Detection of minimal residual disease in B-lineage acute lymphoblastic leukaemia by quantitative flow cytometry

Authors: Farahat, Nahla1; Morilla, Alison1; Owusu-Ankomah, Kwasi1; Morilla, Ricardo1; Pinkerton, C. Ross2; Treleaven, Jennie G.1; Matutes, Estella1; Powles, Ray L.3; Catovsky, Daniel1

Source: British Journal of Haematology, Volume 101, Number 1, April 1998 , pp. 158-164(7)

Publisher: Blackwell Publishing

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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.

Keywords: minimal residual leukaemia; B-lineage ALL; flow cytometry

Document Type: Original article

DOI: 10.1046/j.1365-2141.1998.00675.x

Affiliations: 1: Academic Department of Haematology and Cytogenetics, 2: Paediatric Oncology, 3: Leukaemia Units, The Royal Marsden NHS Trust and Institute of Cancer Research, London and Sutton

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