title: Residual disease detected by flow cytometry is an independent predictor of survival in childhood acute myeloid leukaemia; results of the NOPHO-AML 2004 study.
abstract: Early response after induction is a prognostic factor for disease outcome in childhood acute myeloid leukaemia (AML). Residual disease (RD) detection by multiparameter flow cytometry (MFC) was performed at day 15 and before consolidation therapy in 101 patients enrolled in the Nordic Society of Paediatric Haemato-Oncology AML 2004 study. A multicentre laboratory approach to RD analysis was used. Event-free survival (EFS) and overall survival (OS) was significantly different in patients with and without RD at both time points, using a 0·1% RD cut-off level. RD-negative and -positive patients after first induction showed a 5-year EFS of 65 ± 7% and 22 ± 7%, respectively (P < 0·001) and an OS of 77 ± 6% (P = 0·025) and 51 ± 8%. RD-negative and -positive patients at start of consolidation therapy had a 5-year EFS of 57 ± 7% and 11 ± 7%, respectively (P < 0·001) and an OS of 78 ± 6% and 28 ± 11%) (P < 0·001). In multivariate analysis only RD was significantly correlated with survival. RD before consolidation therapy was the strongest independent prognostic factor for EFS [hazard ratio (HR):5·0; 95% confidence interval (CI):1·9-13·3] and OS (HR:7·0; 95%CI:2·0-24·5). In conclusion, RD before consolidation therapy identifies patients at high risk of relapse in need of intensified treatment. In addition, RD detection can be performed in a multicentre setting and can be implemented in future trials.
authors.affiliation: Department of Pathobiology and Laboratory Medicine, University Health Network, Toronto General Hospital, Toronto, ON, Canada.|Department of Pathology, Oslo University Hospital, Oslo, Norway.
authors.forename: Anne
authors.initials: A
authors.lastname: Tierens
authors.affiliation: Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bjørklund
authors.affiliation: Laboratory Services (Hospital District of Helsinki and Uusimaa Laboratory), Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Siitonen
authors.affiliation: Department of Clinical Immunology section 7631, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Hanne Vibeke
authors.initials: HV
authors.lastname: Marquart
authors.affiliation: Department of Clinical Immunology section 7631, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Gitte
authors.initials: G
authors.lastname: Wulff-Juergensen
authors.affiliation: Fimlab, Laboratories Ltd, Tampere, Finland.
authors.forename: Tarja-Terttu
authors.initials: TT
authors.lastname: Pelliniemi
authors.affiliation: University of Umeå, Umeå, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Forestier
authors.affiliation: Aarhus University, Hospital Skejby, Aarhus, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Hasle
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Jahnukainen
authors.affiliation: University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Lausen
authors.affiliation: Landspitali-University Hospital, Reykjavik, Iceland.
authors.forename: Olafur G
authors.initials: OG
authors.lastname: Jonsson
authors.affiliation: University Children's Hospital, Uppsala, Sweden.
authors.forename: Josefine
authors.initials: J
authors.lastname: Palle
authors.affiliation: Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Bem
authors.initials: B
authors.lastname: Zeller
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.|Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Fogelstrand
authors.affiliation: Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Abrahamsson
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000401:mortality*; D008297:Male; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000401:mortality; D011379:Prognosis; D012074:Remission Induction; D012306:Risk; D016019:Survival Analysis; D013997:Time Factors
keywords: acute myeloid leukaemia; flow cytometry; minimal residual disease; prognosis; survival