Flow cytometry and IG/TCR quantitative PCR for minimal residual disease quantitation in acute lymphoblastic leukemia: a French multicenter prospective study on behalf of the FRALLE, EORTC and GRAALL.

Fiche publication


Date publication

février 2013

Auteurs

Membres identifiés du Cancéropôle Est :
Pr GARNACHE-OTTOU Francine


Tous les auteurs :
Garand R, Beldjord K, Cave H, Fossat C, Arnoux I, Asnafi V, Bertrand Y, Boulland ML, Brouzes C, Clappier E, Delabesse E, Fest T, Garnache-Ottou F, Huguet F, Jacob MC, Kuhlein E, Marty-Gres S, Plesa A, Robillard N, Roussel M, Tkaczuk J, Dombret H, Macintyre E, Ifrah N, Bene MC, Baruchel A

Résumé

Minimal residual disease (MRD) quantification is widely used for therapeutic stratification in pediatric acute lymphoblastic leukemia (ALL). A robust, reproducible, sensitivity of at least 0.01% has been achieved for IG/TCR clonal rearrangements using allele-specific quantitative PCR (IG/TCR-QPCR) within the EuroMRD consortium. Whether multiparameter flow cytometry (MFC) can reach such inter-center performance in ALL MRD monitoring remains unclear. In a multicenter study, MRD was measured prospectively on 598 follow-up bone marrow samples from 102 high-risk children and 136 adult ALL patients, using IG/TCR-QPCR and 4/5 color MFC. At diagnosis, all 238 patients (100%) had at least one suitable MRD marker with 0.01% sensitivity, including 205/238 samples (86%) by using IG/TCR-QPCR and 223/238 samples (94%) by using MFC. QPCR and MFC were evaluable in 495/598 (83%) samples. Qualitative results (/=0.01%) concurred in 96% of samples and overall positivity (including /=0.01% correlated highly (r(2)=0.87) and 69% clustered within half-a-log(10). QPCR and MFC can therefore be comparable if properly standardized, and are highly complementary. MFC strategies will benefit from a concerted approach, as does molecular MRD monitoring, and will contribute significantly to the achievement of 100% MRD informativity in adult and pediatric ALL.

Référence

Leukemia. 2013 Feb;27(2):370-6