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

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.

• Authors: 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
• Journal: Blood (Blood) Vol. 121 Issue 12 Pg. 2213-23 (Mar 21 2013) ISSN: 1528-0020 [Electronic] United States
• PMID: 23321257 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Core Binding Factors
• Cytarabine

Topics

• Adolescent
• Adult
• Antimetabolites, Antineoplastic (administration & dosage)
• Core Binding Factors (genetics)
• Cytarabine (administration & dosage)
• DNA Mutational Analysis
• Drug Resistance, Neoplasm (genetics)
• Female
• Genes, Neoplasm (genetics)
• Humans
• Leukemia, Myeloid, Acute (diagnosis, drug therapy, genetics, pathology)
• Male
• Middle Aged
• Mutation (physiology)
• Neoplasm, Residual
• Prognosis
• Prospective Studies
• Treatment Outcome
• Young Adult