THE DIFFERENCES IN PROGNOSTIC OUTCOME BETWEEN AML1/ETO AND CBFb/MYH11 POSITIVE AML PATIENTS

Sborník

Background. CBF-AML is considered to be a good-risk subtype of AML. However, there might be differences within this subgroup according to the respective fusion gene as well as due to various secondary aberrations. The results published so far are quite inconsistent. Aims. To search for possible differences in clinical outcome between patients with AML1/ETO and CBFβ/MYH11 fusion genes. Patients and Methods. CBF-AML was diagnosed in 49 patients, their median age being 38.7 (18.5-70.6) years. The male/female ratio was 34/15, median follow-up was 38 months. RNA from 46 of them was available for searching of secondary aberrations. Minimal residual disease (MRD) was prospectively followed up in 39 patients.Presence of AML1/ETO and CBFβ/MYH11 was detected by RT-PCR; MRD was monitored using real time RT-PCR. Direct sequencing was used to identify patients carrying secondary alterations such as FLT3/ITD, FLT3 D835, C-KIT or K-RAS mutations. Results. 27 patients had AML1/ETO, 9/26 (34.6%) harboured secondary aberration (2 had FLT3/ITD, 2 FLT3 D835, 4 carried C-KIT and 1 K-RAS mutations). 22 patients were CBFβ/MYH11 positive, 13/20 (65.0%) had another molecular lesion (2 had FLT3/ITD, 5 FLT3/TKD, 7 C-KIT and 2 K-RAS mutations), 2 patients carried more than one of these changes. Secondary aberrations were more frequent among CBFβ/MYH11 patients (P=0.020).The initial median WBC count was 15.8 x 109/L (1.3-256.1 x 109/L) and it differed between the AML1/ETO and CBFβ/MYH11 cases (12.8 vs. 52.5 x 109/L; P=0.004). CBFβ/MYH11-positive patients harbouring any of secondary molecular aberrations had higher WBC (105.3 vs. 30.5 x 109/L; P=0.081).All but 3 patients (all of them having AML1/ETO) reached complete remission (CR). 12 of 20 (60.0%) patients carrying AML1/ETO achieved molecular remission (MR; defined as MRD negativity in at least two following bone marrow samples, with a minimal interval of 2 months), while only 7/16 (43.8%; P=0.166) CBFβ/MYH11-positive patients reached MR. Reaching MR was unfavourably influenced by the presence of any of the secondary aberrations monitored (P=0.023). Relapse free survival (RFS) was longer in cases reaching MR (P<0.0001) and there was no difference between AML1/ETO and CBFβ/MYH11 cases. Only 1/19 (5.3%) patients reaching MR relapsed, while 9 relapses among 15 patients (60.0%) without MR were observed (P<0.0001). Patients achieving MR had also significantly longer overall survival (OS; P=0.025).CBFβ/MYH11-positive patients more often relapsed than those with AML1/ETO fusion (63.6% vs. 20.8%; P=0.002) and their RFS was shorter (P=0.014). The incidence of relapse as well as RFS was influenced by the presence of the secondary aberration only within the CBFβ/MYH11-positive subgroup (P=0.055 and P=0.033, respectively), not in the AML1/ETO patients (P=0.300 for relapse rate and P=0.603 for RFS). Although OS was not affected by the particular fusion gene within the whole group (P=0.878), when patients not reaching CR were excluded, there was a trend to shorter post-remission survival in CBFβ/MYH11 cases (P=0.129). Conclusions. In our CBF-AML patient cohort, CBFβ/MYH11-positive cases had shorter RFS and higher incidence of relapse than those carrying AML1/ETO fusion. This might result from lower MR rate caused probably by higher incidence of the secondary molecular aberrations.

Haematologica, 2012; 97(s1):  273