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Blood, 15 November 2004, Vol. 104, No. 10, pp. 3078-3085.
Prepublished online as a Blood First Edition Paper on July 29, 2004; DOI 10.1182/blood-2004-03-1036.


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Submitted March 18, 2004
Accepted July 13, 2004

Determination of relapse risk based on assessment of minimal residual disease during complete remission by multiparameter flow cytometry in unselected patients with acute myeloid leukemia

Wolfgang Kern*, Daniela Voskova, Claudia Schoch, Wolfgang Hiddemann, Susanne Schnittger, and Torsten Haferlach

Laboratory for Leukemia Diagnostics, Dept. of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, Muenchen, Germany

* Corresponding author; email: Wolfgang.Kern{at}med.uni-muenchen.de.

Quantification of minimal residual disease (MRD) reveals significant prognostic information in patients treated for acute myeloid leukemia (AML). The application of multiparameter flow cytometry (MFC) for MRD assessment has resulted in significant prognostic information in selected cases in previous analyses. We analyzed MRD in unselected patients with AML in complete remission (CR) after induction (n=58) and consolidation (n=62) therapies. By using a comprehensive panel of monoclonal antibodies we identified at least one leukemia-associated aberrant immunophenotype (LAIP) in each patient. The degree of reduction between diagnosis and CR in LAIP-positive cells (log-difference, LD) as a continuous variable was significantly related to relapse-free survival (RFS) both after induction (p=0.0001) and consolidation (0.00008) therapies, respectively. The LD determined after consolidation therapy was the only parameter related to overall survival (OS; p=0.005). Separation of patients based on the 75-percentile of LD after consolidation therapy resulted in groups with highly different RFS (83.3% vs. 25.7%, p=0.0034) and OS (87.5% vs. 51.4%, p=0.0507) at two years. Multivariate analysis identified LD as independent prognostic factor for RFS at both checkpoints. MFC-based quantification of MRD reveals important prognostic information in unselected patients with AML in addition to cytogenetics and should be further evaluated and used in clinical trials.


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