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Prognostic Value of Minimal Residual Disease Quantification by Real-Time Reverse Transcriptase Polymerase Chain Reaction in Patients With Core Binding Factor Leukemias

Jürgen Krauter, Kerstin Görlich, Oliver Ottmann, Michael Lübbert, Hartmut Döhner, Wolfgang Heit, Lothar Kanz, Arnold Ganser, Gerhard Heil

From the Department of Hematology/Oncology, Hannover Medical School, Hannover; Department of Internal Medicine III, University of Frankfurt, Frankfurt; Department of Internal Medicine I, University of Freiburg, Freiburg; Department of Internal Medicine III, University of Ulm, Ulm; Department of Hematology/Oncology, Ev. Krankenhaus Essen-Werden, Essen; and Department of Internal Medicine II, University of Tübingen, Tübingen, Germany.

Address reprint requests to Jürgen Krauter, MD, Department of Hematology/Oncology, Hannover Medical School, Carl-Neuberg-Str 1, D-30625 Hannover, Germany; e-mail: krauter.juergen{at}mh-hannover.de.

Purpose: In patients with acute myeloblastic leukemia with t(8;21) or inv(16) aberrations (core binding factor [CBF] leukemias), minimal residual disease (MRD) can be sensitively detected during and after chemotherapy by use of molecular methods. However, the prognostic impact of qualitative MRD detection is still under debate. In this study, the prognostic value of MRD quantification in patients with CBF leukemias was assessed.

Patients and Methods: We quantified MRD at various time points during and after therapy by real-time reverse transcriptase polymerase chain reaction (RT-PCR) for AML1/MTG8 and CBFB/MYH11 in 37 patients with CBF leukemias treated within a multicenter trial.

Results: At initial diagnosis, the patients showed a heterogenous fusion gene expression relative to glyceraldehyde 3-phosphate dehydrogenase with a variation of more than two log steps. According to MRD status during/after therapy, two groups of patients were separated. Of the 26 patients who had MRD levels of less than 1% in relation to initial diagnosis at all time points tested after induction chemotherapy, only two experienced relapse after a median follow-up of 19 months. Of the 11 patients who had a sample with an MRD level 1% at least at one time point after induction therapy, 10 experienced relapse, with a median remission duration of 10 months (P < .001). The median interval between the informative MRD sample and clinical relapse in these patients was 3 months.

Conclusion: MRD quantification by real-time RT-PCR allows the identification of patients with a high risk of relapse among the CBF leukemias.

Supported by a grant from the Deutsche José Carreras Leukämie-Stiftung e.V., Munich; (DJCLS-R01/08) and the Kompetenznetz Akute und chronische Leukämien, funded by the German Bundesministerium für Bildung und Forschung, Berlin, Germany.

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