Abstract

The aim was to determine the predictive value of karyotype in 132 patients ≥65 years in a series of 404 cases with de novo AML. 61 females and 71 males with median age 71 years (65–91). FAB subtype were: 14 (10.6%) M0, 21 M1, 37 M2, 14 (10.6%) M3, 16 M4 (only one M4Eo), 21 M5, 8 M6, 1 M7 (vs 4% M0, 25,7% M3 in <65 years p=0.004). The prognostic value of clinical, pathologic and cytogenetic factors was evaluated by Kaplan-Meier estimate and compared by log-rank, Breslow and Tarone test, for overall survival (OS) and continuous complete remission (CCR). Chi-square analysis for comparisons of remission rates were. The impact of prognostic factors was studied using Cox regression model. p≤0.01, M=median, m=months. Cytogenetic abnormalities were seen in 62.1% of cases including: 32 (24,2%) complex abnormalities, 18 of them with >5 aberrations (vs 7,3% in <65 years p<0.001), twelve (9,1%) t(15;17), 7 trisomy 8, 3 trisomy 21, 3 trisomy 11, 3 del(7q), 2 t(8;21), 2 t(9;22), 2 del(5q), two 3q21q26 rearrangement, one inv h (16), one 11q rearrangement, one monosomy 7 and 8 with other abnormalities. One normal karyotype had FLT3 and NPM1 mutations. Karyotype was classified by SWOG and MRC classification. 21.2% showed trilineage myelodysplasia (TMDS) (vs 10% in <65 years p=0.003). 80 patients received intensive chemotherapy (11 with AML-M3 also received ATRA). Only 53.8%(43/80) achieved CR(vs 78 % in <65 years p<0.001) and this was lowest in complex karyotype (13.3%).The 5-year OS and CCR probability was: 6,2% (M=2.9 m) and 13,8% (M=1.5 m).The longest OS was for t(15;17) with 41,7% surviving at 5 years (M=10.0 m); normal karyotypes survive 2,28% and other abnormalities had very short survival (p<0.0001). Patients with complex karyotypes survive 0% at 17 months and all had relapsed at 5,3. Probability of relapse in t (15;17) was 51.31 % at 5 years (M 12,30), and this was higher in normal karyotype (93,4%), trisomy 8 (100%) and other abnormalities (100%) (p=0.0008). A longer OS was seen in patients with leucocytes ≤ 10×109/L (p=0.0006), subtype M3 (p=0.009)/t(15;17) (p<0.0001) who received ATRA (p=0.0001) and without TMDS (p=0.0043). FAB subtypes distinct of M3 (p=0.0046), age adapted chemotherapy treatment (p=0.0004) and complex karyotypes (p=0.0007) were unfavourable prognostic factors for CCR. The survival of cytogenetic groups according SWOG and MCR was significantly different (p=0.0005, p =0.0021 for OS; p<0.0001, p=0.0001 for CCR). Multivariate analysis showed that karyotype, TMDS and leucocytes are independent factor for OS. The higher risk of dead is for unfavourable (OR 2.94 p=0,008) and unknown (OR 2,52 p=0,03) cytogenetic SWOG groups. Only unfavourable SWOG karyotypes and chemotherapy without ATRA are independent factor for relapse risk. The elderly novo AML has a similar clinical-biological profile that the secondary AML, because of high frequency in undifferentiated subtypes, frequent TMDS, high percentage of complex abnormalities and poor CR, CCR and OS. This matter suggest that their aetiology is probably a lengthy exposure to environmental toxins. That’s the reason because it’s essential the cytogenetic study to decide induction chemotherapy or palliative support. Elderly patients with de novo AML which shown unfavourable SWOG abnormalities, failure to achieve CR, relapse promptly and have short survival. In this age group, today, only therapy designed to target specific molecular rearrangements has good prognostic.

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