Abstract:

Objective To investigate the clinical characteristics, treatment strategies, and prognosis of pediatric acute myeloid leukemia (AML) with coexisting NUP98-NSD1 rearrangement and FLT3-ITD mutation. Methods A retrospective analysis was performed on two pediatric AML cases with NUP98-NSD1 rearrangement and FLT3-ITD mutation admitted to the Department of Pediatric Hematology, the Affiliated Hospital of Qingdao University. In addition, domestic and international literature was systematically searched, yielding 52 pediatric cases and 26 adult cases. Baseline characteristics, treatment responses, and prognosis were compared between the two groups. Results In the two cases from our center, the white blood cell count at diagnosis was >150.00×10⁹/L in both patients. Neither achieved complete remission (CR) after initial induction chemotherapy. CR was achieved after switching to second-line regimens (fludarabine+cytarabine+G-CSF [FLAG]/cladribine+cytarabine+homoharringtonine+G-CSF, [CHAG]), and CR was maintained after FLT3 inhibitor therapy combined with transplantation. The literature review showed no significant differences between the pediatric and adult groups in sex (P=0.090), +8/9q13/q32 karyotype (P=0.983), WT1 mutation (P=0.705), initial CR rate (30.0% vs 31.3%, P=1.000), transplantation rate (P=0.139), relapse rate (60.0% vs 64.3%, P=0.781), or mortality rate (57.1% vs 68.0%, P=0.394). However, the pediatric group had a significantly higher white blood cell count at diagnosis than the adult group (P=0.003), and the proportion of patients with a white blood cell count ≥150×10⁹/L at diagnosis was also significantly higher in the pediatric group than in the adult group (62.5% vs 16.7%, P=0.003). In contrast, the adult group had a significantly higher proportion of M4/M5 subtypes than the pediatric group (83.3% vs 51.1%, P=0.017). In the pediatric group, the initial remission rate was only 30.0%, the relapse rate reached 60.0%, and the mortality rate was 57.1%. Conclusion Pediatric AML with NUP98-NSD1 rearrangement and FLT3-ITD mutation often presents with marked leukocytosis at diagnosis, shows poor response to conventional induction chemotherapy, and is associated with high relapse and mortality rates, indicating a high-risk subtype. Although pediatric and adult patients are similar in most clinical and prognostic features, children are more prone to extreme leukocytosis, whereas adults more commonly present with M4/M5 subtypes. For both groups, an aggressive treatment strategy involving second-line therapy as a bridge to transplantation and targeted therapy is warranted.

Key words: leukemia, myeloid, children, NUP98-NSD1, FLT3-ITD, targeted therapy