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Improved flow cytometric detection of minimal residual disease in childhood acute lymphoblastic leukemia

(2013) LEUKEMIA. 27(3). p.635-641
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Abstract
Most current treatment protocols for acute lymphoblastic leukemia (ALL) include minimal residual disease (MRD) diagnostics, generally based on PCR analysis of rearranged antigen receptor genes. Although flow cytometry (FCM) can be used for MRD detection as well, discordant FCM and PCR results are obtained in 5–20% of samples. We evaluated whether 6-color FCM, including additional markers and new marker combinations, improved the results. Bone marrow samples were obtained from 363 ALL patients at day 15, 33 and 78 and MRD was analyzed using 6-color (218 patients) or 4-color (145 patients) FCM in parallel to routine PCR-based MRD diagnostics. Compared with 4-color FCM, 6-color FCM significantly improved the concordance with PCR-based MRD data (88% versus 96%); particularly the specificity of the MRD analysis improved. However, PCR remained more sensitive at levels <0.01%. MRD-based risk groups were similar between 6-color FCM and PCR in 68% of patients, most discrepancies being medium risk by PCR and standard risk by FCM. Alternative interpretation of the PCR data, aimed at prevention of false-positive MRD results, changed the risk group to standard risk in half (52%) of these discordant cases. In conclusion, 6-color FCM significantly improves MRD analysis in ALL but remains less sensitive than PCR-based MRD-diagnostics.
Keywords
acute lymphoblastic leukemia, childhood, flow cytometry, minimal residual disease, real-time quantitative PCR, POLYMERASE-CHAIN-REACTION, TIME QUANTITATIVE PCR, IG/TCR GENE REARRANGEMENTS, PRECURSOR-B-ALL, CONCERTED ACTION REPORT, T-CELL, AIEOP-BFM, IMMUNOPHENOTYPIC MODULATION, INDUCTION THERAPY, BONE-MARROW

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Chicago
Denys, B, AJ van der Sluijs-Gelling, C Homburg, CE van der Schoot , V De Haas, Jan Philippé, R Pieters, J van Dongen, and VHJ van der Velden. 2013. “Improved Flow Cytometric Detection of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia.” Leukemia 27 (3): 635–641.
APA
Denys, B, van der Sluijs-Gelling, A., Homburg, C., van der Schoot , C., De Haas, V., Philippé, J., Pieters, R., et al. (2013). Improved flow cytometric detection of minimal residual disease in childhood acute lymphoblastic leukemia. LEUKEMIA, 27(3), 635–641.
Vancouver
1.
Denys B, van der Sluijs-Gelling A, Homburg C, van der Schoot C, De Haas V, Philippé J, et al. Improved flow cytometric detection of minimal residual disease in childhood acute lymphoblastic leukemia. LEUKEMIA. 2013;27(3):635–41.
MLA
Denys, B, AJ van der Sluijs-Gelling, C Homburg, et al. “Improved Flow Cytometric Detection of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia.” LEUKEMIA 27.3 (2013): 635–641. Print.
@article{3033428,
  abstract     = {Most current treatment protocols for acute lymphoblastic leukemia (ALL) include minimal residual disease (MRD) diagnostics, generally based on PCR analysis of rearranged antigen receptor genes. Although flow cytometry (FCM) can be used for MRD detection as well, discordant FCM and PCR results are obtained in 5–20% of samples. We evaluated whether 6-color FCM, including additional markers and new marker combinations, improved the results. Bone marrow samples were obtained from 363 ALL patients at day 15, 33 and 78 and MRD was analyzed using 6-color (218 patients) or 4-color (145 patients) FCM in parallel to routine PCR-based MRD diagnostics. Compared with 4-color FCM, 6-color FCM significantly improved the concordance with PCR-based MRD data (88% versus 96%); particularly the specificity of the MRD analysis improved. However, PCR remained more sensitive at levels <0.01%. MRD-based risk groups were similar between 6-color FCM and PCR in 68% of patients, most discrepancies being medium risk by PCR and standard risk by FCM. Alternative interpretation of the PCR data, aimed at prevention of false-positive MRD results, changed the risk group to standard risk in half (52%) of these discordant cases. In conclusion, 6-color FCM significantly improves MRD analysis in ALL but remains less sensitive than PCR-based MRD-diagnostics.},
  author       = {Denys, B and van der Sluijs-Gelling, AJ and Homburg, C and van der Schoot , CE and De Haas, V and Philippé, Jan and Pieters, R and van Dongen, J and van der Velden, VHJ},
  issn         = {0887-6924},
  journal      = {LEUKEMIA},
  keywords     = {acute lymphoblastic leukemia,childhood,flow cytometry,minimal residual disease,real-time quantitative PCR,POLYMERASE-CHAIN-REACTION,TIME QUANTITATIVE PCR,IG/TCR GENE REARRANGEMENTS,PRECURSOR-B-ALL,CONCERTED ACTION REPORT,T-CELL,AIEOP-BFM,IMMUNOPHENOTYPIC MODULATION,INDUCTION THERAPY,BONE-MARROW},
  language     = {eng},
  number       = {3},
  pages        = {635--641},
  title        = {Improved flow cytometric detection of minimal residual disease in childhood acute lymphoblastic leukemia},
  url          = {http://dx.doi.org/10.1038/leu.2012.231},
  volume       = {27},
  year         = {2013},
}

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