title: MRD assessed by WT1 and NPM1 transcript levels identifies distinct outcomes in AML patients and is influenced by gemtuzumab ozogamicin.
abstract: We analysed the prognostic significance of minimal residual disease (MRD) level in adult patients with acute myeloid leukemia (AML) treated in the randomized gemtuzumab ozogamicin (GO) ALFA-0701 trial. Levels of WT1 and NPM1 gene transcripts were assessed using cDNA-based real-time quantitative PCR in 183 patients with WT1 overexpression and in 77 patients with NMP1 mutation (NPM1mut) at diagnosis. Positive WT1 MRD (defined as > 0.5% in the peripheral blood) after induction and at the end of treatment were both significantly associated with a higher risk of relapse and a shorter overall survival (OS). Positive NPM1mut MRD (defined as > 0.1% in the bone marrow) after induction and at the end of treatment also predicted a higher risk of relapse, but did not influence OS. Interestingly, the achievement of a negative NPM1mut MRD was significantly more frequent in patients treated in the GO arm compared to those treated in control arm (39 % versus 7% (p=0.006) after induction and 91% versus 61% (p=0.028) at the end of treatment). However, GO did not influence WT1 MRD levels. Our study supports the prognostic significance of MRD assessed by WT1 and NPM1mut transcript levels and show that NPM1 MRD is decreased by GO treatment.
authors.affiliation: Department of Hematology, Hôpital de Versailles, Le Chesnay, Université de Versailles-Saint Quentin; France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Lambert
authors.affiliation: INSERM UMR-S 717, Paris; France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Lambert
authors.affiliation: Laboratory of Hematology, CHRU de Lille; Université de Lille Nord de France, Inserm, U837, Team 3, Cancer Research Institute of Lille, Lille; France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Nibourel
authors.affiliation: Department of Hematology, Hôpital Henri Mondor, AP-HP, Créteil; France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Pautas
authors.affiliation: Laboratory of Hematology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, UMR5239, Université Claude Bernard, Lyon; France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Hayette
authors.affiliation: Laboratory of Hematology, Hôpital Saint-Louis, AP-HP, EA3518, University Paris Diderot, Paris; France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Cayuela
authors.affiliation: Laboratory of Cytogenetics, Hôpital de Versailles, Le Chesnay; France.
authors.forename: Christine
authors.initials: C
authors.lastname: Terré
authors.affiliation: Department of Hematology, Hôpital de Versailles, Le Chesnay, Université de Versailles-Saint Quentin; France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rousselot
authors.affiliation: Department of Hematology, Hôpital Saint Louis, AP-HP, Université Paris Diderot, EA 3518, Paris; France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Dombret
authors.affiliation: Department of Informatics and Biostatistics, Hôpital Saint Louis, Université Paris Diderot, INSERM S 717, Paris; France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
authors.affiliation: Laboratory of Hematology, CHRU de Lille; Université de Lille Nord de France, Inserm, U837, Team 3, Cancer Research Institute of Lille, Lille; France.
authors.forename: Claude
authors.initials: C
authors.lastname: Preudhomme
authors.affiliation: Department of Hematology, Hôpital de Versailles, Le Chesnay, Université de Versailles-Saint Quentin; France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Castaigne
authors.affiliation: Laboratory of Hematology, CHRU de Lille; Université de Lille Nord de France, Inserm, U837, Team 3, Cancer Research Institute of Lille, Lille; France.
authors.forename: Aline
authors.initials: A
authors.lastname: Renneville
mesh_terms: D000368:Aged; D000617:Aminoglycosides / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005260:Female; D000079982:Gemtuzumab; D016162:Genes, Wilms Tumor; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D025721:WT1 Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000617:Aminoglycosides; D061067:Antibodies, Monoclonal, Humanized; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D025721:WT1 Proteins; C583751:WT1 protein, human; D003561:Cytarabine; D000090243:Nucleophosmin; D000079982:Gemtuzumab; D003630:Daunorubicin