Minimal residual disease detection in childhood acute lymphoblastic leukaemia patients at multiple time-points reveals high levels of concordance between molecular and immunophenotypic approaches

Jacqueline Ryan, Fiona Quinn, Armelle Meunier, Ludmila Boublikova, Mireille Crampe, Prerna Tewari, Aengus O'Marcaigh, Ray Stallings, Michael Neat, Ann O'Meara, Fin Breatnach, Shaun McCann, Paul Browne, Owen Smith, Mark Lawler, Mark Lawler

Research output: Contribution to journalArticle

38 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)107-15
Number of pages9
JournalBritish Journal of Haematology
Volume144
Issue number1
DOIs
Publication statusPublished - Jan 2009

Keywords

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols
  • Bone Marrow Examination
  • Child
  • Child, Preschool
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Humans
  • Immunophenotyping
  • Infant
  • Kaplan-Meier Estimate
  • Male
  • Neoplasm, Residual
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Prospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity

Fingerprint Dive into the research topics of 'Minimal residual disease detection in childhood acute lymphoblastic leukaemia patients at multiple time-points reveals high levels of concordance between molecular and immunophenotypic approaches'. Together they form a unique fingerprint.

Cite this