1. ¹Department of Internal Medicine III, Ludwig-Maximilians-University Munich-Grohadern, Munich, Germany
2. ²Munich Leukemia Laboratory, Munich, Germany
3. ³Clinical Cooperative Group Acute Leukemias, GSF Research Center for Environment and Health, Neuherberg, Germany

Correspondence: Dr M Weisser, Department of Internal Medicine III, Klinikum Grosshadern, Ludwig-Maximilians-University Munich-Grohadern, Marchionini Street 15, Munich 81377, Germany. E-mail: martin.weisser@gmx.de

Received 9 February 2007; Accepted 16 February 2007; Published online 22 March 2007.

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.