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Comparative analysis of flow cytometry and polymerase chain reaction for the detection of minimal residual disease in childhood acute lymphoblastic leukemia

Abstract

Minimal residual disease (MRD) is an independent prognostic factor in childhood acute lymphoblastic leukemia (ALL). The most widely applied MRD assays in ALL are flow cytometric identification of leukemia immunophenotypes and polymerase chain reaction (PCR) amplification of antigen-receptor genes. We measured MRD by both assays in 227 patients with childhood B-lineage ALL. Of 1375 samples (736 bone marrow and 639 peripheral blood) examined, MRD was <0.01% in 1200, and 0.01% in 129 by both assays; MRD levels measured by the two methods correlated well. Of the remaining 46 samples, 28 had MRD 0.01% by flow cytometry but <0.01% by PCR. However, PCR (which had a consistent sensitivity of 0.001%) detected leukemic gene rearrangements in 26 of these 28 samples. Conversely, in 18 samples, MRD was 0.01% by PCR but <0.01% by flow cytometry. In nine of these samples, flow cytometry had a sensitivity of 0.001%, and detected aberrant immunophenotypes in eight samples. Therefore, the two most widely used methods for MRD detection in ALL yield concordant results in the vast majority of cases, although the estimated levels of MRD may vary in some. The use of the two methods in tandem ensures MRD monitoring in all patients.

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Acknowledgements

We thank Chris Clark, Peixin Liu, Mo Mehrpooya and Laura Woodruff for excellent technical assistance with MRD studies, and the physicians and nurses of St Jude Children's Research Hospital for continuing support. This work was supported by Grants CA52259, CA60419, and CA21765 from the National Cancer Institute, and by the American Lebanese Syrian Associated Charities (ALSAC). Ching-Hon Pui is the FM Kirby Clinical Research Professor of the American Cancer Society.

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Neale, G., Coustan-Smith, E., Stow, P. et al. Comparative analysis of flow cytometry and polymerase chain reaction for the detection of minimal residual disease in childhood acute lymphoblastic leukemia. Leukemia 18, 934–938 (2004). https://doi.org/10.1038/sj.leu.2403348

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