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Minimal residual disease monitoring by quantitative RT-PCR in core binding factor AML allows risk stratification and predicts relapse: results of the United Kingdom MRC AML-15 trial

Yin, John A. Liu, O'Brien, Michelle A., Hills, Robert Kerrin, Daly, Sarah B., Wheatley, Keith and Burnett, Alan Kenneth 2012. Minimal residual disease monitoring by quantitative RT-PCR in core binding factor AML allows risk stratification and predicts relapse: results of the United Kingdom MRC AML-15 trial. Blood 120 (14) , pp. 2826-2835. 10.1182/blood-2012-06-435669

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Abstract

The clinical value of serial minimal residual disease (MRD) monitoring in core binding factor (CBF) acute myeloid leukemia (AML) by quantitative RT-PCR was prospectively assessed in 278 patients [163 with t(8;21) and 115 with inv(16)] entered in the United Kingdom MRC AML 15 trial. CBF transcripts were normalized to 105 ABL copies. At remission, after course 1 induction chemotherapy, a > 3 log reduction in RUNX1-RUNX1T1 transcripts in BM in t(8;21) patients and a > 10 CBFBMYH11 copy number in peripheral blood (PB) in inv(16) patients were the most useful prognostic variables for relapse risk on multivariate analysis. MRD levels after consolidation (course 3) were also informative. During follow-up, cut-off MRD thresholds in BM and PB associated with a 100% relapse rate were identified: for t(8;21) patients BM > 500 copies, PB > 100 copies; for inv(16) patients, BM > 50 copies and PB > 10 copies. Rising MRD levels on serial monitoring accurately predicted hematologic relapse. During follow-up, PB sampling was equally informative as BM for MRD detection. We conclude that MRD monitoring by quantitative RT-PCR at specific time points in CBF AML allows identification of patients at high risk of relapse and could now be incorporated in clinical trials to evaluate the role of risk directed/preemptive therapy.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher: American Society of Hematology
ISSN: 0006-4971
Last Modified: 25 Jun 2017 04:20
URI: http://orca-mwe.cf.ac.uk/id/eprint/49798

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