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Blood. 2013 Mar 21;121(12):2213-23. doi: 10.1182/blood-2012-10-462879. Epub 2013 Jan 15.

Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia.

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1
Department of Hematology and Oncology, Centre Hospitalier Universitaire (CHU) de Nimes, University Montpellier-Nimes, Nimes, France.

Abstract

Not all patients with core binding factor acute myeloid leukemia (CBF-AML) display a good outcome. Modern risk factors include KIT and/or FLT3 gene mutations and minimal residual disease (MRD) levels, but their respective values have never been prospectively assessed. A total of 198 CBF-AML patients were randomized between a reinforced and a standard induction course, followed by 3 high-dose cytarabine consolidation courses. MRD levels were monitored prospectively. Gene mutations were screened at diagnosis. Despite a more rapid MRD decrease after reinforced induction, induction arm did not influence relapse-free survival (RFS) (64% in both arms; P = .91). Higher WBC, KIT, and/or FLT3-ITD/TKD gene mutations, and a less than 3-log MRD reduction after first consolidation, were associated with a higher specific hazard of relapse, but MRD remained the sole prognostic factor in multivariate analysis. At 36 months, cumulative incidence of relapse and RFS were 22% vs 54% (P < .001) and 73% vs 44% (P < .001) in patients who achieved 3-log MRD reduction vs the others. These results suggest that MRD, rather than gene mutations, should be used for future treatment stratifications in CBF-AML patients. This trial was registered at EudraCT as #2006-005163-26 and at www.clinicaltrials.gov as #NCT 00428558.

PMID:
23321257
DOI:
10.1182/blood-2012-10-462879
[Indexed for MEDLINE]

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