Core binding factor acute myeloid leukemia: the impact of age, leukocyte count, molecular findings, and minimal residual disease


Por: Hoyos, M, Nomdedeu, JF, Esteve, J, Duarte, R, Ribera, JM, Llorente, A, Escoda, L, Bueno, J, Tormo, M, Gallardo, D, de Llano, MPQ, Marti, JM, Aventin, A, Mangues, R, Brunet, S, Sierra, J

Publicada: 1 sep 2013
Resumen:
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 CBFAML that could justify investigational therapeutic approaches. Patients and methods One hundred and fifty patients (median age 42yr, range 16-69) with CBFAML (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 50yr old and 72% in >50yr, P=0.002). At 5yr, 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 20x10(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 >50yr, leukocyte count above 20x10(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.

Filiaciones:
Hoyos, M:
 Univ Autonoma Barcelona, Spanish Canc Network RTICC, Hosp Santa Creu & St Pau, Spanish CETLAM Grp,Inst Invest Biomed St Pau, E-08193 Barcelona, Spain

 Univ Barcelona, Barcelona, Spain

Nomdedeu, JF:
 Univ Autonoma Barcelona, Spanish Canc Network RTICC, Hosp Santa Creu & St Pau, Spanish CETLAM Grp,Inst Invest Biomed St Pau, E-08193 Barcelona, Spain

Esteve, J:
 Univ Autonoma Barcelona, Spanish Canc Network RTICC, Hosp Santa Creu & St Pau, Spanish CETLAM Grp,Inst Invest Biomed St Pau, E-08193 Barcelona, Spain

Duarte, R:
 Univ Autonoma Barcelona, Spanish Canc Network RTICC, Hosp Santa Creu & St Pau, Spanish CETLAM Grp,Inst Invest Biomed St Pau, E-08193 Barcelona, Spain

Ribera, JM:
 Univ Autonoma Barcelona, Spanish Canc Network RTICC, Hosp Santa Creu & St Pau, Spanish CETLAM Grp,Inst Invest Biomed St Pau, E-08193 Barcelona, Spain

Llorente, A:
 Univ Autonoma Barcelona, Spanish Canc Network RTICC, Hosp Santa Creu & St Pau, Spanish CETLAM Grp,Inst Invest Biomed St Pau, E-08193 Barcelona, Spain

Escoda, L:
 Univ Autonoma Barcelona, Spanish Canc Network RTICC, Hosp Santa Creu & St Pau, Spanish CETLAM Grp,Inst Invest Biomed St Pau, E-08193 Barcelona, Spain

Bueno, J:
 Univ Autonoma Barcelona, Spanish Canc Network RTICC, Hosp Santa Creu & St Pau, Spanish CETLAM Grp,Inst Invest Biomed St Pau, E-08193 Barcelona, Spain

Tormo, M:
 Univ Autonoma Barcelona, Spanish Canc Network RTICC, Hosp Santa Creu & St Pau, Spanish CETLAM Grp,Inst Invest Biomed St Pau, E-08193 Barcelona, Spain

Gallardo, D:
 Univ Autonoma Barcelona, Spanish Canc Network RTICC, Hosp Santa Creu & St Pau, Spanish CETLAM Grp,Inst Invest Biomed St Pau, E-08193 Barcelona, Spain

de Llano, MPQ:
 Univ Autonoma Barcelona, Spanish Canc Network RTICC, Hosp Santa Creu & St Pau, Spanish CETLAM Grp,Inst Invest Biomed St Pau, E-08193 Barcelona, Spain

Marti, JM:
 Univ Autonoma Barcelona, Spanish Canc Network RTICC, Hosp Santa Creu & St Pau, Spanish CETLAM Grp,Inst Invest Biomed St Pau, E-08193 Barcelona, Spain

Aventin, A:
 Univ Autonoma Barcelona, Spanish Canc Network RTICC, Hosp Santa Creu & St Pau, Spanish CETLAM Grp,Inst Invest Biomed St Pau, E-08193 Barcelona, Spain

Mangues, R:
 Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Barcelona, Spain

Brunet, S:
 Univ Autonoma Barcelona, Spanish Canc Network RTICC, Hosp Santa Creu & St Pau, Spanish CETLAM Grp,Inst Invest Biomed St Pau, E-08193 Barcelona, Spain

Sierra, J:
 Univ Autonoma Barcelona, Spanish Canc Network RTICC, Hosp Santa Creu & St Pau, Spanish CETLAM Grp,Inst Invest Biomed St Pau, E-08193 Barcelona, Spain

 Banc Sang & Teixits Catalunya, Barcelona, Spain
ISSN: 09024441





EUROPEAN JOURNAL OF HAEMATOLOGY
Editorial
WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, Dinamarca
Tipo de documento: Article
Volumen: 91 Número: 3
Páginas: 209-218
WOS Id: 000323048800004
ID de PubMed: 23646898

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