Summary NUP98 rearrangements define a high‐risk, genetically heterogeneous subtype of paediatric acute myeloid leukaemia (AML), yet comprehensive clinicogenetic and survival data remain limited. This retrospective, single‐centre study of 32 paediatric patients (2017–2025) found a median age of 8.7 years and predominance of the NUP98::NSD1 fusion (68.8%), frequently co‐mutated with FLT3 ‐ITD (50%) and WT1 (43.8%). Complete remission (CR) rates increased from 53.1% to 87.5% after first and second induction. With a median follow‐up of 41.7 months, the estimated 3‐year overall survival (OS), event‐free survival (EFS) and cumulative incidence of relapse (CIR) were 81.2% (95% confidence interval CI, 65.9%–96.5%), 62.8% (95% CI, 43.8%–81.8%) and 28.1% (95% CI, 12.9%–45.6%), respectively; corresponding rates among the 29 transplanted patients were 79.8% (95% CI, 63.5%–96.1%), 68.7% (95% CI, 50.3%–87.1%) and 26.0% (95% CI, 11.1%–43.9%) respectively. Exploratory multivariate analysis identified failure to achieve CR after induction 2 as a risk factor for OS, WT1 mutation for relapse in the entire cohort and pretransplant minimal residual disease (MRD) positivity for relapse in the transplant subgroup. This confirms that NUP98 ‐rearranged AML necessitates intensive therapy including transplant and highlights WT1 and pretransplant MRD as key prognostic markers for risk‐adapted strategies.
Zhang et al. (Tue,) studied this question.