Standardized MRD flow and ASO IGH RQ-PCR for MRD quantification in CLL patients after rituximab-containing immunochemotherapy: a comparative analysis

• Published in: Leukemia Vol. 23; no. 11; pp. 2007 - 2017
• Main Authors: Böttcher, S, Stilgenbauer, S, Busch, R, Brüggemann, M, Raff, T, Pott, C, Fischer, K, Fingerle-Rowson, G, Döhner, H, Hallek, M, Kneba, M, Ritgen, M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2009; Nature Publishing Group
• Subjects: Aged; Aged, 80 and over; Antibodies; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents - therapeutic use; B-Lymphocytes - cytology; B-Lymphocytes - drug effects; Biological and medical sciences; Cancer Research; Care and treatment; Chemotherapy; Chemotherapy, Combination; Chronic lymphocytic leukemia; Comparative analysis; Critical Care Medicine; Drug Monitoring - methods; Drug Monitoring - standards; Female; Flow cytometry; Flow Cytometry - methods; Flow Cytometry - standards; Genetic aspects; Health aspects; Heavy chains; Hematologic and hematopoietic diseases; Hematology; Humans; Immunoglobulins; Intensive; Internal Medicine; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Limit of Detection; Lymphatic leukemia; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Minimal residual disease; Neoplasm, Residual - diagnosis; Neoplasm, Residual - drug therapy; Oncology; original-article; Polymerase chain reaction; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Rituximab; Sensitivity; Sensitivity and Specificity; Stem cells; Transplantation; Germany; CLL; minimal residual disease; MRD flow; rituximab; real-time quantitative PCR; Antineoplastic agent; Human; Heavy peptide chain; Immunochemotherapy; Immunoglobulins; Hematology; Minimal residual disease; Rituximab; Malignant hemopathy; Monoclonal antibody; Real time; Polymerase chain reaction; Chemotherapy; Chronic lymphocytic leukemia; Treatment; Lymphoproliferative syndrome; Immunotherapy; Molecular biology; Comparative study; Cancer; Quantitative analysis
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2009.140

Rituximab-containing regimens are becoming a therapeutic standard in chronic lymphocytic leukemia (CLL), so that a validation of flow cytometric minimal residual disease (MRD) quantification (MRD flow) in the presence of this antibody is necessary. We therefore compared results obtained by real-time quantitative (RQ)-PCR to MRD flow in 530 samples from 69 patients randomized to receive chemotherapy or chemotherapy plus rituximab. Quantitative MRD levels assessed by both techniques were closely correlated irrespective of therapy ( r =0.95). The sensitivity and specificity of MRD flow was not influenced by the presence of rituximab. With 58.9% positive and 26.4% negative samples by both techniques, 85.3% of assessments (452/530) were qualitatively concordant between MRD flow and RQ-PCR. Discordant samples were typically negative by MRD flow and simultaneously positive close to the detection limit of the PCR assays, indicating a higher sensitivity of PCR for very low MRD levels. However, 93.8% of all samples were concordantly classified by both methods using a threshold of 10 −4 to determine MRD positivity. MRD flow and PCR are equally effective for MRD quantification in rituximab-treated CLL patients within a sensitivity range of up to 10 −4 , whereas PCR is more sensitive for detecting MRD below that level.