Minimal residual disease monitoring in multiple myeloma: a comparison between allelic-specific oligonucleotide real-time quantitative polymerase chain reaction and flow cytometry

• Published in: Haematologica (Roma) 2005-10, Vol.90 (10), p.1365-1372
• Main Authors: Sarasquete, ME, Garcia-Sanz, R, Gonzalez, D, Martinez, J, Mateo, G, Martinez, P, Ribera, JM, Hernandez, JM, Lahuerta, JJ, Orfao, A, Gonzalez, M, San Miguel, JF
• Format: Article
• Language: English
• Subjects: Aged; Alleles; Biological and medical sciences; Bone Marrow Cells - pathology; Flow Cytometry; Hematologic and hematopoietic diseases; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Middle Aged; Multiple Myeloma - diagnosis; Multiple Myeloma - genetics; Multiple Myeloma - pathology; Neoplasm, Residual; Oligonucleotides; Polymerase Chain Reaction
• ISSN: 0390-6078; 1592-8721

Grupo Espanol de Mieloma (GEM-PETHEMA), Red Espanola de Mieloma (G03/136), Servicio de Hematologia, Hospital Universitario de Salamanca, Centro de Investigacion del Cancer (CIC), Universidad de Salamanca, Spain. BACKGROUND AND OBJECTIVES: 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). DESIGN AND 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). INTERPRETATION AND 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.