title: Cloned IGH VDJ targets as tools for personalized minimal residual disease monitoring in mature lymphoid malignancies; a feasibility study in mantle cell lymphoma by the Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang.
abstract: Molecular minimal residual disease (MRD) analysis is fast emerging as an essential clinical decision-making tool for the treatment and follow-up of mature B cell malignancies. Current EuroMRD consensus IGH real-time quantitative polymerase chain reaction RQ-PCR assays rely on flow cytometric assessment of diagnostic tumour burdens to construct 'normalized', patient-specific, diagnostic DNA-based MRD quantification standards. Here, we propose a new 'hybrid' assay that relies on plasmid-based quantification of patient-specific IGH VDJ targets by consensus IGH real time (RQ)-PCR, combined with EuroMRD guidelines, for MRD monitoring in lymphoid malignancies. This assay was evaluated for MRD assessment in a total of 273 samples from 29 mantle cell lymphoma (MCL) patients treated within a Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang (GOELAMS) Phase II trial and was feasible, reliable and consistently comparable to gold-standard MRD techniques (99% concordance across all samples including 32 samples within the quantitative range) when analysed in parallel (117 samples). Integrating clinical prognostic parameters and MRD status in peripheral blood at the post-induction stage was predictive of progression-free survival (P = 0·034) thus demonstrating the clinical utility of the approach. Plasmid-based standards for the quantification of IGH VDJ targets are therefore confirmed to offer new opportunities for further standardization and clinical evaluation of MRD-guided management of patients with mature B cell malignancies.
authors.affiliation: INSERM U823, Institut Albert Bonniot, Grenoble, France.|Université Joseph Fourier-Grenoble I, Institut Albert Bonniot, Grenoble, France.|Plateforme de génétique moléculaire des cancers, Pôle de Biologie, CHU de Grenoble, Grenoble, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Gimenez
authors.affiliation: INSERM U823, Institut Albert Bonniot, Grenoble, France.|Université Joseph Fourier-Grenoble I, Institut Albert Bonniot, Grenoble, France.|Plateforme de génétique moléculaire des cancers, Pôle de Biologie, CHU de Grenoble, Grenoble, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Chauvet
authors.affiliation: Plateforme de génétique moléculaire des cancers, Pôle de Biologie, CHU de Grenoble, Grenoble, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Rabin
authors.affiliation: Plateforme de génétique moléculaire des cancers, Pôle de Biologie, CHU de Grenoble, Grenoble, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Puteaud
authors.affiliation: INSERM U823, Institut Albert Bonniot, Grenoble, France.|Université Joseph Fourier-Grenoble I, Institut Albert Bonniot, Grenoble, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Duley
authors.affiliation: INSERM U823, Institut Albert Bonniot, Grenoble, France.|Université Joseph Fourier-Grenoble I, Institut Albert Bonniot, Grenoble, France.|Pôle recherche, CHU de Grenoble, Grenoble, France.
authors.forename: Sieme
authors.initials: S
authors.lastname: Hamaidia
authors.affiliation: INSERM U823, Institut Albert Bonniot, Grenoble, France.|Université Joseph Fourier-Grenoble I, Institut Albert Bonniot, Grenoble, France.
authors.forename: Juliana
authors.initials: J
authors.lastname: Bruder
authors.affiliation: Pôle recherche, CHU de Grenoble, Grenoble, France.|Pôle de Cancérologie et d'Hématologie, CHU de Grenoble, Grenoble, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Rolland-Neyret
authors.affiliation: Service d'Hématologie clinique, CHU de Nantes, Nantes, France.
authors.forename: Steven
authors.initials: S
authors.lastname: Le Gouill
authors.affiliation: Hématologie, Hôtel Dieu, CHU de Clermont Ferrand, Boulevard Leon Malfreyt, Clermont Ferrand, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Tournilhac
authors.affiliation: Service d'Hématologie, Clinique Victor Hugo, 1 rue Victor Hugo, Le Mans, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Voog
authors.affiliation: Service d'Hématologie, La Roche sur Yon, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Maisonneuve
authors.affiliation: INSERM U823, Institut Albert Bonniot, Grenoble, France.|Université Joseph Fourier-Grenoble I, Institut Albert Bonniot, Grenoble, France.|Laboratoire d'immunologie cellulaire, CHU de Grenoble, Grenoble, France.
authors.forename: Marie C
authors.initials: MC
authors.lastname: Jacob
authors.affiliation: INSERM U823, Institut Albert Bonniot, Grenoble, France.|Université Joseph Fourier-Grenoble I, Institut Albert Bonniot, Grenoble, France.|Plateforme de génétique moléculaire des cancers, Pôle de Biologie, CHU de Grenoble, Grenoble, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Leroux
authors.affiliation: Immunologie, CHU de Nancy & Nancy Université, Vandoeuvre les Nancy, France.
authors.forename: Marie C
authors.initials: MC
authors.lastname: Béné
authors.affiliation: Faculté de Médecine, Université de la Méditerranée, Marseille, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Formisano-Tréziny
authors.affiliation: Faculté de Médecine, Université de la Méditerranée, Marseille, France.|Laboratoire de Biologie Moléculaire, Hôpital Nord, Marseille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Gabert
authors.affiliation: INSERM U823, Institut Albert Bonniot, Grenoble, France.|Université Joseph Fourier-Grenoble I, Institut Albert Bonniot, Grenoble, France.|Pôle de Cancérologie et d'Hématologie, CHU de Grenoble, Grenoble, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Gressin
authors.affiliation: INSERM U823, Institut Albert Bonniot, Grenoble, France.|Université Joseph Fourier-Grenoble I, Institut Albert Bonniot, Grenoble, France.|Plateforme de génétique moléculaire des cancers, Pôle de Biologie, CHU de Grenoble, Grenoble, France.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Callanan
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000235:genetics; D018572:Disease-Free Survival; D005240:Feasibility Studies; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D020522:Lymphoma, Mantle-Cell / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D010957:Plasmids / Q000235:genetics; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D060152:V(D)J Recombination / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D007143:Immunoglobulin Heavy Chains