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

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Posttransplantation MRD monitoring in patients with AML by next-generation sequencing using DTA and non-DTA mutations. / Heuser, Michael; Heida, Bennet; Büttner, Konstantin; Wienecke, Clara Philine; Teich, Katrin; Funke, Carolin; Brandes, Maximilian; Klement, Piroska; Liebich, Alessandro; Wichmann, Martin; Neziri, Blerina; Chaturvedi, Anuhar; Kloos, Arnold; Mintzas, Konstantinos; Gaidzik, Verena I; Paschka, Peter; Bullinger, Lars; Fiedler, Walter; Heim, Albert; Puppe, Wolfram; Krauter, Jürgen; Döhner, Konstanze; Döhner, Hartmut; Ganser, Arnold; Stadler, Michael; Hambach, Lothar; Gabdoulline, Razif; Thol, Felicitas.

in: BLOOD ADV, Jahrgang 5, Nr. 9, 11.05.2021, S. 2294-2304.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Heuser, M, Heida, B, Büttner, K, Wienecke, CP, Teich, K, Funke, C, Brandes, M, Klement, P, Liebich, A, Wichmann, M, Neziri, B, Chaturvedi, A, Kloos, A, Mintzas, K, Gaidzik, VI, Paschka, P, Bullinger, L, Fiedler, W, Heim, A, Puppe, W, Krauter, J, Döhner, K, Döhner, H, Ganser, A, Stadler, M, Hambach, L, Gabdoulline, R & Thol, F 2021, 'Posttransplantation MRD monitoring in patients with AML by next-generation sequencing using DTA and non-DTA mutations', BLOOD ADV, Jg. 5, Nr. 9, S. 2294-2304. https://doi.org/10.1182/bloodadvances.2021004367

APA

Heuser, M., Heida, B., Büttner, K., Wienecke, C. P., Teich, K., Funke, C., Brandes, M., Klement, P., Liebich, A., Wichmann, M., Neziri, B., Chaturvedi, A., Kloos, A., Mintzas, K., Gaidzik, V. I., Paschka, P., Bullinger, L., Fiedler, W., Heim, A., ... Thol, F. (2021). Posttransplantation MRD monitoring in patients with AML by next-generation sequencing using DTA and non-DTA mutations. BLOOD ADV, 5(9), 2294-2304. https://doi.org/10.1182/bloodadvances.2021004367

Vancouver

Heuser M, Heida B, Büttner K, Wienecke CP, Teich K, Funke C et al. Posttransplantation MRD monitoring in patients with AML by next-generation sequencing using DTA and non-DTA mutations. BLOOD ADV. 2021 Mai 11;5(9):2294-2304. https://doi.org/10.1182/bloodadvances.2021004367

Bibtex

@article{0b8eebbdd1ac409aa813964f4be6213d,
title = "Posttransplantation MRD monitoring in patients with AML by next-generation sequencing using DTA and non-DTA mutations",
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.",
author = "Michael Heuser and Bennet Heida and Konstantin B{\"u}ttner and Wienecke, {Clara Philine} and Katrin Teich and Carolin Funke and Maximilian Brandes and Piroska Klement and Alessandro Liebich and Martin Wichmann and Blerina Neziri and Anuhar Chaturvedi and Arnold Kloos and Konstantinos Mintzas and Gaidzik, {Verena I} and Peter Paschka and Lars Bullinger and Walter Fiedler and Albert Heim and Wolfram Puppe and J{\"u}rgen Krauter and Konstanze D{\"o}hner and Hartmut D{\"o}hner and Arnold Ganser and Michael Stadler and Lothar Hambach and Razif Gabdoulline and Felicitas Thol",
note = "{\textcopyright} 2021 by The American Society of Hematology.",
year = "2021",
month = may,
day = "11",
doi = "10.1182/bloodadvances.2021004367",
language = "English",
volume = "5",
pages = "2294--2304",
journal = "BLOOD ADV",
issn = "2473-9529",
publisher = "Elsevier BV",
number = "9",

}

RIS

TY - JOUR

T1 - Posttransplantation MRD monitoring in patients with AML by next-generation sequencing using DTA and non-DTA mutations

AU - Heuser, Michael

AU - Heida, Bennet

AU - Büttner, Konstantin

AU - Wienecke, Clara Philine

AU - Teich, Katrin

AU - Funke, Carolin

AU - Brandes, Maximilian

AU - Klement, Piroska

AU - Liebich, Alessandro

AU - Wichmann, Martin

AU - Neziri, Blerina

AU - Chaturvedi, Anuhar

AU - Kloos, Arnold

AU - Mintzas, Konstantinos

AU - Gaidzik, Verena I

AU - Paschka, Peter

AU - Bullinger, Lars

AU - Fiedler, Walter

AU - Heim, Albert

AU - Puppe, Wolfram

AU - Krauter, Jürgen

AU - Döhner, Konstanze

AU - Döhner, Hartmut

AU - Ganser, Arnold

AU - Stadler, Michael

AU - Hambach, Lothar

AU - Gabdoulline, Razif

AU - Thol, Felicitas

N1 - © 2021 by The American Society of Hematology.

PY - 2021/5/11

Y1 - 2021/5/11

N2 - 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.

AB - 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.

U2 - 10.1182/bloodadvances.2021004367

DO - 10.1182/bloodadvances.2021004367

M3 - SCORING: Journal article

C2 - 33929500

VL - 5

SP - 2294

EP - 2304

JO - BLOOD ADV

JF - BLOOD ADV

SN - 2473-9529

IS - 9

ER -