title: Critical evaluation of ASO RQ-PCR for minimal residual disease evaluation in multiple myeloma. A comparative analysis with flow cytometry.
abstract: We have analyzed the applicability, sensitivity and prognostic value of allele-specific oligonucleotide real-time quantitative PCR (ASO RQ-PCR) as a method for minimal residual disease (MRD) assessment in patients with multiple myeloma (MM), comparing the results with those of multiparameter flow cytometry (MFC). A total of 170 patients enrolled in three consecutive Spanish trials achieving at least partial response after treatment were included. Lack of clonality detection (n=31), unsuccessful sequencing (n=17) and suboptimal ASO performance (n=51) limited the applicability of PCR to 42% of cases. MRD was finally investigated in 103 patients (including 32 previously studied) with persistent disease identified by PCR and MFC in 54% and 46% of cases, respectively. A significant correlation in MRD quantitation by both the techniques was noted (r=0.881, P<0.001), being reflective of treatment intensity. Patients with <10(-4) residual tumor cells showed longer progression-free survival (PFS) compared with the rest (not reached (NR) vs 31 months, P=0.002), with similar results observed with MFC. Among complete responders (n=62), PCR discriminated two risk groups with different PFS (49 vs 26 months, P=0.001) and overall survival (NR vs 60 months, P=0.008). Thus, although less applicable than MFC, ASO RQ-PCR is a powerful technique to assess treatment efficacy and risk stratification in MM.
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca; IBSAL; IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Puig
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca; IBSAL; IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: M E
authors.initials: ME
authors.lastname: Sarasquete
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca; IBSAL; IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Balanzategui
authors.affiliation: Department of Hematology, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Martínez
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca; IBSAL; IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Paiva
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca; IBSAL; IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: H
authors.initials: H
authors.lastname: García
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca; IBSAL; IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Fumero
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca; IBSAL; IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Jiménez
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca; IBSAL; IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Alcoceba
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca; IBSAL; IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Chillón
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca; IBSAL; IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Sebastián
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca; IBSAL; IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Marín
authors.affiliation: Department of Hematology, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Montalbán
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca; IBSAL; IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: M V
authors.initials: MV
authors.lastname: Mateos
authors.affiliation: Department of Hematology, Hospital Germans Trias I Pujol, Badalona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Oriol
authors.affiliation: Department of Hematology, Hospital Clínico 'Lozano Blesa', Zaragoza, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Palomera
authors.affiliation: Department of Hematology, Hospital Universitario La Fe and Universidad Católica 'San Vicente Mártir', Valencia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: de la Rubia
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca; IBSAL; IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: M B
authors.initials: MB
authors.lastname: Vidriales
authors.affiliation: Department of Hematology, Hospital Clinic I Provincial, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Bladé
authors.affiliation: Department of Hematology, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: Lahuerta
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca; IBSAL; IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: M
authors.initials: M
authors.lastname: González
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca; IBSAL; IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: J F S
authors.initials: JF
authors.lastname: Miguel
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca; IBSAL; IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: R
authors.initials: R
authors.lastname: García-Sanz
mesh_terms: D000483:Alleles; D005434:Flow Cytometry; D015322:Gene Rearrangement, B-Lymphocyte; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D009101:Multiple Myeloma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D007143:Immunoglobulin Heavy Chains; D007145:Immunoglobulin kappa-Chains