P545: characteristics and outcome of patients with acute myeloid leukemia and trisomy 19

Background: Trisomy 19 is a recurrent but rare cytogenetic abnormality reported in patients with acute myeloid leukemia (AML). The prognostic significance of this abnormality in AML patients is not clear. Prognosis of AML patients with trisomy 19 seems to be poor as compared to that of patients with intermediate-risk cytogenetics. Allogeneic hematopoietic stem cell transplantation (allo-HCT) may improve survival if applied early in first complete remission (CR). Aims: To characterize AML patients with trisomy 19 and compare outcomes according to different treatment strategies. Methods: We retrospectively studied 97 AML patients with trisomy 19 (median age at diagnosis, 57 years; range, 17-83 years) treated between 2001 and 2019 within 2 study groups (SAL & PETHEMA). Standard statistical methods were applied. Results: Median white blood cell count at diagnosis was 6.7/nl (range, 0.1-151/nl) and platelets 48.5/nl (range, 4-307/nl). Type of AML was de novo in 66 (68%), secondary after myelodysplastic syndrome/ myeloproliferative neoplasm in 16 (16%), and therapy-related in 9 (9%) patients (missing, n=6; 6%). Thirty-five (36%) patients were female. Cytogenetic analysis revealed trisomy 19 as the sole abnormality in 10 (12.5%), additional abnormalities in a non-complex karyotype in 8 (8%) and a complex karyotype in 79 (81.5%) patients. Most frequent additional cytogenetic abnormality was trisomy 8 (n=46); in 17 patients karyotypes were characterized by trisomies only. A total of 65 patients (67%) had NPM1 and FLT3-ITD mutation testing. Of those, only 3 (5%) and 1 (2%) harbored NPM1 and FLT3-ITD mutations, respectively. Only 4 (8%) of 51 patients were CEBPA mutated. Ninety-two patients (95%) were treated intensively and 4 (4%) received non-intensive therapy (missing, n=1, 1%). In intensively treated patients early death rate was 10% (n=9); CR was achieved in 52% (n=48) and 35% (n=35) patients were refractory. Factors associated with response to intensive induction therapy were trisomy 19 as sole abnormality or within a karyotype characterized by trisomies only (OR, 5.64; 95%-CI, 1.71-18.63; P=0.005) and age at diagnosis (10 years difference OR, 0.57; 95%-CI, 0.40-0.80; P=0.001). One of 4 patients treated non-intensively achieved a CR. An allo-HCT was performed in 34 (35%) patients, of whom 19 patients were transplanted in first CR after induction therapy. Type of donor was matched-related in 12 and matched-unrelated in 22 patients. Median follow-up of the whole cohort was 6.4 years (95%-CI, 2.91-8.97 years). Five-year overall (OS) and relapse-free survival rates were 20% (95%-CI, 13-31%) and 26% (95%-CI, 16-43%). OS rates were significantly higher in intensively treated patients with trisomy 19 as sole abnormality or within a karyotype characterized by trisomies only (P=0.05). An Andersen-Gill model including allo-HCT as a time dependent covariable on OS revealed as significant parameters trisomy 19 as sole abnormality or within a karyotype characterized by trisomies only (HR, 0.47; 95%-CI, 0.25-0.89; P=0.021) and age at diagnosis (10 years difference; HR, 1.29; 95%-CI, 1.10-1.52; P=0.002), whereas allo-HCT had no beneficial impact (HR, 1.45; 95%-CI, 0.81-2.59; P=0.21). Summary/Conclusion: Patients with trisomy 19 are very heterogeneous in particular with respect to cytogenetic and molecular abnormalities. In our cohort, patients with trisomy 19 as sole abnormality or within a karyotype characterized by trisomies only had a high CR rate and better clinical outcome. In the cohort of intensively treated patients, allo-HCT did not improve OS.