title: Minimal residual disease evaluation by flow cytometry is a complementary tool to cytogenetics for treatment decisions in acute myeloid leukaemia.
abstract: The clinical utility of minimal residual disease (MRD) analysis in acute myeloid leukaemia (AML) is not yet defined. We analysed the prognostic impact of MRD level at complete remision after induction therapy using multiparameter flow cytometry in 306 non-APL AML patients. First, we validated the prognostic value of MRD-thresholds we have previously proposed (≥ 0.1%; ≥ 0.01-0.1%; and <0.01), with a 5-year RFS of 38%, 50% and 71%, respectively (p=0.002). Cytogenetics is the most relevant prognosis factor in AML, however intermediate risk cytogenetics represent a grey zone that require other biomarkers for risk stratification, and we show that MRD evaluation discriminate three prognostic subgroups (p=0.03). Also, MRD assessments yielded relevant information on favourable and adverse cytogenetics, since patients with favourable cytogenetics and high MRD levels have poor prognosis and patients with adverse cytogenetics but undetectable MRD overcomes the adverse prognosis. Interestingly, in patients with intermediate or high MRD levels, intensification with transplant improved the outcome as compared with chemotherapy, while the type of intensification therapy did not influenced the outcome of patients with low MRD levels. Multivariate analysis revealed age, MRD and cytogenetics as independent variables. Moreover, a scoring system, easy in clinical practice, was generated based on MRD level and cytogenetics.
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Spain; Instituto de Biología Molecular y Celular del Cáncer (CIC-CSIC), Salamanca, Spain.
authors.forename: María-Belén
authors.initials: MB
authors.lastname: Vidriales
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Spain. Electronic address: estefipe83@hotmail.com.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Pérez-López
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Spain.
authors.forename: Carlota
authors.initials: C
authors.lastname: Pegenaute
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Castellanos
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Spain.
authors.forename: José-Juan
authors.initials: JJ
authors.lastname: Pérez
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Spain.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Chandía
authors.affiliation: Department of Hematology, Hospital Universitario de San Carlos, Madrid, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Díaz-Mediavilla
authors.affiliation: Department of Hematology, Hospital Central de Asturias, Oviedo, Spain.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Rayón
authors.affiliation: Department of Hematology, Complejo Hospitalario de León, León, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: de Las Heras
authors.affiliation: Department of Hematology, Hospital Universitario Alicante, Alicante, Spain.
authors.forename: Pascual
authors.initials: P
authors.lastname: Fernández-Abellán
authors.affiliation: Department of Hematology, Complejo Asistencial de Ávila, Ávila, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Cabezudo
authors.affiliation: Department of Hematology, Hospital Clínico Universitario, Valladolid, Spain.
authors.forename: Alfonso García
authors.initials: AG
authors.lastname: de Coca
authors.affiliation: Department of Hematology, Hospital Río Carrión, Palencia, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Alonso
authors.affiliation: Department of Hematology, Complejo Asistencial, Segovia, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Olivier
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Spain; Instituto de Biología Molecular y Celular del Cáncer (CIC-CSIC), Salamanca, Spain.
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Hernández-Rivas
authors.affiliation: Department of Hematology, Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Pau
authors.initials: P
authors.lastname: Montesinos
authors.affiliation: Department of Hematology, Hospital Materno Insular, Las Palmas de Gran Canaria, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Fernández
authors.affiliation: Department of Hematology, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: García-Suárez
authors.affiliation: Department of Hematology, Hospital Virgen de la Concha, Zamora, Spain.
authors.forename: Magdalena
authors.initials: M
authors.lastname: García
authors.affiliation: Department of Hematology, Hospital Universitario Dr. Peset, Valencia, Spain.
authors.forename: María-José
authors.initials: MJ
authors.lastname: Sayas
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Spain; Instituto de Biología Molecular y Celular del Cáncer (CIC-CSIC), Salamanca, Spain.
authors.forename: Bruno
authors.initials: B
authors.lastname: Paiva
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Spain; Instituto de Biología Molecular y Celular del Cáncer (CIC-CSIC), Salamanca, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: González
authors.affiliation: Instituto de Biología Molecular y Celular del Cáncer (CIC-CSIC), Salamanca, Spain; Department of Cytometry, Universidad de Salamanca, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Spain; Instituto de Biología Molecular y Celular del Cáncer (CIC-CSIC), Salamanca, Spain.
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D000368:Aged; D002869:Chromosome Aberrations; D005434:Flow Cytometry; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D018365:Neoplasm, Residual
keywords: Acute myeloid leukaemia; Flow cytometry; Minimal residual disease; Prognosis