title: 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: Department of Hematology and Oncology, Centre Hospitalier Universitaire (CHU) de Nimes, University Montpellier-Nimes, Nimes, France.
authors: Eric
authors: E
authors: Jourdan
authors: Nicolas
authors: N
authors: Boissel
authors: Sylvie
authors: S
authors: Chevret
authors: Eric
authors: E
authors: Delabesse
authors: Aline
authors: A
authors: Renneville
authors: Pascale
authors: P
authors: Cornillet
authors: Odile
authors: O
authors: Blanchet
authors: Jean-Michel
authors: JM
authors: Cayuela
authors: Christian
authors: C
authors: Recher
authors: Emmanuel
authors: E
authors: Raffoux
authors: Jacques
authors: J
authors: Delaunay
authors: Arnaud
authors: A
authors: Pigneux
authors: Claude-Eric
authors: CE
authors: Bulabois
authors: Céline
authors: C
authors: Berthon
authors: Cécile
authors: C
authors: Pautas
authors: Norbert
authors: N
authors: Vey
authors: Bruno
authors: B
authors: Lioure
authors: Xavier
authors: X
authors: Thomas
authors: Isabelle
authors: I
authors: Luquet
authors: Christine
authors: C
authors: Terré
authors: Philippe
authors: P
authors: Guardiola
authors: Marie C
authors: MC
authors: Béné
authors: Claude
authors: C
authors: Preudhomme
authors: Norbert
authors: N
authors: Ifrah
authors: Hervé
authors: H
authors: Dombret
mesh_terms: D000293:Adolescent; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D050660:Core Binding Factors / Q000235:genetics*; D003561:Cytarabine / Q000008:administration & dosage; D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D018365:Neoplasm, Residual; D011379:Prognosis; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D050660:Core Binding Factors; D003561:Cytarabine