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

Summary 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 × 10 9 /L) and high‐risk (WBC count >150 × 10 9 /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.