title: Minimal residual disease detection in childhood acute lymphoblastic leukaemia patients at multiple time-points reveals high levels of concordance between molecular and immunophenotypic approaches.
abstract: In this single centre study of childhood acute lymphoblastic leukaemia (ALL) patients treated on the Medical Research Council UKALL 97/99 protocols, it was determined that minimal residual disease (MRD) detected by real time quantitative polymerase chain reaction (RQ-PCR) and 3-colour flow cytometry (FC) displayed high levels of qualitative concordance when evaluated at multiple time-points during treatment (93.38%), and a combined use of both approaches allowed a multi time-point evaluation of MRD kinetics for 90% (53/59) of the initial cohort. At diagnosis, MRD markers with sensitivity of at least 0.01% were identified by RQ-PCR detection of fusion gene transcripts, IGH/TRG rearrangements, and FC. Using a combined RQ-PCR and FC approach, the evaluation of 367 follow-up BM samples revealed that the detection of MRD >1% at Day 15 (P = 0.04), >0.01% at the end of induction (P = 0.02), >0.01% at the end of consolidation (P = 0.01), >0.01% prior to the first delayed intensification (P = 0.01), and >0.1% prior to the second delayed intensification and continued maintenance (P = 0.001) were all associated with relapse and, based on early time-points (end of induction and consolidation) a significant log-rank trend (P = 0.0091) was noted between survival curves for patients stratified into high, intermediate and low-risk MRD groups.
authors.affiliation: The John Durkan Laboratory for Leukaemia Research, Institute of Molecular Medicine, St James's Hospital & Trinity College Dublin, University of Dublin, Dublin, Ireland. jmryan@tcd.ie
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Ryan
authors.forename: Fiona
authors.initials: F
authors.lastname: Quinn
authors.forename: Armelle
authors.initials: A
authors.lastname: Meunier
authors.forename: Ludmila
authors.initials: L
authors.lastname: Boublikova
authors.forename: Mireille
authors.initials: M
authors.lastname: Crampe
authors.forename: Prerna
authors.initials: P
authors.lastname: Tewari
authors.forename: Aengus
authors.initials: A
authors.lastname: O'Marcaigh
authors.forename: Ray
authors.initials: R
authors.lastname: Stallings
authors.forename: Michael
authors.initials: M
authors.lastname: Neat
authors.forename: Ann
authors.initials: A
authors.lastname: O'Meara
authors.forename: Fin
authors.initials: F
authors.lastname: Breatnach
authors.forename: Shaun
authors.initials: S
authors.lastname: McCann
authors.forename: Paul
authors.initials: P
authors.lastname: Browne
authors.forename: Owen
authors.initials: O
authors.lastname: Smith
authors.forename: Mark
authors.initials: M
authors.lastname: Lawler
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001856:Bone Marrow Examination / Q000379:methods; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D018365:Neoplasm, Residual / Q000175:diagnosis*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity