Minimal residual disease monitoring in multiple myeloma: a comparison between allelic-specific oligonucleotide real-time quantitative polymerase chain reaction and flow cytometry.
OBJECTIVE
Minimal residual disease (MRD) studies are useful in multiple myeloma (MM). However, the definition of the best technique and clinical utility are still unresolved issues. The aim of this study was to analyze and compare the clinical utility of MRD studies in MM with two different techniques: allelic-specific oligonucleotide real-time quantitative PCR (ASO-RQ-PCR), and flow cytometry (FCM).


METHODS
Bone marrow samples from 32 MM patients who had achieved complete response after transplantation were evaluated by ASO-RQ-PCR, using TaqMan technology, and multiparametric FCM.


RESULTS
ASO-RQ-PCR was only applicable in 75% of patients for a variety of technical reasons, while FCM was applicable in up to 90%. Therefore, simultaneous PCR/FCM analysis was possible in only 24 patients. The number of residual tumor cells identified by both techniques was very similar (mean=0.29%, range=0.001-1.61%, correlation coefficient=0.861). However, RQ-PCR was able to detect residual myelomatous cells in 17 patients while FCM only did so in 11; thus, 6 cases were FCM negative but PCR positive, all of them displaying a very low number of clonal cells (median=0.014%, range=0.001-0.11). Using an MRD threshold of 0.01% (10(-4)) two risk groups with significantly different progression-free survival could be identified by either PCR (34 vs. 15m, p=0.04) or FCM (27 vs. 10m, p=0.05).


CONCLUSIONS
Although MRD evaluation by ASO-RQ-PCR is slightly more sensitive and specific than FCM, it is applicable in a lower proportion of MM patients and is more time-consuming, while both techniques provide similar prognostic information.
Sarasquete
María Eugenia
ME
Grupo Español de Mieloma (GEM-PETHEMA), Red Española de Mieloma (G03/136), Servicio de Hematología, Hospital Universitario de Salamanca, Centro de Investigación del Cáncer (CIC), Universidad de Salamanca, Spain.
García-Sanz
Ramón
R
González
David
D
Martínez
Joaquín
J
Mateo
Gema
G
Martínez
Pilar
P
Ribera
José Maria
JM
Hernández
José Mariano
JM
Lahuerta
Juan José
JJ
Orfão
Alberto
A
González
Marcos
M
San Miguel
Jesus F
JF
D000368:Aged; D000483:Alleles; D001854:Bone Marrow Cells / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D018365:Neoplasm, Residual; D009841:Oligonucleotides; D016133:Polymerase Chain Reaction
D009841:Oligonucleotides