WT1 Gene Expression in Peripheral Blood Before and After Allogeneic Stem Cell Transplantation is a Clinically Relevant Prognostic Marker in AML - A Single-center 14-year Experience
Abstract
We analyzed WT1 expression in peripheral blood before and after allogeneic hematopoietic stem cell transplantation (SCT) in a total of 147 patients with acute myeloid leukemia transplanted in complete remission. The results confirmed that WT1 status before allogeneic hematopoietic SCT is a strong prognostic factor for both overall survival and relapse risk and that WT1 is useful for minimal residual disease monitoring after allogeneic hematopoietic SCT and can serve as a guide to early intervention.
Background: This work summarizes our experience with WT1 monitoring before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients and Methods: The expression of WT1 gene was measured by realtime polymerase chain reaction in peripheral blood according to the European Leukemia Net recommendations.
Between May 2005 and August 2019, we analyzed 147 consecutive patients with acute myeloid leukemia with high WT1 expression at diagnosis, transplanted in first (CR1) or second (CR2) complete remission. Results: At the time of alto-HSCT, 107 patients had WT1-normal expression (WT1 <= 50 copies), and 40 patients had WT1-high expression.
The median follow-up was 21 months. The estimated 5-year overall survival and event-free survival was significantly better in the WT1-normal cohort (65% and 57% vs. 37% and 25%; P - .0003 and P < .0001, respectively) and 5-year cumulative incidence of relapse was significantly lower in the WT1-normal group (19% vs. 53%; P < .0001).
Five-year non-relapse mortality was not significantly different (20% and 23%). Multivariate analysis revealed WT1-high expression and acute graft-versus-host disease grade 3/4 as significantly negative prognostic factors for OS.
Overall, 49 patients developed WT1 molecular relapse in the post-transplant period; in 14 cases, the therapeutic intervention was done. In all but 1 relapsed patient where WT1 minimal residual disease (MRD) was monitored (38 patients), we detected WT1-high levels (sensitivity of 97%).
Conclusion: The results of the analysis confirmed our previous experience that WT1 status before alto-HSCT is a strong prognostic factor for both OS and relapse risk. In addition, we confirmed the usefulness of this marker for MRD monitoring after allo-HSCT.
The main advantage is the possibility of frequent MRD monitoring in peripheral blood and early bone marrow examination based on WT1-high expression. (C) 2020 Elsevier Inc. All rights reserved.