title: Cartridge-based automated BCR-ABL1 mRNA quantification: solving the issues of standardization, at what cost?
abstract: BACKGROUND
  Molecular monitoring of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors is essential for therapeutic stratification. Inter-laboratory reproducibility is, therefore, a crucial issue which requires standardization and strict alignment of BCR-ABL1 values to the international scale. An automated cartridge-based assay (Xpert BCR-ABL Monitor(™), Cepheid) had been proposed as a robust alternative to non-automated assays. This study aimed to compare inter-laboratory reproducibility of automated and non-automated quantification, the possibility of converting automated results to the international scale, and the potential economic impact of automation.
  
  
  METHODS
  One hundred and eighteen blood samples from chronic myeloid leukemia patients treated with tyrosine kinase inhibitors were prospectively analyzed in two laboratories using both automated and non-automated assays. The economic evaluation involved a micro-costing study and average costs were assessed as a function of sample throughput.
  
  
  RESULTS
  Automated assays achieved similar inter-laboratory reproducibility to highly standardized non-automated assays and a short delay (≤6 h) between sampling and blood lysis had a positive impact on inter-laboratory reproducibility. Reporting automated BCR-ABL1 ratios on the international scale was possible using a specific conversion factor which may vary with batches. Cost assessment showed that automated assays could be relevant for annual activity levels below 300 since average costs were lower than those of the non-automated assays.
  
  
  CONCLUSIONS
  The Xpert BCR-ABL Monitor(™) assay could be appropriately used in a near-patient setting for routine quantification of e13/e14-a2 transcripts, preferably in partnership with a regional reference laboratory. However, its prognostic impact relative to non-automated quantification remains to be tested prospectively within appropriate clinical trials.
authors.affiliation: Laboratoire Central d'Hématologie, Hôpital Saint-Louis, 1 av. Claude Vellefaux, 75475 Paris cedex 10, France. jean-michel.cayuela@sls.aphp.fr
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Cayuela
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Macintyre
authors.forename: Meryl
authors.initials: M
authors.lastname: Darlington
authors.forename: Raouf Ben
authors.initials: RB
authors.lastname: Abdelali
authors.forename: Xavier
authors.initials: X
authors.lastname: Fund
authors.forename: Patrick
authors.initials: P
authors.lastname: Villarese
authors.forename: Michel
authors.initials: M
authors.lastname: Tulliez
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Raffoux
authors.forename: François
authors.initials: F
authors.lastname: Sigaux
authors.forename: Delphine
authors.initials: D
authors.lastname: Réa
authors.forename: Valerie
authors.initials: V
authors.lastname: Seror
mesh_terms: D019411:Clinical Laboratory Techniques / Q000191:economics / Q000379:methods / Q000592:standards*; D003365:Costs and Cost Analysis; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012015:Reference Standards; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
chemical_list: D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl