title: Minimal residual disease monitoring in multiple myeloma: a comparison between allelic-specific oligonucleotide real-time quantitative polymerase chain reaction and flow cytometry.
abstract: OBJECTIVE
  Minimal residual disease (MRD) studies are useful in multiple myeloma (MM). However, the definition of the best technique and clinical utility are still unresolved issues. The aim of this study was to analyze and compare the clinical utility of MRD studies in MM with two different techniques: allelic-specific oligonucleotide real-time quantitative PCR (ASO-RQ-PCR), and flow cytometry (FCM).
  
  
  METHODS
  Bone marrow samples from 32 MM patients who had achieved complete response after transplantation were evaluated by ASO-RQ-PCR, using TaqMan technology, and multiparametric FCM.
  
  
  RESULTS
  ASO-RQ-PCR was only applicable in 75% of patients for a variety of technical reasons, while FCM was applicable in up to 90%. Therefore, simultaneous PCR/FCM analysis was possible in only 24 patients. The number of residual tumor cells identified by both techniques was very similar (mean=0.29%, range=0.001-1.61%, correlation coefficient=0.861). However, RQ-PCR was able to detect residual myelomatous cells in 17 patients while FCM only did so in 11; thus, 6 cases were FCM negative but PCR positive, all of them displaying a very low number of clonal cells (median=0.014%, range=0.001-0.11). Using an MRD threshold of 0.01% (10(-4)) two risk groups with significantly different progression-free survival could be identified by either PCR (34 vs. 15m, p=0.04) or FCM (27 vs. 10m, p=0.05).
  
  
  CONCLUSIONS
  Although MRD evaluation by ASO-RQ-PCR is slightly more sensitive and specific than FCM, it is applicable in a lower proportion of MM patients and is more time-consuming, while both techniques provide similar prognostic information.
authors.affiliation: Grupo Español de Mieloma (GEM-PETHEMA), Red Española de Mieloma (G03/136), Servicio de Hematología, Hospital Universitario de Salamanca, Centro de Investigación del Cáncer (CIC), Universidad de Salamanca, Spain.
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Sarasquete
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Sanz
authors.forename: David
authors.initials: D
authors.lastname: González
authors.forename: Joaquín
authors.initials: J
authors.lastname: Martínez
authors.forename: Gema
authors.initials: G
authors.lastname: Mateo
authors.forename: Pilar
authors.initials: P
authors.lastname: Martínez
authors.forename: José Maria
authors.initials: JM
authors.lastname: Ribera
authors.forename: José Mariano
authors.initials: JM
authors.lastname: Hernández
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Lahuerta
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfão
authors.forename: Marcos
authors.initials: M
authors.lastname: González
authors.forename: Jesus F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D000368:Aged; D000483:Alleles; D001854:Bone Marrow Cells / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D018365:Neoplasm, Residual; D009841:Oligonucleotides; D016133:Polymerase Chain Reaction
chemical_list: D009841:Oligonucleotides