title: Marked Variability in Reported Minimal Residual Disease Lower Level of Detection of 4 Hematolymphoid Neoplasms: A Survey of Participants in the College of American Pathologists Flow Cytometry Proficiency Testing Program.
abstract: BACKGROUND
  Flow cytometry is often applied to minimal residual disease (MRD) testing in hematolymphoid neoplasia. Because flow-based MRD tests are developed in the laboratory, testing methodologies and lower levels of detection (LODs) are laboratory dependent.
  
  
  OBJECTIVE
  To broadly survey flow cytometry laboratories about MRD testing in laboratories, if performed, including indications and reported LODs.
  
  
  METHODS
  Voluntary supplemental questions were sent to the 549 laboratories participating in the College of American Pathologists (CAP) FL3-A Survey (Flow Cytometry-Immunophenotypic Characterization of Leukemia/Lymphoma) in the spring of 2014.
  
  
  RESULTS
  A total of 500 laboratories (91%) responded to the supplemental questions as part of the FL3-A Survey by April 2014; of those 500 laboratories, 167 (33%) currently perform MRD for lymphoblastic leukemia, 118 (24%) for myeloid leukemia, 99 (20%) for chronic lymphocytic leukemia, and 91 (18%) for plasma cell myeloma. Other indications include non-Hodgkin lymphoma, hairy cell leukemia, neuroblastoma, and myelodysplastic syndrome. Most responding laboratories that perform MRD for lymphoblastic leukemia reported an LOD of 0.01%. For myeloid leukemia, chronic lymphocytic leukemia, and plasma cell myeloma, most laboratories indicated an LOD of 0.1%. Less than 3% (15 of 500) of laboratories reported LODs of 0.001% for one or more MRD assays performed.
  
  
  CONCLUSIONS
  There is major heterogeneity in the reported LODs of MRD testing performed by laboratories subscribing to the CAP FL3-A Survey. To address that heterogeneity, changes to the Flow Cytometry Checklist for the CAP Laboratory Accreditation Program are suggested that will include new requirements that each laboratory (1) document how an MRD assay's LOD is measured, and (2) include the LOD or lower limit of enumeration for flow-based MRD assays in the final diagnostic report.
authors.affiliation: From the Department of Hematology, London Health Sciences Centre, London, Ontario, Canada (Mr Keeney); the Department of Surveys, College of American Pathologists, Northfield, Illinois (Ms Halley); the Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (Dr Rhoads); the Department of Clinical Pathology, Cleveland Clinic, Cleveland, Ohio (Dr Ansari); PhenoPath, Seattle, Washington (Dr Kussick); the Department of Laboratory Medicine, University of California, San Francisco (Dr Karlon); Quest Diagnostics, Teterboro, New Jersey (Dr Mehta); the Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (Dr Dorfman); and the Division of Hematopathology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (Dr Linden).
authors.forename: Michael
authors.initials: M
authors.lastname: Keeney
authors.forename: Jaimie G
authors.initials: JG
authors.lastname: Halley
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Rhoads
authors.forename: M Qasim
authors.initials: MQ
authors.lastname: Ansari
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Kussick
authors.forename: William J
authors.initials: WJ
authors.lastname: Karlon
authors.forename: Kumudini U
authors.initials: KU
authors.lastname: Mehta
authors.forename: David M
authors.initials: DM
authors.lastname: Dorfman
authors.forename: Michael A
authors.initials: MA
authors.lastname: Linden
mesh_terms: D005434:Flow Cytometry / Q000379:methods* / Q000592:standards; D006801:Humans; D007753:Laboratories / Q000592:standards; D059021:Laboratory Proficiency Testing / Q000379:methods / Q000592:standards; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis*; D009101:Multiple Myeloma / Q000175:diagnosis*; D018365:Neoplasm, Residual / Q000175:diagnosis*; D010338:Pathology, Clinical / Q000379:methods / Q000592:standards; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012955:Societies, Medical; D011795:Surveys and Questionnaires; D014481:United States