title: Early assessment of minimal residual disease in AML by flow cytometry during aplasia identifies patients at increased risk of relapse.
abstract: In acute myeloid leukemia (AML), assessment of minimal residual disease (MRD) by flow cytometry (flow MRD) after induction and consolidation therapy has been shown to provide independent prognostic information. However, data on the value of earlier flow MRD assessment are lacking. Therefore, the value of flow MRD detection was determined during aplasia in 178 patients achieving complete remission after treatment according to AMLCG (AML Cooperative Group) induction protocols. Flow MRD positivity during aplasia predicted poor outcome (5-year relapse-free survival (RFS) 16% vs 43%, P<0.001) independently from age and cytogenetic risk group (hazard ratio for MRD positivity 1.71; P=0.009). Importantly, the prognosis of patients without detectable MRD was neither impacted by morphological blast count during aplasia nor by MRD status postinduction. Early flow MRD was also evaluated in the context of existing risk factors. Flow MRD was prognostic within the intermediate cytogenetic risk group (5-year RFS 15% vs 37%, P=0.016) as well as for patients with normal karyotype and NPM1 mutations (5-year RFS 13% vs 49%, P=0.02) or FLT3-ITD (3-year RFS rates 9% vs 44%, P=0.016). Early flow MRD assessment can improve current risk stratification approaches by prediction of RFS in AML and might facilitate adaptation of postremission therapy for patients at high risk of relapse.
authors.affiliation: Department of Internal Medicine III, University of Munich, Munich, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Köhnke
authors.affiliation: Department of Internal Medicine III, University of Munich, Munich, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Sauter
authors.affiliation: Department of Internal Medicine III, University of Munich, Munich, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Ringel
authors.affiliation: 1] Department of Internal Medicine III, University of Munich, Munich, Germany [2] Institute of Medical Informatics, Biometry and Epidemiology (IBE), University of Munich, Munich, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Hoster
authors.affiliation: Institute of Medical Informatics, Biometry and Epidemiology (IBE), University of Munich, Munich, Germany.
authors.forename: R P
authors.initials: RP
authors.lastname: Laubender
authors.affiliation: Department of Internal Medicine III, University of Munich, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hubmann
authors.affiliation: 1] Department of Internal Medicine III, University of Munich, Munich, Germany [2] Department of Human Genetics, Philipps University Marburg, Marburg, Germany.
authors.forename: S K
authors.initials: SK
authors.lastname: Bohlander
authors.affiliation: Department of Human Genetics, Philipps University Marburg, Marburg, Germany.
authors.forename: P M
authors.initials: PM
authors.lastname: Kakadia
authors.affiliation: Department of Internal Medicine III, University of Munich, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schneider
authors.affiliation: Department of Internal Medicine III, University of Munich, Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Dufour
authors.affiliation: Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany.
authors.forename: M-C
authors.initials: MC
authors.lastname: Sauerland
authors.affiliation: Department of Internal Medicine IIIA, University of Münster, Münster, Germany.
authors.forename: W E
authors.initials: WE
authors.lastname: Berdel
authors.affiliation: Department of Internal Medicine IIIA, University of Münster, Münster, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Büchner
authors.affiliation: German Society of Hematology and Oncology (DGHO), Berlin, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Wörmann
authors.affiliation: Department of Hematology and Oncology, Barmherzige Brüder Hospital, Regensburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Braess
authors.affiliation: 1] Department of Internal Medicine III, University of Munich, Munich, Germany [2] Clinical Cooperation Group Acute Myeloid Leukemia, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Munich, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Hiddemann
authors.affiliation: 1] Department of Internal Medicine III, University of Munich, Munich, Germany [2] Clinical Cooperation Group Acute Myeloid Leukemia, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Munich, Germany [3] German Cancer Consortium (DKTK), Heidelberg, Germany [4] German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Spiekermann
authors.affiliation: 1] Department of Internal Medicine III, University of Munich, Munich, Germany [2] Clinical Cooperation Group Immunotherapy, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Subklewe
mesh_terms: D000368:Aged; D001853:Bone Marrow / Q000002:abnormalities*; D001854:Bone Marrow Cells / Q000166:cytology*; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood*; D018365:Neoplasm, Residual / Q000175:diagnosis*; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D011379:Prognosis; D016016:Proportional Hazards Models; D012074:Remission Induction; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin