Characteristics and prognosis of paediatric normal karyotype acute myeloid leukaemia: A NOPHO-DBH AML study

Normal karyotype acute myeloid leukaemia (NK-AML) in children is a heterogeneous subgroup with scarce data on characteristics and prognosis. We investigated NK-AML in a large paediatric AML cohort from four trials of the Nordic Society for Paediatric Haematology and Oncology-Dutch Belgian Hongkong (NOPHO-DBH) group. Among 1476 AML patients, we identified 316 NK-AML patients (21%). NK-AML was characterized by high frequencies of FLT3 internal tandem duplications (ITD, 33%), mutated NPM1 (28%), WT1 (25%) and CEBPA (21%). Five-year event-free survival (EFS) and overall survival (OS) in NK-AML were 52% (95% confidence interval [CI]: 46–58) and 70% (CI: 65–75) respectively. Restricted to NPM1^wt cases only (n = 959), NK-AML was associated with unfavourable outcome (relative risk [RR] of EFS = 0.80, p = 0.014; RR of OS = 0.87, p = 0.022). NK-AML with mutated NPM1 had excellent EFS (79%, CI: 66–88) and OS (97%, CI: 88–99), which was not influenced by concomitant FLT3-ITD. In multivariable analysis, mutated NPM1 in NK-AML was associated with favourable EFS (hazard ratio [HR]: 0.24, CI: 0.13–0.43, p < 0.001) and OS (HR: 0.10, CI: 0.03–0.35, p < 0.001). FLT3-ITD was associated with inferior EFS (HR: 1.56, CI: 1.03–2.35, p = 0.035) and OS (HR: 1.91, CI: 1.11–3.31, p = 0.02). We conclude that prognosis in paediatric NK-AML is independently affected by NPM1 and FLT3-ITD status. Further molecular characterization of NK-AML is needed, especially for NPM1^wt NK-AML.