Impact of trisomy 19 on outcome according to genetic makeup in patients with acute myeloid leukemia

Abstract

We retrospectively studied 97 acute myeloid leukemia patients with trisomy 19 (median age at diagnosis 57 years; range, 17- 83 years) treated between 2001 and 2019 within two multicenter study groups. Trisomy 19 occurred alone in ten (10.5%) patients, with additional abnormalities being present in non-complex karyotypes in eight (8%) patients and in complex karyotypes in 79 (82%) patients. Altogether, karyotypes characterized by trisomies only were present in 27 (28%) patients. Data on response and outcome of intensively treated patients were available for 92 cases. The median follow-up was 6.4 years (95% confidence interval [95% CI]: 2.9-9.0 years). The complete remission (CR) rate after induction therapy was 52% (48 patients); the early death rate was 10% (n=9). Notably, patients with trisomy 19 as the sole abnormality had a CR rate of 89%. Allogeneic hematopoietic stem cell transplantation (allo-HCT) was performed in 34 (35%) patients (CR, n=19; active disease, n=15). Five-year relapse-free and overall survival rates were 26% (95% CI: 16-43%) and 20% (95% CI: 13-31%), respectively. Overall survival rates were significantly higher in patients with trisomy 19 as the sole abnormality or within karyotypes characterized by trisomies only (P=0.05). An Andersen-Gill model including allo-HCT as a time-dependent covariable on overall survival revealed that trisomy 19 as the sole abnormality or within karyotypes characterized by trisomies only was a favorable factor (hazard ratio [HR]=0.47; P=0.021); higher age at diagnosis had an adverse impact (10 years difference; HR=1.29; P=0.002), whereas allo-HCT did not have a beneficial impact (odds ratio=1.45; P=0.21). In our cohort, patients with trisomy 19 as the sole abnormality or within karyotypes characterized by trisomies only had a high CR rate and better clinical outcome.

Figure 1.

Cytogenetic abnormalities of 97 patients with trisomy 19 showing the categorization of cytogenetic abnormalities used for further analysis.

Figure 2.

Kaplan-Meier plot of overall survival in intensively treated patients according to cytogenetic abnormality. Tris: trisomy; abn: abnormalities.

Figure 3.

Simon Makuch plot of overall survival illustrating the impact of allogeneic hematopoietic stem cell transplantation evaluated as a time-dependent event. Allo-HCT: allogeneic hematopoietic stem cell transplantation.

Figure 4.

Overall survival afer allogeneic hematopoietic stem cell transplantation according to remission status. Allo-HCT: allogeneic hematopoietic stem cell transplantation. CR1: first complete remission.