Early Detection of WT1 Measurable Residual Disease Identifies High-Risk Patients Independently of Transplantation in AML.

WT1 overexpression is frequently identified in acute myeloid leukemia (AML) and has been reported as a potential marker for measurable residual disease (MRD) monitoring. Here, we evaluated the value of post-induction WT1 MRD level as a prognostic factor, as well as the interaction between post-induction WT1 MRD response and the effect of allogeneic stem cell transplantation (allo-SCT) in first complete remission (CR). In the ALFA-0702 trial, AML patients aged 18 to 59 years had a prospective quantification of WT1 MRD. Occurrence of a WT1 MRD ratio >2.5% in bone marrow or >0.5% in peripheral blood was defined as MRDhigh, while ratio under these thresholds was defined as MRDlow. The prognostic value of MRD after induction chemotherapy was assessed in 314 patients in first CR by comparing the risk of relapse, the relapse-free survival (RFS) and the overall survival (OS). Interaction between MRD response and allo-SCT effect was evaluated in patients by comparing the influence of allo-SCT on the outcomes of patients with MRDhigh and MRDlow. We showed that MRDhigh patients after induction had a higher risk of relapse and a shorter RFS and OS. MRD response remained of strong prognostic value in the subset of 225 patients with intermediate/unfavorable-risk AML, eligible for allo-SCT, since MRDhigh patients had a significantly higher risk of relapse resulting in worse RFS and OS. Effect of allo-SCT was higher in MRDlow patients than in MRDhigh patients but not statistically different. Early WT1 MRD response highlight a population of high-risk patients in need of additional therapies.