Work

Impact of Wilms Tumor (WT1) Mutation on Relapse and Overall Survival in Acute Myeloid Leukemia Patients Following Allogenic Stem Cell Transplantation

Year: 2024

Type: article

Abstract: Wilms tumor mutations (WT)-1 are associated with inferior survival in acute myeloid leukemia (AML); but not considered a high-risk genetic category in the European LeukemiaNet (ELN) guidelines. We compared post-allogeneic stem cell transplant (alloSCT) outcomes of WT1mut AML patients with a known poor prognostic category – TP53mut AML. We retrospectively reviewed patients (April 2016 -June 2023) who underwent alloSCT for WT1mut or TP53mut AML at Mayo Clinic Enterprise. Comparative analysis was performed with Chi Square test and Fisher's Exact test. Kaplan–Meier and log-rank tests were used to estimate overall survival (OS). Non-relapse mortality (NRM) and relapse incidence (RI) was calculated using competing risk analysis (R, v4.2.0). Of 53 AML patients, 18 had WT1mut and 35 had TP53mut. None had concurrent WT1mut and TP53mut. WT1mut AML patients were significantly younger (median age 36.5 vs 61.6 years, P<0.001), and had lower likelihood to be therapy-related (5.5 vs 28.6%, P=0.05), harbor complex (5.5 vs. 88.6%, P<0.001) or monosomal karyotype (0% vs 80%, P<0.001) compared to TP53mut AML. A higher proportion of WT1mut AML achieved morphologic and cytogenetic remission pre-alloSCT (88.8 vs 54.2%, P=0.011) compared to TP53mut AML (Table 1). The 2-year OS (38.7 vs 39.4%, P= 0.58, Figure1), NRM (28.9 vs.15.4%, P=0.46, Figure 2) and RI (37.3 vs 58.9%, P=0.19) were comparable between WT1mut and TP53mut AML. In a multivariable analysis that included age at diagnosis, complex and monosomal karyotype, pre-alloSCT disease status, mutation status (i.e., WT1mut vs TP53mut) was not independently associated with survival (Figure 3). Despite the younger age and diploid cytogenetics, WT1mut AML patients had comparable OS, RI and NRM to TP53mut AML. WT1mut should be considered high-risk feature in AML patients undergoing alloSCT. Approaches targeting WT1 are urgently needed to improve survival in this population.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2023.12.178