Impact of BCOR/BCORL1 mutation on outcomes of allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia patients.

Abstract

BCOR alteration is a well-established adverse-risk marker for acute myeloid leukemia (AML) in 2022 ELN risk stratification. However, outcomes of BCOR- or BCORL1-mutated AML after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are as yet poorly defined. In an 877-patient consecutive AML transplantation cohort, we found 83 (9.5%) patients with BCOR or BCORL1 mutation (BCOR/BCORL1^mut). We retrospectively evaluated the clinical characteristics and transplant outcomes of BCOR/BCORL1^mut patients and compared them with 276 patients with normal karyotype (BCOR/BCORL1^wt). Frameshift mutation was the predominant alteration of BCOR (n = 22, 39.3%), and the majority of BCORL1 was missense mutation (n = 25, 65.8%). The most common co-mutated gene of BCOR/BCORL1^mut was DNMT3A (n = 23, 27.7%). BCOR/BCORL1^mut was also associated with lower WBC counts at diagnosis (P = 0.003), shorter interval from diagnosis to transplantation (P = 0.037), and fewer achieved minimal residual disease negativity pre-transplantation (P < 0.001), compared to BCOR/BCORL1^wt. Three-year OS, DFS and CIR of BCOR/BCORL1^wt and BCOR/BCORL1^mut groups were 75.2% (95% CI, 70.0-80.8%) vs. 76.0% (95% CI, 66.0-87.5%) (HR, 0.92; 95% CI, 0.54-1.57; P = 0.77), 74.5% (95% CI, 69.4-80.1%) vs. 67.7% (95%CI, 57.0-80.4%) (HR, 1.20; 95% CI, 0.75-1.91; P = 0.46), and 12.6% (95% CI, 8.9-17.0%) vs. 24.0% (95% CI, 14.1-35.4%) (HR, 1.85; 95% CI, 1.04-3.3; P = 0.03), respectively. We also investigated the impact of the type and location of BCOR/BCORL1^mut on transplant outcomes, but no significant effect was observed. Our findings suggest that BCOR/BCORL1^mut is associated with relapse after allo-HSCT, despite no observed difference in OS, and that allo-HSCT could help to overcome the impact of BCOR/BCORL1^mut characteristics on outcomes.