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.
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% or ≥0.01%) concurred in 96% of samples and overall positivity (including <0.01% and nonquantifiable positivity) was concurrent in 84%. MRD values ≥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.
CHU Nantes, Nantes, France.
R
R
Garand
K
K
Beldjord
H
H
Cavé
C
C
Fossat
I
I
Arnoux
V
V
Asnafi
Y
Y
Bertrand
M-L
ML
Boulland
C
C
Brouzes
E
E
Clappier
E
E
Delabesse
T
T
Fest
F
F
Garnache-Ottou
F
F
Huguet
M-C
MC
Jacob
E
E
Kuhlein
S
S
Marty-Grès
A
A
Plesa
N
N
Robillard
M
M
Roussel
J
J
Tkaczuk
H
H
Dombret
E
E
Macintyre
N
N
Ifrah
M C
MC
Béné
A
A
Baruchel
D000328:Adult; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin / Q000235:genetics*; D019672:Genes, T-Cell Receptor / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D015996:Survival Rate
D004273:DNA, Neoplasm