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Hubmann, M.* ; Köhnke, T.* ; Hoster, E.* ; Schneider, S.* ; Dufour, A.* ; Zellmeier, E.* ; Fiegl, M.* ; Braess, J.* ; Bohlander, S.K.* ; Subklewe, M. ; Sauerland, M.C.* ; Berdel, W.E.* ; Büchner, T.* ; Wörmann, B.* ; Hiddemann, W.* ; Spiekermann, K.

Molecular response assessment by quantitativerael-time polymerase chain reaction after induction therapy in NPM1-mutated patients identifies patients at high risk for relapse.

Haematologica 99, 1317-1325 (2014)
Verlagsversion Postprint Post-Print DOI PMC
Open Access Gold
Monitoring of minimal residual disease represents an important diagnostic tool to identify patients with acute myeloid leukemia at high risk for relapse. In this study the prognostic potential of minimal residual disease monitoring by quantitative real-time PCR of NPM1 mutations of patients treated in the AMLCG trials 1999, 2004 and 2008 was investigated. Minimal residual disease monitoring was performed in 588 samples of 158 NPM1 mutation A, B and D positive patients at diagnosis, in aplasia, after induction therapy, after consolidation therapy, and during follow-up with a sensitivity of 10-6. 127 patients (80.4%) achieved complete remission after induction therapy and of these 56 patients (44.1%) relapsed. At each checkpoints, minimal residual disease cut-offs were calculated. After induction therapy a cut-off NPM1 mutation ratio of 0.01 revealed a high hazard ratio of 4.26 and the highest sensitivity of 76% for the prediction of relapse. This was reflected in a cumulative incidence of relapse after 2 years of 77.8% for cut-off positive patients versus 26.4% for cut-off negative patients, respectively. In the favorable subgroup according to European LeukemiaNet, the cut-off after induction therapy also separates the cohort into two prognostic groups with a cumulative incidence of relapse of 76% versus 6% after 2 years. Our data demonstrate that in addition to pre-therapeutic factors, the individual minimal residual disease course is an important prognostic factor and could be included into clinical trials for the guidance of postremission therapy. Trials were registered at www.clinicaltrials.gov (#NCT01382147, #NCT00266136) and at the European Leukemia Trial Registry (#LN_AMLINT2004_230).
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Acute Myeloid Leukemia ; Mrd ; Minimal Residual Disease ; Npm1 ; Rt-pcr; Acute Myeloid-leukemia; Minimal Residual Disease; High-dose Cytarabine; Acute Myelogenous Leukemia; Normal Karyotype; European Leukemianet; Prognostic Impact; Clonal Evolution; Npm1 Mutations; Gene-mutations
ISSN (print) / ISBN 0390-6078
e-ISSN 1592-8721
Zeitschrift Haematologica - The Hematology Journal
Quellenangaben Band: 99, Heft: 8, Seiten: 1317-1325 Artikelnummer: , Supplement: ,
Verlag Ferrata Storti Foundation
Verlagsort Pavia
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) CCG Hematopoetic Cell Transplants (IMI-KHZ)
CCG Pathogenesis of Acute Myeloid Leukemia (KKG-KPL)