title: Comparison of molecular responses based on BCR-ABL1% (IS) results from an in-house TaqMan-based qPCR versus Xpert(®) assay in CML patients on tyrosine kinase inhibitor therapy.
abstract: OBJECTIVE
  Tyrosine kinase inhibitors (TKIs) have drastically changed the prospects for chronic myeloid leukemia (CML) patients. The European LeukemiaNet (ELN) recommends molecular monitoring of BCR-ABL1 mRNA levels at distinct time points to define an optimal response, warning, or failure of treatment.
  
  
  METHODS
  Sixty-four follow-up peripheral blood samples from CML patients on TKI were tested by two methods. Molecular responses based on BCR-ABL1% (IS) from an Xpert(®) BCR-ABL1 Monitor assay were compared with TaqMan-based qPCR.
  
  
  RESULTS
  Seven samples showed 'molecularly undetectable leukaemia' by both methods (11%). In-house qPCR showed 57 BCR-ABL1+ samples; 45/57 samples (79%) were concordant for 'major molecular response' (MMR, n = 32) and 'no MMR' (n = 13) by both assays, whereas nine were BCR-ABL1 negative by Xpert(®). Identical molecular responses (i.e. 'optimal') were defined in 41 samples. Discordances seen in patients < 10 months on TKI (n = 2) had no impact on clinical management, whereas for patients >12 months on TKI, a different molecular response was defined ('warning' versus 'optimal'). Thirteen samples had 'no MMR' by both methods. 10/13 showed identical intervals (>10%(IS), 1-10%(IS) or 0·1-1%(IS)), corresponding to seven 'failures' and three 'warnings'. Discordant intervals were seen in 3/13 samples (all defined as 'failures'). Deep molecular responses (MR(4·0) or MR(5·0)) with detectable BCR-ABL1 showed some fluctuations between both methods, nevertheless, all had 'optimal' responses. 'Molecularly undetectable leukaemia' was observed more frequently by Xpert(®) (n = 16) as by our in-house assay (n = 7).
  
  
  CONCLUSIONS
  Based on current ELN recommendations, Xpert(®) BCR-ABL1 assay defines identical molecular responses as TaqMan-based qPCR BCR-ABL1% (IS) data in 98% (63/64) of samples.
authors.forename: N
authors.initials: N
authors.lastname: Boeckx
authors.forename: C Van
authors.initials: CV
authors.lastname: Laer
authors.forename: J De
authors.initials: JD
authors.lastname: Roover
authors.forename: B
authors.initials: B
authors.lastname: Wilmsen
authors.forename: K
authors.initials: K
authors.lastname: Bruyninckx
authors.forename: S
authors.initials: S
authors.lastname: Pauwels
mesh_terms: D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D058990:Molecular Targeted Therapy; D016133:Polymerase Chain Reaction; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000097:blood
chemical_list: C581634:BCR-ABL1 fusion protein, human; D047428:Protein Kinase Inhibitors; D012334:RNA, Neoplasm; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl
keywords: BCR-ABL1 ,; CML,; PCR,; Tyrosine kinase inhibitor; Xpert® BCR-ABL monitor,