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Measurable residual disease monitoring by NGS before allogeneic hematopoietic cell transplantation in AML

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Measurable residual disease monitoring by NGS before allogeneic hematopoietic cell transplantation in AML. / Thol, Felicitas; Gabdoulline, Razif; Liebich, Alessandro; Klement, Piroska; Schiller, Johannes; Kandziora, Christian; Hambach, Lothar; Stadler, Michael; Koenecke, Christian; Flintrop, Madita; Pankratz, Mira; Wichmann, Martin; Neziri, Blerina; Büttner, Konstantin; Heida, Bennet; Klesse, Sabrina; Chaturvedi, Anuhar; Kloos, Arnold; Göhring, Gudrun; Schlegelberger, Brigitte; Gaidzik, Verena I; Bullinger, Lars; Fiedler, Walter; Heim, Albert; Hamwi, Iyas; Eder, Matthias; Krauter, Jürgen; Schlenk, Richard F; Paschka, Peter; Döhner, Konstanze; Döhner, Hartmut; Ganser, Arnold; Heuser, Michael.

In: BLOOD, Vol. 132, No. 16, 18.10.2018, p. 1703-1713.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Thol, F, Gabdoulline, R, Liebich, A, Klement, P, Schiller, J, Kandziora, C, Hambach, L, Stadler, M, Koenecke, C, Flintrop, M, Pankratz, M, Wichmann, M, Neziri, B, Büttner, K, Heida, B, Klesse, S, Chaturvedi, A, Kloos, A, Göhring, G, Schlegelberger, B, Gaidzik, VI, Bullinger, L, Fiedler, W, Heim, A, Hamwi, I, Eder, M, Krauter, J, Schlenk, RF, Paschka, P, Döhner, K, Döhner, H, Ganser, A & Heuser, M 2018, 'Measurable residual disease monitoring by NGS before allogeneic hematopoietic cell transplantation in AML', BLOOD, vol. 132, no. 16, pp. 1703-1713. https://doi.org/10.1182/blood-2018-02-829911

APA

Thol, F., Gabdoulline, R., Liebich, A., Klement, P., Schiller, J., Kandziora, C., Hambach, L., Stadler, M., Koenecke, C., Flintrop, M., Pankratz, M., Wichmann, M., Neziri, B., Büttner, K., Heida, B., Klesse, S., Chaturvedi, A., Kloos, A., Göhring, G., ... Heuser, M. (2018). Measurable residual disease monitoring by NGS before allogeneic hematopoietic cell transplantation in AML. BLOOD, 132(16), 1703-1713. https://doi.org/10.1182/blood-2018-02-829911

Vancouver

Thol F, Gabdoulline R, Liebich A, Klement P, Schiller J, Kandziora C et al. Measurable residual disease monitoring by NGS before allogeneic hematopoietic cell transplantation in AML. BLOOD. 2018 Oct 18;132(16):1703-1713. https://doi.org/10.1182/blood-2018-02-829911

Bibtex

@article{1b934932f25f42a18762d4477baa7d2b,
title = "Measurable residual disease monitoring by NGS before allogeneic hematopoietic cell transplantation in AML",
abstract = "Molecular measurable residual disease (MRD) assessment is not established in approximately 60% of acute myeloid leukemia (AML) patients because of the lack of suitable markers for quantitative real-time polymerase chain reaction. To overcome this limitation, we established an error-corrected next-generation sequencing (NGS) MRD approach that can be applied to any somatic gene mutation. The clinical significance of this approach was evaluated in 116 AML patients undergoing allogeneic hematopoietic cell transplantation (alloHCT) in complete morphologic remission (CR). Targeted resequencing at the time of diagnosis identified a suitable mutation in 93% of the patients, covering 24 different genes. MRD was measured in CR samples from peripheral blood or bone marrow before alloHCT and identified 12 patients with persistence of an ancestral clone (variant allele frequency [VAF] >5%). The remaining 96 patients formed the final cohort of which 45% were MRD+ (median VAF, 0.33%; range, 0.016%-4.91%). In competing risk analysis, cumulative incidence of relapse (CIR) was higher in MRD+ than in MRD- patients (hazard ratio [HR], 5.58; P < .001; 5-year CIR, 66% vs 17%), whereas nonrelapse mortality was not significantly different (HR, 0.60; P = .47). In multivariate analysis, MRD positivity was an independent negative predictor of CIR (HR, 5.68; P < .001), in addition to FLT3-ITD and NPM1 mutation status at the time of diagnosis, and of overall survival (HR, 3.0; P = .004), in addition to conditioning regimen and TP53 and KRAS mutation status. In conclusion, NGS-based MRD is widely applicable to AML patients, is highly predictive of relapse and survival, and may help refine transplantation and posttransplantation management in AML patients.",
keywords = "Journal Article",
author = "Felicitas Thol and Razif Gabdoulline and Alessandro Liebich and Piroska Klement and Johannes Schiller and Christian Kandziora and Lothar Hambach and Michael Stadler and Christian Koenecke and Madita Flintrop and Mira Pankratz and Martin Wichmann and Blerina Neziri and Konstantin B{\"u}ttner and Bennet Heida and Sabrina Klesse and Anuhar Chaturvedi and Arnold Kloos and Gudrun G{\"o}hring and Brigitte Schlegelberger and Gaidzik, {Verena I} and Lars Bullinger and Walter Fiedler and Albert Heim and Iyas Hamwi and Matthias Eder and J{\"u}rgen Krauter and Schlenk, {Richard F} and Peter Paschka and Konstanze D{\"o}hner and Hartmut D{\"o}hner and Arnold Ganser and Michael Heuser",
note = "{\textcopyright} 2018 by The American Society of Hematology.",
year = "2018",
month = oct,
day = "18",
doi = "10.1182/blood-2018-02-829911",
language = "English",
volume = "132",
pages = "1703--1713",
journal = "BLOOD",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "16",

