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Minimal residual disease assessed by multi‐parameter flow cytometry is highly prognostic in adult patients with acute lymphoblastic leukaemia
Authors:Farhad Ravandi  Jeffrey L. Jorgensen  Susan M. O'Brien  Elias Jabbour  Deborah A. Thomas  Gautam Borthakur  Rebecca Garris  Xuelin Huang  Guillermo Garcia‐Manero  Jan A. Burger  Alessandra Ferrajoli  William Wierda  Tapan Kadia  Nitin Jain  Sa A. Wang  Sergei Konoplev  Partow Kebriaei  Richard E. Champlin  Deborah McCue  Zeev Estrov  Jorge E. Cortes  Hagop M. Kantarjian
Affiliation:1. Departments of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;2. Departments of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;3. Departments of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;4. Departments of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;5. Departments of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Abstract: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 between 2004 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 52 years (range, 15–84). Median white blood cell count (WBC) was 9·35 × 109/l (range, 0·4–658·1 ×1 09/l). MRD by MFC was initially assessed with a sensitivity of 0·01%, using a 15‐marker, 4‐colour panel and subsequently a 6‐colour panel on bone marrow specimens obtained at CR achievement and at approximately 3 month intervals thereafter. MRD negative status at CR was associated with improved disease‐free survival (DFS) and overall survival (OS) (P = 0·004 and P = 0·03, respectively). Similarly, achieving MRD negative status at approximately 3 and 6 months was associated with improved DFS (P = 0·004 and P < 0·0001, respectively) and OS (P = 0·004 and P < 0·0001, respectively). Multivariate analysis including age, WBC at presentation, cytogenetics (standard versus high risk) and MRD status at CR, 3 and 6 months, indicated that MRD negative status at CR was an independent predictor of DFS (P < 0·05). Achievement of an MRD negative state assessed by MFC is an important predictor of DFS and OS in adult patients with ALL.
Keywords:minimal residual disease  acute leukaemia  flow cytometry
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