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Prepublished online as a Blood First Edition Paper on July 3, 2003; DOI 10.1182/blood-2003-03-0880.

Submitted March 25, 2003
Accepted June 6, 2003
New score predicting for prognosis in PML-RARA-, AML1-ETO-, or CBFB-MYH11- positive acute myeloid leukemia based on quantification of fusion transcripts
Susanne Schnittger*, Martin Weisser, Claudia Schoch, Wolfgang Hiddemann, Torsten Haferlach, and Wolfgang Kern
Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, Ludwig-Maximilians University of Muncih, University Hospital Grosshadern, Munich, Germany
Clinical Cooperative Group Leukemia (GSF), National Research Centre for Environment and Health, Munich, Germany
* Corresponding author; email: susanne.schnittger{at}med3.med.uni-muenchen.de.
To evaluate the prognostic significance of quantitative PML-RARA-, AML1-ETO- and CBFB-MYH11-fusion transcripts expression real time PCR was used to analyze bone marrow samples of 349 such patients at diagnosis and 522 samples of 142 patients also during therapy (total analyses: n=859; median number of follow-up samples: 4 per patient; median duration of assessment: 12 months). Lower expression levels at diagnosis correlated with better overall and event free survival in all three leukemia subtypes. Combining the median expression ratio after consolidation therapy and the 75%-percentile of the expression ratio at diagnosis a new score was established that separates a group with 100% EFS from a significantly worse group (p<0.0001) in each of the three AML subgroups. Eight patients showed increasing levels of expression during follow up and all relapsed. In conclusion, patients at high risk of treatment failure can be identified by 1) high levels of fusion gene expression at diagnosis and /or 2) less than 3 logs of tumor reduction during the first 3-4 months of therapy. By the combination of the transcription ratios at these two checkpoints a new powerful prognostic score has been established.

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