TY - JOUR
T1 - Core binding factor acute myeloid leukemia: The impact of age, leukocyte count, molecular findings and minimal residual disease
AU - Hoyos, Montserrat
AU - Nomdedeu, Josep F.
AU - Esteve, Jordi
AU - Duarte, Rafael
AU - Ribera, Josep M.
AU - Llorente, Andreu
AU - Escoda, Lourdes
AU - Bueno, Javier
AU - Tormo, Mar
AU - Gallardo, David
AU - de Llano, Maria Paz Queipo
AU - Martí, Josep M.
AU - Aventín, Anna
AU - Mangues, Ramón
AU - Brunet, Salut
AU - Sierra, Jorge
PY - 2013/9/1
Y1 - 2013/9/1
N2 - Purpose: Most patients with acute myeloid leukemia (AML) and genetic rearrangements involving the core binding factor (CBF) have favorable prognosis. In contrast, a minority of them still have a high risk of leukemia recurrence. This study investigated the adverse features of CBF AML that could justify investigational therapeutic approaches. Patients and methods: One hundred and fifty patients (median age 42 yr, range 16-69) with CBF AML (RUNX1-RUNX1T1 n = 74; CBFB-MYH11 n = 76) were prospectively enrolled into two consecutive CETLAM protocols at 19 Spanish institutions. Main clinic and biologic parameters were analyzed in the whole series. In non-selected cases with available DNA samples, the impact of molecular characterization and minimal residual disease (MRD) was also studied. Results: Overall, complete remission (CR) rate was 89% (94% in ≤50 yr old and 72% in >50 yr, P = 0.002). At 5 yr, cumulative incidence of relapse (CIR) was 26 ± 1%, disease-free survival (DFS) 62 ± 6%, and overall survival (OS) 66 ± 4%. In multivariate analyses, leukocyte count above 20 × 10 9 /L, BAALC over-expression, and high copy numbers of RUNX1-RUNXT1 or CBFB-MYH11 after induction chemotherapy (CT) led to increased relapse rate. Regarding OS, age >50 yr, leukocyte count above 20 × 10 9 /L, and increased MN1 expression were adverse features. Conclusion: Age, leukocyte counts, BAALC, and MN1 gene expressions as well as high copy numbers of RUNX1-RUNXT1 or CBFB-MYH11 after induction chemotherapy are useful tools to predict the outcome and should be considered for risk-adapted therapy. 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
AB - Purpose: Most patients with acute myeloid leukemia (AML) and genetic rearrangements involving the core binding factor (CBF) have favorable prognosis. In contrast, a minority of them still have a high risk of leukemia recurrence. This study investigated the adverse features of CBF AML that could justify investigational therapeutic approaches. Patients and methods: One hundred and fifty patients (median age 42 yr, range 16-69) with CBF AML (RUNX1-RUNX1T1 n = 74; CBFB-MYH11 n = 76) were prospectively enrolled into two consecutive CETLAM protocols at 19 Spanish institutions. Main clinic and biologic parameters were analyzed in the whole series. In non-selected cases with available DNA samples, the impact of molecular characterization and minimal residual disease (MRD) was also studied. Results: Overall, complete remission (CR) rate was 89% (94% in ≤50 yr old and 72% in >50 yr, P = 0.002). At 5 yr, cumulative incidence of relapse (CIR) was 26 ± 1%, disease-free survival (DFS) 62 ± 6%, and overall survival (OS) 66 ± 4%. In multivariate analyses, leukocyte count above 20 × 10 9 /L, BAALC over-expression, and high copy numbers of RUNX1-RUNXT1 or CBFB-MYH11 after induction chemotherapy (CT) led to increased relapse rate. Regarding OS, age >50 yr, leukocyte count above 20 × 10 9 /L, and increased MN1 expression were adverse features. Conclusion: Age, leukocyte counts, BAALC, and MN1 gene expressions as well as high copy numbers of RUNX1-RUNXT1 or CBFB-MYH11 after induction chemotherapy are useful tools to predict the outcome and should be considered for risk-adapted therapy. 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
KW - Acute myeloid leukemia
KW - Biologic and molecular prognostic factors
KW - Core binding factors
U2 - 10.1111/ejh.12130
DO - 10.1111/ejh.12130
M3 - Article
VL - 91
SP - 209
EP - 218
IS - 3
ER -