Monitoring of minimal residual disease in acute myeloid leukemia Monitorisierung minimaler Resterkrankung bei akuter myeloischer Leukämie

Abstract

Abstract Monitoring minimal residual disease (MRD) becomes increasingly important in the risk-adapted management of patients with acute myeloid leukemia (AML). The two most sensitive and also quantitative methods for MRD detection are multiparameter flow cytometry (MFC) and real-time PCR (QRT-PCR). Fusion gene-specific PCR in AML is based on the RNA level while MFC evaluates MRD levels based on cell counts. Both methods have been demonstrated to independently impact the patients' prognosis. The strong power of MFC has been shown mainly in the assessment of early clearance of the malignant clone. MRD levels in AML with fusion genes have the strongest prognostic power after the end of consolidation therapy. In addition, with QRT-PCR, highly predictive initial expression levels can be assessed. With both methods, early detection of relapse is possible. Today, validated PCR-based MRD is being done not only with fusion genes that are detectable in only 20–25% of all AML, but also with new molecular markers like FLT3-mutations, NPM-mutations, MLL-PTD, WT1, and EVI1 expression. Thus, in 80–90% of all AML, a marker for PCR is available that can be detected with a sensitivity of 1:10,000 to 1:1,000,000. In contrast, MFC based MRD quantification is possible in nearly 100% of all AML. However, in some cases the sensitivity is somewhat lower than with PCR. Large clinical trials will determine the role and place of immunologic and PCR-based monitoring in the prognostic stratification of patients with AML.