Minimal residual disease assessed by multi-parameter flow cytometry is highly prognostic in adult patients with acute lymphoblastic leukaemia

The prognostic value of minimal residual disease (MRD) assessed by multi-parameter flow cytometry (MFC) was investigated among 340 adult patients with B-cell acute lymphoblastic leukaemia (B-ALL) treated between2004 and 2014 using regimens including the hyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine) backbone. Among them, 323 (95%) achieved complete remission (CR) and were included in this study. Median age was 52years (range, 15-84). Median white blood cell count (WBC) was 935x10(9)/l (range, 04-6581x10(9)/l). MRD by MFC was initially assessed with a sensitivity of 001%, using a 15-marker, 4-colour panel and subsequently a 6-colour panel on bone marrow specimens obtained at CR achievement and at approximately 3month intervals thereafter. MRD negative status at CR was associated with improved disease-free survival (DFS) and overall survival (OS) (P=0004 and P=003, respectively). Similarly, achieving MRD negative status at approximately 3 and 6months was associated with improved DFS (P=0004 and P<00001, respectively) and OS (P=0004 and P<00001, respectively). Multivariate analysis including age, WBC at presentation, cytogenetics (standard versus high risk) and MRD status at CR, 3 and 6months, indicated that MRD negative status at CR was an independent predictor of DFS (P<005). Achievement of an MRD negative state assessed by MFC is an important predictor of DFS and OS in adult patients with ALL.