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. 2016 Feb;172(3):392-400.
doi: 10.1111/bjh.13834. Epub 2015 Oct 22.

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

Farhad Ravandi  1 , Jeffrey L Jorgensen  2 , Susan M O'Brien  1 , Elias Jabbour  1 , Deborah A Thomas  1 , Gautam Borthakur  1 , Rebecca Garris  1 , Xuelin Huang  3 , Guillermo Garcia-Manero  1 , Jan A Burger  1 , Alessandra Ferrajoli  1 , William Wierda  1 , Tapan Kadia  1 , Nitin Jain  1 , Sa A Wang  2 , Sergei Konoplev  2 , Partow Kebriaei  4 , Richard E Champlin  4 , Deborah McCue  5 , Zeev Estrov  1 , Jorge E Cortes  1 , Hagop M Kantarjian  1
Affiliations

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

Farhad Ravandi et al. Br J Haematol. 2016 Feb.

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 × 10(9) /l (range, 0·4-658·1 ×1 0(9) /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: acute leukaemia; flow cytometry; minimal residual disease.

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Figures

Figure 1
Figure 1. Patient disposition and sample collection
a) Patients and sample collection, b) Patient disposition B-ALL, b-cell acute lymphoblastic leukaemia; CR, complete remission; MRD, minimal residual disease; SCT, stem cell transplant.
Figure 2
Figure 2. Outcomes by MRD status at CR, 3 and 6 months from treatment
a) Disease-free survival by flow at CR, b) Overall survival by flow at CR, c) Disease-free survival by flow at 3 months from treatment start date, d) Overall survival by flow at 3 months from treatment start date, e) Disease-free survival by flow at 6 months from treatment start date, f) Overall survival by flow at 6 months from treatment start date All curves are censored at the time of transplant or last follow-up. All the curves are presented from the time of MRD assessment CR, complete remission; MRD, minimal residual disease
Figure 2
Figure 2. Outcomes by MRD status at CR, 3 and 6 months from treatment
a) Disease-free survival by flow at CR, b) Overall survival by flow at CR, c) Disease-free survival by flow at 3 months from treatment start date, d) Overall survival by flow at 3 months from treatment start date, e) Disease-free survival by flow at 6 months from treatment start date, f) Overall survival by flow at 6 months from treatment start date All curves are censored at the time of transplant or last follow-up. All the curves are presented from the time of MRD assessment CR, complete remission; MRD, minimal residual disease
Figure 2
Figure 2. Outcomes by MRD status at CR, 3 and 6 months from treatment
a) Disease-free survival by flow at CR, b) Overall survival by flow at CR, c) Disease-free survival by flow at 3 months from treatment start date, d) Overall survival by flow at 3 months from treatment start date, e) Disease-free survival by flow at 6 months from treatment start date, f) Overall survival by flow at 6 months from treatment start date All curves are censored at the time of transplant or last follow-up. All the curves are presented from the time of MRD assessment CR, complete remission; MRD, minimal residual disease
Figure 2
Figure 2. Outcomes by MRD status at CR, 3 and 6 months from treatment
a) Disease-free survival by flow at CR, b) Overall survival by flow at CR, c) Disease-free survival by flow at 3 months from treatment start date, d) Overall survival by flow at 3 months from treatment start date, e) Disease-free survival by flow at 6 months from treatment start date, f) Overall survival by flow at 6 months from treatment start date All curves are censored at the time of transplant or last follow-up. All the curves are presented from the time of MRD assessment CR, complete remission; MRD, minimal residual disease
Figure 2
Figure 2. Outcomes by MRD status at CR, 3 and 6 months from treatment
a) Disease-free survival by flow at CR, b) Overall survival by flow at CR, c) Disease-free survival by flow at 3 months from treatment start date, d) Overall survival by flow at 3 months from treatment start date, e) Disease-free survival by flow at 6 months from treatment start date, f) Overall survival by flow at 6 months from treatment start date All curves are censored at the time of transplant or last follow-up. All the curves are presented from the time of MRD assessment CR, complete remission; MRD, minimal residual disease
Figure 2
Figure 2. Outcomes by MRD status at CR, 3 and 6 months from treatment
a) Disease-free survival by flow at CR, b) Overall survival by flow at CR, c) Disease-free survival by flow at 3 months from treatment start date, d) Overall survival by flow at 3 months from treatment start date, e) Disease-free survival by flow at 6 months from treatment start date, f) Overall survival by flow at 6 months from treatment start date All curves are censored at the time of transplant or last follow-up. All the curves are presented from the time of MRD assessment CR, complete remission; MRD, minimal residual disease
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