GIMEMA AML1310 trial of risk-adapted, MRD-directed therapy for young adults with newly diagnosed acute myeloid leukemia.

We designed a trial in which post-remission therapy of young patients with de novo AML was decided combining cytogenetics/genetics and postconsolidation levels of minimal residual disease (MRD). After induction and consolidation, favorable-risk patients (FR) were to receive autologous stem cell transplant (AuSCT) and poor-risk patients (PR) allogeneic stem cell transplant (ASCT). Intermediate-risk patients (IR) were to receive AuSCT or ASCT depending on the post-consolidation levels of MRD. ASCT was to be delivered whatever the source of stem cells. Three hundred-61/500 patients (72%) achieved a CR, 342/361 completed the consolidation phase and were treatment allocated: 165 (48%) to ASCT (122 PR, 43 IR MRD-positive) plus 23 rescued after salvage therapy, for a total of 188 candidates; 150 (44%) to AuSCT (115 FR, 35 IR MRDnegative) plus 27 IR patients (8%) with no leukemia-associated phenotype, for a total of 177 candidates. Overall, 110/177 (62%) and 130/188 (71%) AuSCT or ASCT candidates received it, respectively. Two-year overall (OS) and disease-free survival (DFS) of the whole series was 56% and 54%, respectively. Two-year OS and DFS were 74% and 61% in the FR category, 42% and 45% in the PR category, 79% and 61% in the IR MRD-negative category, 70% and 67% in the IR MRD-positive category. In conclusion, AuSCT may still have a role in FR and IR MRDnegative categories. In the IR MRD-positive category, ASCT prolongs OS and DFS to equal those of the FR category. Using all the available sources of stem cells, ASCT was delivered to 71% of the candidates.