Differential Prognosis and Transplant Strategies in CBF-AML With RUNX1::RUNX1T1 Versus CBFβ::MYH11 Fusions.

Core binding factor acute myeloid leukemia (CBF-AML) is defined by t(8;21) or inv. (16), which give rise to the RUNX1::RUNX1T1 and CBFβ::MYH11 fusion genes, respectively. CBF-AML is a favorable-risk AML subtype, yet differences in mutation profiles, measurable residual disease (MRD) response, and relapse risk may warrant tailored treatment approaches. We reviewed adult AML patients treated at five transplant centers across China and identified 825 de novo CBF-AML cases, of which 779 met our eligibility criteria: 536 harbored the RUNX1::RUNX1T1 fusion and 243 the CBFβ::MYH11 fusion. The 3-year overall survival (OS) was 80.6% for RUNX1::RUNX1T1 and 90.2% for CBFβ::MYH11 cases (p = 0.011). Among patients with RUNX1::RUNX1T1, those achieving MRD negativity after two consolidation cycles (PC2) had significantly better OS than nonresponders (86.3% vs. 76.5%, p = 0.008); no difference was observed for CBFβ::MYH11 patients. For RUNX1::RUNX1T1 nonresponders, allogeneic hematopoietic cell transplantation (allo-HCT) in first complete remission (CR1) reduced relapse (CR1-HCT vs. non-CR1-HCT, 8.3% vs. 18.9%; p = 0.024) and improved OS (CR1-HCT vs. non-CR1-HCT vs. chemotherapy, 85.8% vs. 71.4% vs. 64.9%; p < 0.001). In CBFβ::MYH11 patients, deferring allo-HCT until second complete remission (CR2) was associated with comparable outcomes. In RUNX1::RUNX1T1 patients, older age, elevated initial white blood cell count, lower hemoglobin, lower initial fusion transcript load, and the presence of FLT3-ITD or KIT D816/D822 mutations were associated with an increased likelihood of PC2 nonresponse. Based on these variables, we developed a weighted scoring system with good discrimination to identify RUNX1::RUNX1T1 patients at high risk of PC2 nonresponse.