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Acute Leukemias

The quality of molecular response to chemotherapy is predictive for the outcome of AML1-ETO-positive AML and is independent of pretreatment risk factors

Leukemia volume 21, pages 1177–1182 (2007)Cite this article

Abstract

The outcome of 45 AML1-ETO-positive acute myeloid leukemia (AML) patients was analyzed with special emphasis on the quality of molecular response to therapy. Patients received double induction therapy, either 6-thioguanine, cytarabine, and daunorubicin (TAD9)/high-dose cytosine arabinoside plus mitoxantrone (HAM) or HAM/HAM, followed by consolidation therapy (TAD9) according to the AML-Cooperative group 92 trial (AMLCG92) and AML-Cooperative group 99 trial (AMLCG99). All cases underwent cytomorphological, cytogenetical and molecular genetic analyses. AML1-ETO transcript levels were quantitatively assessed at diagnosis and during follow-up by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The median reduction of initial AML1-ETO expression level was 4 log (range 0–5) after both induction and consolidation therapies. The quality of molecular response after induction as well as consolidation therapies had significant impact on the cumulative incidence of relapse (P=0.021 and P=0.001, respectively), event free survival (EFS: P=0.001 and P=0.001, respectively) and overall survival (OS: P=0.013 and P=0.014, respectively). HAM/HAM improved the molecular response to induction therapy (P=0.042) but after consolidation, no differences in molecular response were detectable between TAD9/HAM and HAM/HAM. Patient- or disease-related factors had no impact on the molecular response to induction or consolidation therapy. The current study demonstrates that quantification of AML1-ETO transcript levels is a powerful tool for prediction of prognosis that is independent of pretreatment risk factors, and may be helpful for directing therapeutic decisions in the future.

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Acknowledgements

We would like to thank all participants of the AMLCG study group for sending bone marrow samples to our laboratories for reference diagnosis, and for submitting clinical data, as part of the patients were treated within the AMLCG study. We thank Christina Sauerland of the Institute of Medical Informatics and Biomathematics, University of Muenster, Germany, for completing clinical data of some of the patients and Prof. Dr Torsten Haferlach of Munich Leukemia Laboratory for performing the cytomorphological analyses.

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Authors and Affiliations

  1. Department of Internal Medicine III, Ludwig-Maximilians-University Munich-Großhadern, Munich, Germany

    M Weisser & W Hiddemann

  2. Munich Leukemia Laboratory, Munich, Germany

    C Haferlach & S Schnittger

  3. Clinical Cooperative Group Acute Leukemias, GSF Research Center for Environment and Health, Neuherberg, Germany

    W Hiddemann

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  1. M Weisser
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Correspondence to M Weisser.

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Weisser, M., Haferlach, C., Hiddemann, W. et al. The quality of molecular response to chemotherapy is predictive for the outcome of AML1-ETO-positive AML and is independent of pretreatment risk factors. Leukemia 21, 1177–1182 (2007). https://doi.org/10.1038/sj.leu.2404659

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