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

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...

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Published in:Blood 2013-03, Vol.121 (12), p.2213-2223
Main Authors: Jourdan, Eric, Boissel, Nicolas, Chevret, Sylvie, Delabesse, Eric, Renneville, Aline, Cornillet, Pascale, Blanchet, Odile, Cayuela, Jean-Michel, Recher, Christian, Raffoux, Emmanuel, Delaunay, Jacques, Pigneux, Arnaud, Bulabois, Claude-Eric, Berthon, Céline, Pautas, Cécile, Vey, Norbert, Lioure, Bruno, Thomas, Xavier, Luquet, Isabelle, Terré, Christine, Guardiola, Philippe, Béné, Marie C., Preudhomme, Claude, Ifrah, Norbert, Dombret, Hervé
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Language:English
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Summary: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. •In adult patients with core binding factor AML, intensified induction is not associated with a better outcome in the context of intensive postremission therapy.•Minimal residual disease, rather than KIT or FLT3 gene mutations, should be used to identify core binding factor AML patients at higher risk of relapse.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2012-10-462879