title: Cepheid xpert monitor platform for the confirmation of BCR-ABL1 IS conversion factors for the molecular monitoring of chronic myeloid leukaemia.
abstract: Molecular monitoring of BCR-ABL1 expression in chronic myeloid leukaemia (CML) is well established. As the International Scale (IS) normalised BCR-ABL1/ABL1 ratio at 3 months post-treatment is now an important milestone in patients' treatment schedule, the reliable and reproducible measurement of BCR-ABL1 levels is therefore paramount. IS conversion factors (CF) are established via sample exchange and yearly ratification with an external reference laboratory. Since any change to an established IS CF could lead to discontinuity in longitudinal results, we wished to add an internal verification step as an additional safeguard. We used the Cepheid GeneXpert qPCR and IS calibrated Xpert BCR-ABL Monitor cartridge system, parallel to our in-house pipeline on 50 CML samples, over the period of one week to verify the CF for those samples and compare it to the externally provided CF. The median non-IS in-house BCR-ABL1/ABL1 values were significantly different than that from the IS GeneXpert, but they became non-significant when adjusted to CF provided by the CXM and by the current external CF, validating it. These metrics can help decide to accept or reject an updated CF value, especially where a significant change in CF might lead to a discontinuity in ongoing patient monitoring.
authors.affiliation: Centre for Haematology, Imperial College London, Du Cane Road, London W12 ONN, UK; Research Department of Pathology, UCL Cancer Institute, London WC1E 6DE, UK. Electronic address: g.gerrard@ucl.ac.uk.
authors.forename: Gareth
authors.initials: G
authors.lastname: Gerrard
authors.affiliation: Centre for Haematology, Imperial College London, Du Cane Road, London W12 ONN, UK; Imperial Molecular Pathology, Imperial Healthcare NHS Trust, Hammersmith Hospital, Du Cane Road, London W12 OHS, UK.
authors.forename: Hui En
authors.initials: HE
authors.lastname: Foong
authors.affiliation: Imperial Molecular Pathology, Imperial Healthcare NHS Trust, Hammersmith Hospital, Du Cane Road, London W12 OHS, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Mudge
authors.affiliation: Centre for Haematology, Imperial College London, Du Cane Road, London W12 ONN, UK.
authors.forename: Mary
authors.initials: M
authors.lastname: Alikian
authors.affiliation: Centre for Haematology, Imperial College London, Du Cane Road, London W12 ONN, UK; Imperial Molecular Pathology, Imperial Healthcare NHS Trust, Hammersmith Hospital, Du Cane Road, London W12 OHS, UK.
authors.forename: Jane F
authors.initials: JF
authors.lastname: Apperley
authors.affiliation: Centre for Haematology, Imperial College London, Du Cane Road, London W12 ONN, UK; Imperial Molecular Pathology, Imperial Healthcare NHS Trust, Hammersmith Hospital, Du Cane Road, London W12 OHS, UK.
authors.forename: Letizia
authors.initials: L
authors.lastname: Foroni
mesh_terms: D016044:Fusion Proteins, bcr-abl / Q000032:analysis*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis*; D008991:Monitoring, Physiologic / Q000379:methods* / Q000592:standards; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012015:Reference Standards
chemical_list: D016044:Fusion Proteins, bcr-abl
keywords: BCR-ABL1; Chronic myeloid leukaemia; Standardisation; molecular monitoring