Clinical characteristics and therapeutic determinants of RUNX1::RUNX1T1 differ from those of CBFB::MYH11 acute myeloid leukemia.

Core binding factor acute myeloid leukemia (CBF-AML) includes RUNX1::RUNX1T1 and CBFB::MYH11 AML. To investigate whether they should be regarded as distinct entities and treated separately, we retrospectively analyzed 536 patients with CBFAML aged 60 years or younger. For CBFB::MYH11 AML, no outcome differences were observed between standard-dose (SD) and intermediate-dose (ID) cytarabine induction, with 5-year overall survival (OS) and relapse-free survival (RFS) at 86.4% versus 85.3% (P=0.99) and 74.1% versus 68.4% (P=0.93), respectively. However, ID induction improved the outcomes of RUNX- 1::RUNX1T1 AML, with 5-year OS and RFS rates of 77.7% versus 60.3% (P<0.001) and 71.4% versus 54.1% (P<0.001), respectively. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) improved CBFB::MYH11 patients' RFS but not OS for both the entire CBFB::MYH11 cohort and patients with a measurable residual disease (MRD) <3-log reduction after two courses of chemotherapy. Allo-HSCT improved survival of RUNX1::RUNX1T1 patients with MRD <3-log reduction when receiving SD induction, with 5-year OS and RFS rates for transplantation versus non-transplantation of 71.9% versus 43.6% (P=0.023) and 72.9 % versus 35.0% (P=0.001), while conferring no additional benefits for those with ID regimen, with a 5-year OS and RFS of 35.6% versus 71.2% (P=0.73) and 37.4% versus 60.7% (P=0.71), respectively. Overall, our study suggests that RUNX1::RUNX1T1 and CBFB::MYH11 AML are different entities and should be treated with distinct strategies.