Usefulness of KIT mutant transcript levels for monitoring measurable residual disease in t (8;21) acute myeloid leukemia

Abstract In addition to RUNX1::RUNX1T1 transcript levels, measurable residual disease monitoring using KIT mutant (KIT mut ) DNA level is reportedly predictive of relapse in t (8; 21) acute myeloid leukemia (AML). However, the usefulness of KIT mut transcript levels remains unknown. A total of 202 bone marrow samples collected at diagnosis and during treatment from 52 t (8; 21) AML patients with KIT mut (D816V/H/Y or N822K) were tested for KIT mut transcript levels using digital polymerase chain reaction. The individual optimal cutoff values of KIT mut were identified by performing receiver operating characteristics curve analysis for relapse at each of the following time points: at diagnosis, after achieving complete remission (CR), and after Course 1 and 2 consolidations. The cutoff values were used to divide the patients into the KIT mut ‐high (KIT_H) group and the KIT mut ‐low (KIT_L) group. The KIT_H patients showed significantly lower relapse‐free survival (RFS) and overall survival (OS) rates than the KIT_L patients after Course 1 consolidation ( p = 0.0040 and 0.021, respectively) and Course 2 consolidation ( p = 0.018 and 0.011, respectively) but not at diagnosis and CR. The <3‐log reduction in the RUNX1::RUNX1T1 transcript levels after Course 2 consolidation was an independent adverse prognostic factor for RFS and OS. After Course 2 consolidation, the KIT_H patients with >3‐log reduction in the RUNX1::RUNX1T1 transcript levels (11/45; 24.4%) had similar RFS as that of patients with <3‐log reduction in the RUNX1::RUNX1T1 transcript levels. The combination of KIT mut and RUNX1::RUNX1T1 transcript levels after Course 2 consolidation may improve risk stratification in t (8; 21) AML patient with KIT mutation.