Combined prognostic impact of complex karyotype and KIT mutations refines risk stratification in t(8;21) acute...

Acute myeloid leukemia (AML) with t(8;21) is traditionally classified as favorable-risk; however, relapse occurs in 30%-50% of patients, indicating underlying heterogeneity. The prognostic impact and potential synergy of additional cytogenetic abnormalities (ACAs)-specifically complex karyotype (CK)-and KIT mutations remain poorly defined.

The authors conducted a retrospective cohort study of 243 adults with t(8;21) AML. CK was defined as the presence of two or more ACAs beyond t(8;21). Prognostic factors were evaluated using multivariable Cox proportional hazards models. An integrated risk stratification was developed based on CK and KIT mutation status. Minimal residual disease (MRD) was quantified via reverse transcriptase-polymerase chain reaction for the RUNX1::RUNX1T1 transcript.

CK was an independent predictor of inferior overall survival (OS), whereas KIT mutation predicted inferior disease-free survival (DFS) and event-free survival (EFS) (all p < .05). Based on this integrated stratification, patients were categorized into three groups: low-risk (CK-/KIT-, n = 128), intermediate-risk (CK+ or KIT+, n = 100), and high-risk (CK+/KIT+, n = 15). The 5-year OS rates were 72.8%, 58.3%, and 41.6%, respectively (p < .001). MRD positivity at the time of complete remission (CR) was associated with inferior relapse-free survival (RFS; p = .025) and showed a trend toward independent prognostic value (p = .068). Biologically, high-risk cases exhibited prominent KIT driver mutations and enrichment for stem cell maintenance pathways.

CK and KIT mutations jointly identify a high-risk subgroup within t(8;21) AML. This baseline genetic stratification provides a foundation for risk-adapted therapy, with MRD assessment at CR offering complementary prognostic information.