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.
Br J Haematol
; 158(2): 186-197, 2012 Jul.
Article
in En
| MEDLINE
| ID: mdl-22626453
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Immunoglobulin Heavy Chains
/
Lymphoma, Mantle-Cell
/
V(D)J Recombination
Type of study:
Clinical_trials
/
Guideline
/
Prognostic_studies
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Br J Haematol
Year:
2012
Document type:
Article
Affiliation country:
France