}

RIS

TY - JOUR

T1 - Measurable residual disease monitoring by NGS before allogeneic hematopoietic cell transplantation in AML

AU - Thol, Felicitas

AU - Gabdoulline, Razif

AU - Liebich, Alessandro

AU - Klement, Piroska

AU - Schiller, Johannes

AU - Kandziora, Christian

AU - Hambach, Lothar

AU - Stadler, Michael

AU - Koenecke, Christian

AU - Flintrop, Madita

AU - Pankratz, Mira

AU - Wichmann, Martin

AU - Neziri, Blerina

AU - Büttner, Konstantin

AU - Heida, Bennet

AU - Klesse, Sabrina

AU - Chaturvedi, Anuhar

AU - Kloos, Arnold

AU - Göhring, Gudrun

AU - Schlegelberger, Brigitte

AU - Gaidzik, Verena I

AU - Bullinger, Lars

AU - Fiedler, Walter

AU - Heim, Albert

AU - Hamwi, Iyas

AU - Eder, Matthias

AU - Krauter, Jürgen

AU - Schlenk, Richard F

AU - Paschka, Peter

AU - Döhner, Konstanze

AU - Döhner, Hartmut

AU - Ganser, Arnold

AU - Heuser, Michael

N1 - © 2018 by The American Society of Hematology.

PY - 2018/10/18

Y1 - 2018/10/18

N2 - Molecular measurable residual disease (MRD) assessment is not established in approximately 60% of acute myeloid leukemia (AML) patients because of the lack of suitable markers for quantitative real-time polymerase chain reaction. To overcome this limitation, we established an error-corrected next-generation sequencing (NGS) MRD approach that can be applied to any somatic gene mutation. The clinical significance of this approach was evaluated in 116 AML patients undergoing allogeneic hematopoietic cell transplantation (alloHCT) in complete morphologic remission (CR). Targeted resequencing at the time of diagnosis identified a suitable mutation in 93% of the patients, covering 24 different genes. MRD was measured in CR samples from peripheral blood or bone marrow before alloHCT and identified 12 patients with persistence of an ancestral clone (variant allele frequency [VAF] >5%). The remaining 96 patients formed the final cohort of which 45% were MRD+ (median VAF, 0.33%; range, 0.016%-4.91%). In competing risk analysis, cumulative incidence of relapse (CIR) was higher in MRD+ than in MRD- patients (hazard ratio [HR], 5.58; P < .001; 5-year CIR, 66% vs 17%), whereas nonrelapse mortality was not significantly different (HR, 0.60; P = .47). In multivariate analysis, MRD positivity was an independent negative predictor of CIR (HR, 5.68; P < .001), in addition to FLT3-ITD and NPM1 mutation status at the time of diagnosis, and of overall survival (HR, 3.0; P = .004), in addition to conditioning regimen and TP53 and KRAS mutation status. In conclusion, NGS-based MRD is widely applicable to AML patients, is highly predictive of relapse and survival, and may help refine transplantation and posttransplantation management in AML patients.

AB - Molecular measurable residual disease (MRD) assessment is not established in approximately 60% of acute myeloid leukemia (AML) patients because of the lack of suitable markers for quantitative real-time polymerase chain reaction. To overcome this limitation, we established an error-corrected next-generation sequencing (NGS) MRD approach that can be applied to any somatic gene mutation. The clinical significance of this approach was evaluated in 116 AML patients undergoing allogeneic hematopoietic cell transplantation (alloHCT) in complete morphologic remission (CR). Targeted resequencing at the time of diagnosis identified a suitable mutation in 93% of the patients, covering 24 different genes. MRD was measured in CR samples from peripheral blood or bone marrow before alloHCT and identified 12 patients with persistence of an ancestral clone (variant allele frequency [VAF] >5%). The remaining 96 patients formed the final cohort of which 45% were MRD+ (median VAF, 0.33%; range, 0.016%-4.91%). In competing risk analysis, cumulative incidence of relapse (CIR) was higher in MRD+ than in MRD- patients (hazard ratio [HR], 5.58; P < .001; 5-year CIR, 66% vs 17%), whereas nonrelapse mortality was not significantly different (HR, 0.60; P = .47). In multivariate analysis, MRD positivity was an independent negative predictor of CIR (HR, 5.68; P < .001), in addition to FLT3-ITD and NPM1 mutation status at the time of diagnosis, and of overall survival (HR, 3.0; P = .004), in addition to conditioning regimen and TP53 and KRAS mutation status. In conclusion, NGS-based MRD is widely applicable to AML patients, is highly predictive of relapse and survival, and may help refine transplantation and posttransplantation management in AML patients.

KW - Journal Article

U2 - 10.1182/blood-2018-02-829911

DO - 10.1182/blood-2018-02-829911

M3 - SCORING: Journal article

C2 - 30190321

VL - 132

SP - 1703

EP - 1713

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 16

ER -