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, Jahrgang 132, Nr. 16, 18.10.2018, S. 1703-1713.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -