title: Prospective long-term minimal residual disease monitoring using RQ-PCR in RUNX1-RUNX1T1-positive acute myeloid leukemia: results of the French CBF-2006 trial.
abstract: In t(8;21)(q22;q22) acute myeloid leukemia, the prognostic value of early minimal residual disease assessed with real-time quantitative polymerase chain reaction is the most important prognostic factor, but how long-term minimal residual disease monitoring may contribute to drive individual patient decisions remains poorly investigated. In the multicenter CBF-2006 study, a prospective monitoring of peripheral blood and bone marrow samples was performed every 3 months and every year, respectively, for 2 years following intensive chemotherapy in 94 patients in first complete remission. A complete molecular remission was defined as a (RUNX1-RUNX1T1/ABL1)×100 ≤ 0.001%. After the completion of consolidation therapy, a bone marrow complete molecular remission was observed in 30% of the patients, but was not predictive of subsequent relapse. Indeed, 8 patients (9%) presented a positive bone marrow minimal residual disease for up to 2 years of follow-up while still remaining in complete remission. Conversely, a peripheral blood complete molecular remission was statistically associated with a lower risk of relapse whatever the time-point considered after the completion of consolidation therapy. During the 2-year follow-up, the persistence of peripheral blood complete molecular remission was associated with a lower risk of relapse (4-year cumulative incidence, 8.2%), while molecular relapse confirmed on a subsequent peripheral blood sample predicted hematological relapse (4-year cumulative incidence, 86.9%) within a median time interval of 3.9 months. In t(8;21)(q22;q22) acute myeloid leukemia, minimal residual disease monitoring on peripheral blood every 3 months allows for the prediction of hematological relapse, and to identify patients who could potentially benefit from intervention therapy. (ClinicalTrials.gov ID #NCT00428558).
authors.affiliation: Maladie du Sang, Hôpital Claude Huriez, Lille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Willekens
authors.affiliation: Département Hématologie-Immunologie CHU Angers, Tumor Bank CHU-ICO, CRB-CHU Angers, BB-0033-00038, UMR Inserm 892 CNRS 6299 CRCNA, Université d'Anger, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Blanchet
authors.affiliation: Laboratoire d'hématologie, Centre de Biologie-Pathologie, CHRU de Lille; Equipe 3 INSERM U837, JPARC Lille, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Renneville
authors.affiliation: Laboratoire d'Hématologie, Centre Hospitalier Universitaire de Reims, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Cornillet-Lefebvre
authors.affiliation: Hématologie Clinique, Centre Hospitalier Henri Mondor, Créteil, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Pautas
authors.affiliation: Hématologie Clinique, Centre Hospitalier Universitaire, Clermont-Ferrand, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Guieze
authors.affiliation: Hématologie Clinique, Centre Hospitalier Universitaire, Angers, France.
authors.forename: Norbert
authors.initials: N
authors.lastname: Ifrah
authors.affiliation: Département d'Hématologie, Hôpital Saint-Louis, EA3518, Institut Universitaire d'Hématologie, Université Paris 7, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Dombret
authors.affiliation: Service d'Hématologie, Centre Hospitalier Universitaire de Nîmes, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Jourdan
authors.affiliation: Laboratoire d'hématologie, Centre de Biologie-Pathologie, CHRU de Lille; Equipe 3 INSERM U837, JPARC Lille, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Preudhomme
authors.forename: Nicolas
authors.initials: N
authors.lastname: Boissel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001773:Blood Cells / Q000378:metabolism / Q000473:pathology; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002892:Chromosomes, Human, Pair 22; D002898:Chromosomes, Human, Pair 8; D060830:Consolidation Chemotherapy / Q000379:methods; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005602:France; D015870:Gene Expression; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D018365:Neoplasm, Residual; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D000075142:RUNX1 Translocation Partner 1 Protein; D060888:Real-Time Polymerase Chain Reaction; D012008:Recurrence; D012074:Remission Induction; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic
chemical_list: C513733:ABI1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D050676:Core Binding Factor Alpha 2 Subunit; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; C493728:RUNX1 protein, human; C082222:RUNX1T1 protein, human; D014157:Transcription Factors