Detection of minimal residual disease in B-lineage acute lymphoblastic leukaemia by quantitative flow cytometry |
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Authors: | Nahla Farahat,Alison Morilla,Kwasi Owusu-Ankomah,Ricardo Morilla,C. Ross Pinkerton,Jennie G. Treleaven,Estella Matutes,Ray L. Powles,& Daniel Catovsky |
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Affiliation: | Academic Department of Haematology and Cytogenetics,;Paediatric Oncology,;Leukaemia Units, The Royal Marsden NHS Trust and Institute of Cancer Research, London and Sutton |
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Abstract: | The clinical significance of detecting minimal residual disease (MRD) in B-lineage acute lymphoblastic leukaemia (ALL) was evaluated by quantitative flow cytometry using a combination of TdT with CD10 and CD19. 53 patients with B-cell precursor ALL were followed during and after completion of treatment (median follow-up 23 months). Nine patients relapsed and MRD had been detected in six of them, 5–15 weeks before relapse despite morphological complete remission. 43 patients remain in clinical remission and in none of these was MRD detected. Disease-free survival based on the detection of MRD by flow cytometry showed a statistically significant difference between both groups ( P < 0.0001). The absence of MRD correlates with a low relapse rate, whereas the presence of MRD predicted early relapse. This study has shown that flow cytometry can improve the morphologic assessment of bone marrow (BM) remission status in B-lineage ALL. The finding of < 5% blasts in BM aspirates did not correlate with 'true' remission in a proportion of cases as residual leukaemic blasts were detected by flow cytometry in nine samples from six patients. On the other hand, the presence of > 5% blasts assessed by morphology was not necessarily a feature of relapse in five patients as these cells were shown to have a phenotype identical to normal TdT-negative B-cell precursors. Quantitative flow cytometry was more informative than conventional morphology to assess remission status and showed a strong correlation with clinical outcome. This methodology is useful to define MRD in the majority of patients with B-lineage ALL and should be tested in prospective clinical trials. |
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Keywords: | minimal residual leukaemia B-lineage ALL flow cytometry |
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