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Br J Haematol. 2012 Jul;158(2):186-197. doi: 10.1111/j.1365-2141.2012.09161.x. Epub 2012 May 25.

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.

Author information

1
INSERM U823, Institut Albert Bonniot, Grenoble, France.
2
Université Joseph Fourier-Grenoble I, Institut Albert Bonniot, Grenoble, France.
3
Plateforme de génétique moléculaire des cancers, Pôle de Biologie, CHU de Grenoble, Grenoble, France.
4
Pôle recherche, CHU de Grenoble, Grenoble, France.
5
Pôle de Cancérologie et d'Hématologie, CHU de Grenoble, Grenoble, France.
6
Service d'Hématologie clinique, CHU de Nantes, Nantes, France.
7
Hématologie, Hôtel Dieu, CHU de Clermont Ferrand, Boulevard Leon Malfreyt, Clermont Ferrand, France.
8
Service d'Hématologie, Clinique Victor Hugo, 1 rue Victor Hugo, Le Mans, France.
9
Service d'Hématologie, La Roche sur Yon, France.
10
Laboratoire d'immunologie cellulaire, CHU de Grenoble, Grenoble, France.
11
Immunologie, CHU de Nancy & Nancy Université, Vandoeuvre les Nancy, France.
12
Faculté de Médecine, Université de la Méditerranée, Marseille, France.
13
Laboratoire de Biologie Moléculaire, Hôpital Nord, Marseille, France.

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.

[Indexed for MEDLINE]

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