DETECTION OF MINIMAL RESIDUAL DISEASE IN B-LINEAGE ACUTE LYMPHOBLASTIC-LEUKEMIA BY QUANTITATIVE FLOW-CYTOMETRY

The clinical significance of detecting minimal residual disease (MRD) in B-lineage acute lymphoblastic leukaemia (ALL) was evaluated by quan titative 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 re lapsed and MRD had been detected in six of them, 5-15 weeks before rel apse despite morphological complete remission, 43 patients remain in c linical remission and in none of these was MRD detected. Disease-free survival based on the detection of MRD by flow cytometry showed a stat istically significant difference between both groups (P<0.0001). The a bsence of MRD correlates with a low relapse rate, whereas the presence of MRD predicted early relapse, This study has shown that flow cytome try can improve the morphologic assessment of bone marrow (BM) remissi on 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 r esidual leukaemic blasts were detected by flow cytometry in nine sampl es from six patients. On the other hand, the presence of > 5% blasts a ssessed by morphology was not necessarily a feature of relapse in five patients as these cells were shown to have a phenotype identical to n ormal TdT-negative B-cell precursors. Quantitative now cytometry was m ore informative than conventional morphology to assess remission statu s and showed a strong correlation with clinical outcome. This methodol ogy is useful to define MRD in the majority of patients with B-lineage ALL and should be tested in prospective clinical trials.