was detected in 34 patients on day 90 and/or day 180 (25%). The rate of MRD positivity was similar when DTA and non-DTA mutations were considered separately (17.6% vs 19.8%). DTA mutations had no prognostic impact on cumulative incidence of relapse, relapse-free survival, or overall survival in our study and were removed from further analysis. In the remaining 131 patients with at least 1 non-DTA mutation, clinical and transplantation-associated characteristics were similarly distributed between MRD-positive and MRD-negative patients. In multivariate analysis, MRD positivity was an independent adverse predictor of cumulative incidence of relapse, relapse-free survival, and overall survival but not of nonrelapse mortality. The prognostic effect was independent of different cutoffs (above limit of detection, 0.1% and 1% variant allele frequency). MRD log-reduction between diagnosis and post-alloHCT assessment had no prognostic value. MRD status post-alloHCT had the strongest impact in patients who were MRD positive prior to alloHCT. In conclusion, non-DTA mutations are prognostic NGS-MRD markers post-alloHCT, whereas the prognostic role of DTA mutations in the posttransplant setting remains open.
Keywords:High-Throughput Nucleotide Sequencing, Massively-Parallel Genome Sequencing, Mutation, Transplantation, Hematopoietic Stem Cell Transplantation, Leukemia, Myelocytic, Acute, Residual Tumor
Source:Blood Advances
Publisher:American Society of Hematology
Page Range:2294-2304
Date:11 May 2021
Official Publication:https://doi.org/10.1182/bloodadvances.2021004367
PubMed:View item in PubMed

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