Minimal residual core binding factor AMLs by real time quantitative PCR—Initial response to chemotherapy predicts event free survival and close monitoring of peripheral blood unravels the kinetics of relapse

Abstract 

Minimal residual disease (MRD) was measured by RQ-PCR in 11 AML1/ETO and 13 CBFβ/MYH11 patients at diagnosis, after induction chemotherapy, and at all subsequent visits. Median detection limits were 1:50,000 and 1:10,000, respectively. In 64/103 samples MRD was detectable and highly correlated in PB and BM. In 38/103 samples, where MRD was only detectable in BM, median BM MRD was 3.5log lower than at diagnosis. Event free survival was significantly inferior in case of <2log reduction post-induction MRD. Persistent MRD was always followed by hematological relapse. Molecular progression rate in relapsing CBFβ/MYH11 was surprisingly slow with a time lag to hematological relapse approaching 1 year. This direct comparison between the two subgroups of CBF AMLs delineates clear biological differences and corroborates the value of RQ-PCR.

Keywords: Core binding factor leukaemia, Minimal residual disease, Real time quantitative PCR, Leukemogenesis