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 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.
Departments of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Farhad
F
Ravandi
Departments of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jeffrey L
JL
Jorgensen
Departments of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Susan M
SM
O'Brien
Departments of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Elias
E
Jabbour
Departments of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Deborah A
DA
Thomas
Departments of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Gautam
G
Borthakur
Departments of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Rebecca
R
Garris
Departments of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Xuelin
X
Huang
Departments of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Guillermo
G
Garcia-Manero
Departments of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jan A
JA
Burger
Departments of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Alessandra
A
Ferrajoli
Departments of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
William
W
Wierda
Departments of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Tapan
T
Kadia
Departments of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nitin
N
Jain
Departments of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sa A
SA
Wang
Departments of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sergei
S
Konoplev
Departments of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Partow
P
Kebriaei
Departments of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Richard E
RE
Champlin
Departments of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Deborah
D
McCue
Departments of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Zeev
Z
Estrov
Departments of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jorge E
JE
Cortes
Departments of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Hagop M
HM
Kantarjian
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D016896:Treatment Outcome; D055815:Young Adult
acute leukaemia; flow cytometry; minimal residual disease