Concurrent detection of minimal residual disease (MRD) in childhood acute lymphoblastic leukaemia by flow cytometry and real-time PCR
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Concurrent detection of minimal residual disease (MRD) in childhood acute lymphoblastic leukaemia by flow cytometry and real-time PCR. / Kerst, Gunter; Kreyenberg, Hermann; Roth, Carmen; Well, Catrin; Dietz, Klaus; Coustan-Smith, Elaine; Campana, Dario; Koscielniak, Ewa; Niemeyer, Charlotte; Schlegel, Paul G; Müller, Ingo; Niethammer, Dietrich; Bader, Peter.
in: BRIT J HAEMATOL, Jahrgang 128, Nr. 6, 03.2005, S. 774-82.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Concurrent detection of minimal residual disease (MRD) in childhood acute lymphoblastic leukaemia by flow cytometry and real-time PCR
AU - Kerst, Gunter
AU - Kreyenberg, Hermann
AU - Roth, Carmen
AU - Well, Catrin
AU - Dietz, Klaus
AU - Coustan-Smith, Elaine
AU - Campana, Dario
AU - Koscielniak, Ewa
AU - Niemeyer, Charlotte
AU - Schlegel, Paul G
AU - Müller, Ingo
AU - Niethammer, Dietrich
AU - Bader, Peter
PY - 2005/3
Y1 - 2005/3
N2 - Minimal (i.e. submicroscopic) residual disease (MRD) predicts outcome in childhood acute lymphoblastic leukaemia (ALL). To be used clinically, MRD assays must be reliable and accurate. Two well-established techniques, flow cytometry (FC) and polymerase chain reaction (PCR), can detect leukaemic cells with a sensitivity of 0.01% (10(-4)). We analysed diagnostic samples of 45 ALL-patients (37 B-lineage ALL, eight T-lineage ALL) by four-colour FC and real-time PCR. Leukaemia-associated immunophenotypes, at a sensitivity of MRD detection by FC at the 0.01% level, were identified in 41 cases (91%); antigen-receptor gene rearrangements suitable for MRD detection with a sensitivity of 0.01% or better by PCR were identified in 38 cases (84%). The combined use of FC and PCR allowed MRD monitoring in all 45 patients. In 105 follow-up samples, MRD estimates by both methods were highly concordant, with a deviation factor of <5 by Bland-Altman analysis. Importantly, the concordance between FC and PCR was also observed in regenerating bone marrow samples containing high proportions of CD19(+) cells, and in samples studied 24 h after collection. We conclude that both MRD assays yield generally concordant results. Their combined use should enable MRD monitoring in virtually all patients and prevent false-negative results due to clonal evolution or phenotypic shifts.
AB - Minimal (i.e. submicroscopic) residual disease (MRD) predicts outcome in childhood acute lymphoblastic leukaemia (ALL). To be used clinically, MRD assays must be reliable and accurate. Two well-established techniques, flow cytometry (FC) and polymerase chain reaction (PCR), can detect leukaemic cells with a sensitivity of 0.01% (10(-4)). We analysed diagnostic samples of 45 ALL-patients (37 B-lineage ALL, eight T-lineage ALL) by four-colour FC and real-time PCR. Leukaemia-associated immunophenotypes, at a sensitivity of MRD detection by FC at the 0.01% level, were identified in 41 cases (91%); antigen-receptor gene rearrangements suitable for MRD detection with a sensitivity of 0.01% or better by PCR were identified in 38 cases (84%). The combined use of FC and PCR allowed MRD monitoring in all 45 patients. In 105 follow-up samples, MRD estimates by both methods were highly concordant, with a deviation factor of <5 by Bland-Altman analysis. Importantly, the concordance between FC and PCR was also observed in regenerating bone marrow samples containing high proportions of CD19(+) cells, and in samples studied 24 h after collection. We conclude that both MRD assays yield generally concordant results. Their combined use should enable MRD monitoring in virtually all patients and prevent false-negative results due to clonal evolution or phenotypic shifts.
KW - Adolescent
KW - Biomarkers, Tumor
KW - Child
KW - Child, Preschool
KW - Flow Cytometry
KW - Gene Rearrangement, T-Lymphocyte
KW - Humans
KW - Infant
KW - Neoplasm, Residual
KW - Phenotype
KW - Polymerase Chain Reaction
KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma
KW - Sensitivity and Specificity
U2 - 10.1111/j.1365-2141.2005.05401.x
DO - 10.1111/j.1365-2141.2005.05401.x
M3 - SCORING: Journal article
C2 - 15755280
VL - 128
SP - 774
EP - 782
JO - BRIT J HAEMATOL
JF - BRIT J HAEMATOL
SN - 0007-1048
IS - 6
ER -