title: The significance of peripheral blood minimal residual disease to predict early disease response in patients with B-cell acute lymphoblastic leukemia.
abstract: BACKGROUND
  Minimal residual disease (MRD) assessment in the bone marrow (BM) postinduction therapy is now standard of care in patients with B-cell acute lymphoblastic leukemia (B-ALL). We examined the use of peripheral blood as a less invasive means of MRD assessment at days 8 and 15 of induction therapy and established the cutoff level that would allow the most accurate prediction of BM MRD postinduction therapy.
  
  
  METHODS
  MRD analysis was performed using 5-color flow cytometry on BM and PB samples from 77 B-ALL patients. BM MRD at diagnosis and day 29 of induction therapy was analyzed using the following antibody combinations: CD45-PC5/CD19-PC7/CD20-PE/CD10-ECD/CD38-FITC/CD13 + CD33-PE/CD10-ECD/CD34-FITC. PB MRD at days 8 and 15 was determined using CD45-PC5/CD19-PC7/CD20-ECD/CD10-PE/CD34-FITC.
  
  
  RESULTS
  Day 8 and day 15 PB MRD levels were significantly higher in patients who had persistent BM MRD at day 29. PB MRD <0.01% at day 8 and/or day 15 predicted negative day 29 BM MRD status with 100% sensitivity but poor specificity. ROC curve analysis showed that day 15 PB MRD level of 0.1% yielded the highest sensitivity (78%) and specificity (82%).
  
  
  CONCLUSIONS
  PB MRD cutoff level of 0.1% at day 15 has the best predictive value in determining positive day 29 BM MRD.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Setiadi
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Owen
authors.affiliation: Division of Hematopathology, BC Children's Hospital, Vancouver, BC, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Tsang
authors.affiliation: Child & Family Research Institute, Vancouver, BC, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Milner
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada. SVercauteren2@cw.bc.ca.|Division of Hematopathology, BC Children's Hospital, Vancouver, BC, Canada. SVercauteren2@cw.bc.ca.|Child & Family Research Institute, Vancouver, BC, Canada. SVercauteren2@cw.bc.ca.
authors.forename: S
authors.initials: S
authors.lastname: Vercauteren
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual / Q000097:blood / Q000175:diagnosis / Q000628:therapy; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000628:therapy*
keywords: Acute lymphoblastic leukemia; flow cytometry; minimal residual disease