title: A BCR-ABL1 cutoff of 1.5% at 3 months, determined by the GeneXpert system, predicts an optimal response in patients with chronic myeloid leukemia.
abstract: In chronic myeloid leukemia (CML) patients, 3-month BCR-ABL1 levels have consistently been correlated with further outcomes. Monitoring molecular responses in CML using the GeneXpert (Cepheid) platform has shown an optimal correlation with standardized RQ-PCR (IS) when measuring BCR-ABL1 levels lower than 10%, as it is not accurate for values over 10%. The aim of the present study was to determine the predictive molecular value at three months on different outcome variables using the Xpert BCR-ABL1 MonitorTM assay (Xpert BCR-ABL1). We monitored 125 newly diagnosed consecutive CML patients in the chronic phase (CML-CP) using an automated method: Xpert BCR-ABL1. Only 5% of patients did not achieve an optimal response at 3 months, and the 10% BCR-ABL1 cutoff defined by RQ-PCR (IS) methods was unable to identify significant differences in the probabilities of achieving a complete cytogenetic response (CCyR) (50% vs. 87%, p = 0.1) or a major molecular response (MMR) (60% vs. 80%, p = 0.29) by 12 months. In contrast, a cutoff of 1.5% more accurately identified differences in the probabilities of achieving CCyR (98% vs. 54%, p<0.001) and MMR (88% vs. 56%, p<0.001) by 12 months, as well as probabilities of treatment changes (p = 0.005). Therefore, when using the Xpert BCR-ABL1 assay, a cutoff of 1.5% at 3 months could with high probability identify patients able to achieve an optimal response at 12 months.
authors.affiliation: Hematology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: Valentín
authors.initials: V
authors.lastname: García-Gutiérrez
authors.affiliation: Hematology Department, Hospital Universitario Doctor Negrín, Las Palmas de Gran Canaria, Spain.
authors.forename: María T
authors.initials: MT
authors.lastname: Gómez-Casares
authors.affiliation: Unidad de Gestión Clínica Hematología y Hemoterapia, Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Puerta
authors.affiliation: Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Alonso-Domínguez
authors.affiliation: Hematology Department, Hospital Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Osorio
authors.affiliation: Hematology Department, Hospital Clínico, Valencia, Spain.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Hernández-Boluda
authors.affiliation: Genetic Laboratory, Hematology Department, Consorcio Hospital General Universitario, Valencia, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Collado
authors.affiliation: Hematology Department, Hospital de Jerez de la Frontera, Cádiz, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Ramírez
authors.affiliation: Hematology Department, Hospital San Pedro de Alcántara, Cáceres, Spain.
authors.forename: Fátima
authors.initials: F
authors.lastname: Ibáñez
authors.affiliation: Hematology Department, Hospital Universitario Virgen Macarena, Sevilla, Spain.
authors.forename: María L
authors.initials: ML
authors.lastname: Martín
authors.affiliation: Hematology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: Juan D
authors.initials: JD
authors.lastname: Rodríguez-Gambarte
authors.affiliation: Hematology Department, Hospital Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Martínez-Laperche
authors.affiliation: Hematology Department, Hospital Clínico, Valencia, Spain.
authors.forename: Montse
authors.initials: M
authors.lastname: Gómez
authors.affiliation: Hematology Department, Hospital Universitario Doctor Negrín, Las Palmas de Gran Canaria, Spain.
authors.forename: Dolly V
authors.initials: DV
authors.lastname: Fiallo
authors.affiliation: Hematology Department, Hospital Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Redondo
authors.affiliation: Hematology Department, Hospital Universitario Virgen Macarena, Sevilla, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Rodríguez
authors.affiliation: Hematology Department, Hospital Regional Universitario de Málaga, IBIMA, Málaga, Spain.
authors.forename: Concepción
authors.initials: C
authors.lastname: Ruiz-Nuño
authors.affiliation: Hematology Department & IIS-IP, Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Juan L
authors.initials: JL
authors.lastname: Steegmann
authors.affiliation: Hematology Department, Hospital Regional Universitario de Málaga, IBIMA, Málaga, Spain.
authors.forename: Antonio
authors.identifier: http://orcid.org/0000-0001-6421-7872
authors.initials: A
authors.lastname: Jiménez-Velasco
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction / Q000379:methods*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
chemical_list: D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl