• Jan Krönke, Richard F Schlenk, Kai-Ole Jensen, Florian Tschürtz, Andrea Corbacioglu, Verena I Gaidzik, Peter Paschka, Shiva Onken, Karina Eiwen, Marianne Habdank, Daniela Späth, Michael Lübbert, Mohammed Wattad, Thomas Kindler, Helmut R Salih, Gerhard Held, David Nachbaur, Marie von Lilienfeld-Toal, Ulrich Germing, Detlef Haase, Hans-Günther Mergenthaler, Jürgen Krauter, Arnold Ganser, Gudrun Göhring, Brigitte Schlegelberger, Hartmut Döhner, and Konstanze Döhner.
• Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
• J. Clin. Oncol. 2011 Jul 1; 29 (19): 2709-16.

PurposeTo evaluate the prognostic value of minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) with NPM1 mutation (NPM1(mut)).Patients And MethodRNA-based real-time quantitative polymerase chain reaction (RQ-PCR) specific for the detection of six different NPM1(mut) types was applied to 1,682 samples (bone marrow, n = 1,272; blood, n = 410) serially obtained from 245 intensively treated younger adult patients who were 16 to 60 years old.ResultsNPM1(mut) transcript levels as a continuous variable were significantly associated with prognosis after each treatment cycle. Achievement of RQ-PCR negativity after double induction therapy identified patients with a low cumulative incidence of relapse (CIR; 6.5% after 4 years) compared with RQ-PCR-positive patients (53.0%; P < .001); this translated into significant differences in overall survival (90% v 51%, respectively; P = .001). After completion of therapy, CIR was 15.7% in RQ-PCR-negative patients compared with 66.5% in RQ-PCR-positive patients (P < .001). Multivariable analyses after double induction and after completion of consolidation therapy revealed higher NPM1(mut) transcript levels as a significant factor for a higher risk of relapse and death. Serial post-treatment assessment of MRD allowed early detection of relapse in patients exceeding more than 200 NPM1(mut)/10(4) ABL copies.ConclusionWe defined clinically relevant time points for NPM1(mut) MRD assessment that allow for the identification of patients with AML who are at high risk of relapse. Monitoring of NPM1(mut) transcript levels should be incorporated in future clinical trials to guide therapeutic decisions.

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