White blood cell count as a powerful prognostic marker and treatment guide in paediatric acute myeloid leukaemia with NUP98 rearrangement.

NUP98-rearranged paediatric acute myeloid leukaemia (NUP98-r pAML) has an extremely poor prognosis, and the impact of clinical parameters and therapeutic schemes on its outcomes remains unclear. We conducted a retrospective study of the largest pAML cohort (1779 patients) and found that NUP98-r pAML has the worst prognosis among all subtypes. Furthermore, we identified white blood cell (WBC) count as the sole predictor of overall survival (OS) in NUP98-r pAML patients and validated its adverse prognostic impact in both external paediatric and adult cohorts. NUP98-r pAML patients were categorized into low-risk (WBC count ≤150 × 10⁹/L) and high-risk (WBC count >150 × 10⁹/L) groups based on WBC levels. Haematopoietic stem cell transplantation (HSCT) significantly improved OS and reduced the cumulative incidence of relapse (CIR) in the high-risk group but not in the low-risk group. Bortezomib significantly increased OS in NUP98::NSD1 patients within the low-risk group, and the combination of bortezomib and HSCT significantly enhanced OS in the entire NUP98-r pAML cohort. CD33 antibody (Gemtuzumab ozogamicin, GO) is not recommended for the entire NUP98-r pAML patients. In summary, WBC count is a pivotal marker for risk stratification and treatment decision-making in NUP98-r pAML patients.