Aim. To address the heterogeneity of CBF AML patients- t(8;21)(q22;q22)/RUNX1-RUNX1T1 and inv(16)(p13q22)/t(16;16)(p13q22)/CBFB-MYH11- by assessing their char- acteristics at diagnosis and their response to therapy. Methods. we ret- rospectively studied 132 patients (t(8;21) n=58; inv(16)/t(16;16) n=74) treated with curative intent in 9 Hematology Centers between 1987 and 2012. Median follow-up was 66 months(10-294). Cytogenetic data at diagnosis were available for all patients, while only 39 had KIT(29.5%), 63 FLT3(47.7%) and 54 NPM1 assessment(40.9%). Patients were treat- ed with regimens either based on DA37 and similar (n=102) or first-line Fludarabine-containing regimens (n=30). All patients achieving complete remission (CR) after induction were consolidated with 1 (n=18), 2 (n=49) or >3 (n=50) cycles with HiDAC. 29 patients underwent ASCT, and 15 first-line allogeneic HSCT. Results. median age was 44 yrs (15-79). 5-year OS, DFS and EFS of the whole series was 62%, 58.9% and 53.5%, respectively. While achieving high CR rates after induction (86.2% vs 90.5%, P=NS), patients with t(8;21) experienced worse 5-yr OS (57.3% vs 67.7%, P=0.09), DFS (47.0 vs 67.5, P=0.015) and EFS (43.6% vs 60.8%, P=0.045) than patients with inv16/t(16;16), due to a trend to higher relapse (48% vs 32.8%, P=NS) and poorer response to salvage treament. Considering all patients, age >61 yrs, grade-4 thrombocytopenia, ele- vated LDH and D816 KIT mutation were predictive for poorer OS, while the presence of extramedullary disease/granulocytic sarchoma, and D816 KIT mutation were prognostically relevant only for t(8;21) patients; con- versely, age>61, leukocytosis and grade-4 thrombocytopenia were pre- dictive only for inv16/t(16:16) patients. Noteworthy, D816 KIT mutation did not predict prognosis in inv(16)/t(16;16) patients. Additional trisomy 22 (n=7), trisomy 8 (n=5) and chromosome 7 alterations (n=6) were asso- ciated with a trend to better survival. Neither the presence of FLT3 muta- tions (ITD/TKD) nor the presence of NPM1 mutations affected progno- sis. The use of first-line Fludarabine did not yield clear advantages, while the achievement of complete remission after induction had maximal impact on OS (HR 4.82; 95%CI: 2.29-10.16, p<0.001). We observed a clear survival benefit in a small selected series consolidated by first-line autologous (n=29) or allogenic HSCT (n=15, P=0.022) after HiDAC. Con- clusions:t(8;21) and inv(16)/t(16;16) CBF AML should be considered as two distinct entities.
SIMILAR BUT NOT THE SAME: CHROMOSOMAL ABNORMALITIES T(8;21)(Q22;Q22) AND INV(16)(P13;Q22)/T(16;16)(P13;Q22) IDENTIFY SUBTYPES OF CORE BINDING FACTOR ACUTE MYELOID LEUKEMIA CHARACTERIZED BY DIFFERENT SURVIVAL AND PROGNOS- TIC FACTORS
MOSNA, Federico;TECCHIO, Cristina;
2013-01-01
Abstract
Aim. To address the heterogeneity of CBF AML patients- t(8;21)(q22;q22)/RUNX1-RUNX1T1 and inv(16)(p13q22)/t(16;16)(p13q22)/CBFB-MYH11- by assessing their char- acteristics at diagnosis and their response to therapy. Methods. we ret- rospectively studied 132 patients (t(8;21) n=58; inv(16)/t(16;16) n=74) treated with curative intent in 9 Hematology Centers between 1987 and 2012. Median follow-up was 66 months(10-294). Cytogenetic data at diagnosis were available for all patients, while only 39 had KIT(29.5%), 63 FLT3(47.7%) and 54 NPM1 assessment(40.9%). Patients were treat- ed with regimens either based on DA37 and similar (n=102) or first-line Fludarabine-containing regimens (n=30). All patients achieving complete remission (CR) after induction were consolidated with 1 (n=18), 2 (n=49) or >3 (n=50) cycles with HiDAC. 29 patients underwent ASCT, and 15 first-line allogeneic HSCT. Results. median age was 44 yrs (15-79). 5-year OS, DFS and EFS of the whole series was 62%, 58.9% and 53.5%, respectively. While achieving high CR rates after induction (86.2% vs 90.5%, P=NS), patients with t(8;21) experienced worse 5-yr OS (57.3% vs 67.7%, P=0.09), DFS (47.0 vs 67.5, P=0.015) and EFS (43.6% vs 60.8%, P=0.045) than patients with inv16/t(16;16), due to a trend to higher relapse (48% vs 32.8%, P=NS) and poorer response to salvage treament. Considering all patients, age >61 yrs, grade-4 thrombocytopenia, ele- vated LDH and D816 KIT mutation were predictive for poorer OS, while the presence of extramedullary disease/granulocytic sarchoma, and D816 KIT mutation were prognostically relevant only for t(8;21) patients; con- versely, age>61, leukocytosis and grade-4 thrombocytopenia were pre- dictive only for inv16/t(16:16) patients. Noteworthy, D816 KIT mutation did not predict prognosis in inv(16)/t(16;16) patients. Additional trisomy 22 (n=7), trisomy 8 (n=5) and chromosome 7 alterations (n=6) were asso- ciated with a trend to better survival. Neither the presence of FLT3 muta- tions (ITD/TKD) nor the presence of NPM1 mutations affected progno- sis. The use of first-line Fludarabine did not yield clear advantages, while the achievement of complete remission after induction had maximal impact on OS (HR 4.82; 95%CI: 2.29-10.16, p<0.001). We observed a clear survival benefit in a small selected series consolidated by first-line autologous (n=29) or allogenic HSCT (n=15, P=0.022) after HiDAC. Con- clusions:t(8;21) and inv(16)/t(16;16) CBF AML should be considered as two distinct entities.
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