NUP98 Rearrangement Dynamics Predict Outcomes in Adult Patients With Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: A Multicenter Real-World Study.

BACKGROUND

Acute myeloid leukemia with NUP98 rearrangements (NUP98r) is associated with poor prognosis, and while allo-HSCT remains the primary curative approach, its efficacy in NUP98r patients is still uncertain. The prognostic impact of NUP98 fusion partners, accompanying genetic alterations, and NUP98r dynamics is unclear.

METHODS

We retrospectively analyzed 56 adult patients with NUP98r AML undergoing allo-HSCT across multiple centers. Primary outcomes included overall survival (OS), disease-free survival (DFS), and cumulative incidence of relapse (CIR).

RESULTS

The most common NUP98r were NUP98::HOXA9 and NUP98::NSD1. With a median follow-up of 755 days, the 2-year CIR, DFS, and OS rates were 28.4%, 69.8%, and 73.0%. Pre-transplant NUP98r status demonstrated no significant association with outcomes in complete remission patients, while nonremission status correlated with higher CIR and reduced survival. NUP98r positivity at 1 month post-HSCT predicted higher 2-year CIR (60.0% versus 21.5%, P = .013), reduced DFS (40.0% versus 78.5%, P = .008) and OS (40.0% versus 84.5%, P = .003). Outcomes worsened at 3 and 6 months, with 100% CIR in the NUP98r positive at 6 months. Multivariable analysis confirmed 1-month post-HSCT NUP98r positivity as an independent predictor of relapse and mortality, whereas pre-transplant NUP98r status lacked prognostic significance.

CONCLUSIONS

Patients with detectable NUP98r post-HSCT showed higher relapse risk and mortality, indicating the necessity for early molecular surveillance and early intervention trials in this high-risk subgroup.