期刊
BRITISH JOURNAL OF HAEMATOLOGY
卷 158, 期 2, 页码 186-197出版社
WILEY
DOI: 10.1111/j.1365-2141.2012.09161.x
关键词
minimal residual disease; plasmid-based MRD standards; rituximab; autologous stem cell transplantation; mantle cell lymphoma
类别
资金
- GOELAMS
- DRCI of the CHU de Grenoble
- French MCL network (INCa)
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 Leucemies 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.
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