CBFB::MYH11 MRD after the second chemotherapy cycle: a guide for allogeneic transplantation in favorable-risk AML

Although acute myeloid leukemia (AML) with CBFB::MYH11 rearrangement is classified as favorable-risk, approximately 40% of patients experience relapse. We evaluated the prognostic impact of CBFB::MYH11 transcript levels and the optimal timing of allogeneic hematopoietic cell transplantation (allo-HCT) at first complete remission (CR1). A total of 186 patients with CBFB::MYH11-rearranged AML treated with intensive induction chemotherapy were included. CBFB::MYH11 levels after cycles 2 and 3 were strongly correlated (P < 0.001). The post-cycle 2 CBFB::MYH11 transcript level emerged as the strongest prognostic marker for both disease-free survival (DFS) and overall survival (OS), outperforming assessments after cycles 1 or 3. CBFB::MYH11 ≥ 1% after cycle 2 was independently associated with inferior DFS (HR 3.84, P < 0.001) and OS (HR 3.98, P = 0.003). Among patients with post-cycle 2 CBFB::MYH11 ≥ 1.0%, the 3-year DFS and OS were both 91.7% in patients who received allo-HCT at CR1, compared with 47.8% and 72.9%, respectively, in the chemotherapy consolidation group. Multivariate analysis indicated that allo-HCT in CR1 improved 3-year DFS compared with chemotherapy consolidation (HR 0.24; P = 0.023). However, no significant improvement in OS was observed during follow-up. These findings suggest that post-cycle 2 CBFB::MYH11 level ≥1.0% identifies a high-risk subgroup that may benefit from allo-HCT in CR1.