Prediction of post-remission survival in acute myeloid leukaemia: a post-hoc analysis of the AML96 trial

Background The optimum post-remission treatment (PRT) in acute myeloid leukaemia (AML) is still a matter of debate. Consolidation treatments include chemo therapy with high-dose cytarabine, or allogeneic or autologous haemopoietic stem cell transplantation (HSCT). In a post-hoc analysis of the AML96 trial (NCT00180115), our aim was to differentiate groups of patients according to the treatments that would provide them optimum benefit. Methods In the multicentre AML96 trial, 586 patients (aged 15-60 years) with AML-excluding those with t(8;21)-who were in complete remission after double induction treatment were consolidated with allogeneic HSCT, autologous HSCT, or chemotherapy containing high-dose cytarabine in a priority-based and risk-adapted manner. We assessed the association between potentially prognostic variables and overall survival after complete remission by use of a stratified Cox regression analysis. With the significant variables of the resulting model, we developed a PRT score in 452 patients with a complete dataset. This score was then validated by use of data from 407 patients from the AML2003 trial (NCT00180102). Findings Age, percentage of CD34-positive blasts, FLT3-ITD mutant-to-wild-type ratio, cytogenetic risk, and de-novo or secondary AML were identified as independent prognostic factors, and included in the PRT score. The PRT score separated patients in AML96 into three groups: favourable (n=190; 3-year survival 68%, 95% CI 60-74), intermediate (n=198; 49%, 42-56), and unfavourable (n=64; 20%, 12-31). All pair-wise comparisons of two of three PRT score groups were significant in the log-rank test (p<0.0001). Similar results were noted when data from AML2003 were used: 3-year survival for the favourable group (n=265) was 69% (62-76), for the intermediate group (n=114) it was 61% (50-71), and for the unfavourable group (n=28) it was 46% (24-65). The overall comparison between the three risk groups resulted in significantly different survival probabilities (p=0.015). We also analysed response to treatment in AML96 in each of the PRT score groups. In the favourable group, patients given allogeneic HSCT (n=60) had higher survival probabilities (82%, 69-89) than did those given chemotherapy (n=56, 55%, 41-67; p=0.0012) or autologous HSCT (n=74, 66%, 54-76; p=0.044). In the intermediate PRT score group, patients given autologous HSCT (n=69) had the best survival probabilities (62%, 50-72) compared with those given chemotherapy (n=72, 41%, 30-52; p=0.0006) or allogeneic HSCT (n=57, 44%, 31-56; p=0.0045). Interpretation The PRT score groups could help physicians to tailor treatment for patients with AML and our results lend support to the use of autologous HSCT in patients aged 60 years or younger with an intermediate PRT score.