Clinical outcomes of early WT1 mRNA reduction after remission induction in newly diagnosed acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation

Takafumi Tsushima; Chiharu Kimeda; Natsumi Yoda; Kosuke Matsuo; Kazusuke Tanaka; Yasuhito Hatanaka; Rena Matsumoto; Sonoko Shimoji; Yoshikazu Utsu; Shin-Ichi Masuda; Nobuyuki Aotsuka

doi:10.1016/j.jtct.2024.12.007

Clinical outcomes of early WT1 mRNA reduction after remission induction in newly diagnosed acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation

Transplant Cell Ther. 2024 Dec 16:S2666-6367(24)00807-8. doi: 10.1016/j.jtct.2024.12.007. Online ahead of print.

Affiliations

¹ Department of Hematology and Oncology, Japanese Red Cross Narita Hospital, Narita, Japan. Electronic address: emperor.penguin.is.1arge@gmail.com.
² Department of Hematology and Oncology, Japanese Red Cross Narita Hospital, Narita, Japan.

PMID: 39694194
DOI: 10.1016/j.jtct.2024.12.007

Abstract

Background: Wilms' Tumor (WT1) mRNA is a non-specific marker of measurable residual disease in acute myeloid leukemia (AML). Few studies have focused on the prognostic value of WT1 mRNA after initial remission induction of patients with AML who have received transplant treatments.

Objective: Thus, we retrospectively analyzed the clinical features and prognostic impact of WT1 mRNA reduction in patients with AML after initial remission induction at our hospital. We classified the reduction in WT1 mRNA levels using logarithmic stratification, with particular focus on the prognostic impact of a 3-log reduction after initial remission induction.

Study design: This single-center, retrospective, observational study included 71 consecutive patients with AML who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between April 2013 and June 2023 and had WT1 mRNA quantified.

Results: Patients were grouped based on whether a 3-log reduction was observed during follow-up (N=30) or not (N=41). Among patients who did not achieve a 3-log reduction, European Leukemia Net (ELN) 2022 adverse risk was more common, and fewer patients showed complete hematological responses at transplantation. Patients who reached a 3-log reduction in WT1 mRNA after the initial remission induction had significantly longer overall survival (OS) and progression-free survival (PFS) and a lower relapse rate than patients who had not reached a 3-log reduction (2-year OS: 79.7% vs. 27.5%, 2-year PFS: 83.1% vs. 11.7% and 2-year cumulative relapse rate: 5.9% vs. 81.2%). In multivariate analysis, a 3-log reduction in WT1 mRNA after initial remission induction and ELN 2022 adverse risk by genetics were significantly associated with OS and PFS.

Conclusion: We identified that patients with AML undergoing HSCT with an early and deep 3-log reduction in WT1 mRNA after initial remission induction were associated with low relapse rates and better long-term prognosis. Our data highlight the importance of WT1 mRNA reduction after initial remission induction.

Keywords: AML undergoing allo-HSCT; early reduced WT1 mRNA after remission induction.