title: Detection of minimal residual disease in B-lineage acute lymphoblastic leukaemia by quantitative flow cytometry.
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.
authors.affiliation: Academic Department of Haematology and Cytogenetics, The Royal Marsden NHS Trust and Institute of Cancer Research, London.
authors.forename: N
authors.initials: N
authors.lastname: Farahat
authors.forename: A
authors.initials: A
authors.lastname: Morilla
authors.forename: K
authors.initials: K
authors.lastname: Owusu-Ankomah
authors.forename: R
authors.initials: R
authors.lastname: Morilla
authors.forename: C R
authors.initials: CR
authors.lastname: Pinkerton
authors.forename: J G
authors.initials: JG
authors.lastname: Treleaven
authors.forename: E
authors.initials: E
authors.lastname: Matutes
authors.forename: R L
authors.initials: RL
authors.lastname: Powles
authors.forename: D
authors.initials: D
authors.lastname: Catovsky
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000379:methods*; D002051:Burkitt Lymphoma / Q000175:diagnosis* / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D008297:Male; D018365:Neoplasm, Residual / Q000175:diagnosis*; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome