Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia
Eric Jourdan, Nicolas Boissel, Sylvie Chevret, Eric Delabesse, Aline Renneville, Pascale Cornillet, Odile Blanchet, Jean-Michel Cayuela, Christian Recher, Emmanuel Raffoux, Jacques Delaunay, Arnaud Pigneux, Claude-Eric Bulabois, Céline Berthon, Cécile Pautas, Norbert Vey, Bruno Lioure, Xavier Thomas, Isabelle Luquet, Christine Terré, Philippe Guardiola, Marie C Béné, Claude Preudhomme, Norbert Ifrah, Hervé Dombret, French AML Intergroup, Eric Jourdan, Nicolas Boissel, Sylvie Chevret, Eric Delabesse, Aline Renneville, Pascale Cornillet, Odile Blanchet, Jean-Michel Cayuela, Christian Recher, Emmanuel Raffoux, Jacques Delaunay, Arnaud Pigneux, Claude-Eric Bulabois, Céline Berthon, Cécile Pautas, Norbert Vey, Bruno Lioure, Xavier Thomas, Isabelle Luquet, Christine Terré, Philippe Guardiola, Marie C Béné, Claude Preudhomme, Norbert Ifrah, Hervé Dombret, French AML Intergroup
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.
Trial registration: ClinicalTrials.gov NCT00428558.
Source: PubMed