TY - JOUR
T1 - Minimal residual disease assessed by multi-parameter flow cytometry is highly prognostic in adult patients with acute lymphoblastic leukaemia
AU - Ravandi, Farhad
AU - Jorgensen, Jeffrey L.
AU - O'Brien, Susan M.
AU - Jabbour, Elias
AU - Thomas, Deborah A.
AU - Borthakur, Gautam
AU - Garris, Rebecca
AU - Huang, Xuelin
AU - Garcia-Manero, Guillermo
AU - Burger, Jan A.
AU - Ferrajoli, Alessandra
AU - Wierda, William
AU - Kadia, Tapan
AU - Jain, Nitin
AU - Wang, Sa A.
AU - Konoplev, Sergei
AU - Kebriaei, Partow
AU - Champlin, Richard E.
AU - Mccue, Deborah
AU - Estrov, Zeev
AU - Cortes, Jorge E.
AU - Kantarjian, Hagop M.
N1 - Publisher Copyright:
© 2016 John Wiley & Sons Ltd.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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.
AB - 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.
KW - Acute leukaemia
KW - Flow cytometry
KW - Minimal residual disease
UR - http://www.scopus.com/inward/record.url?scp=84955727108&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84955727108&partnerID=8YFLogxK
U2 - 10.1111/bjh.13834
DO - 10.1111/bjh.13834
M3 - Article
C2 - 26492205
AN - SCOPUS:84955727108
SN - 0007-1048
VL - 172
SP - 392
EP - 400
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 3
ER -