Prognostic Impact of Sequential Measurable Residual Disease and KIT Variant Status in Pediatric Core-Binding Factor Acute Myeloid Leukemia: A Retrospective Multicenter Study of the Taiwan Pediatric Oncology Group.
In a retrospective multicenter cohort of 112 children with core-binding factor AML, sequential fusion-transcript MRD thresholds—particularly at the end of consolidation—and KIT D816 status were associated with survival and relapse outcomes.
Open original publication →What the AI sees
In a retrospective multicenter cohort of 112 children with core-binding factor AML, sequential fusion-transcript MRD thresholds—particularly at the end of consolidation—and KIT D816 status were associated with survival and relapse outcomes.
Research significance
The evidence supports sequential MRD plus KIT status as a prognostic stratification approach; it may, by inference, help identify children who could benefit from treatment intensification, de-escalation, or closer surveillance, but the record does not test any MRD-guided or KIT-directed therapeutic strategy.
Source abstract
BACKGROUND: Although measurable residual disease (MRD) is an established prognostic marker in pediatric acute myeloid leukemia (AML), its dynamic prognostic value during treatment and its integration with the KIT variant status in core-binding factor (CBF)-AML remain incompletely defined. We evaluated the prognostic impact of sequential MRD and KIT variants in pediatric CBF-AML. METHODS: We retrospectively analyzed 112 children with CBF-AML. We assessed MRD in bone marrow samples collected at diagnosis, the end of induction (EOI), the end of second consolidation (EO2C), and the end of consolidation (EOC) using quantitative reverse transcription PCR with TaqMan assays targeting two fusion transcripts. RESULTS: In RUNX1::RUNX1T1 AML, a ≥ 3-log reduction (LR) in MRD at EO2C or a ≥ 4-LR at EOC was associated with favorable outcomes, regardless of the MRD at EOI. Conversely, RUNX1::RUNX1T1 AML with an MRD of <4-LR and a normalized copy number of >500 at EOC was associated with extremely poor survival. CBFB::MYH11 AML with an MRD at EOI of ≥ 2-LR and an MRD of ≥ 4-LR at EOC was associated with better 5-yr overall survival and relapse-free survival (RFS), respectively. RUNX1::RUNX1T1 AML with a KIT D816 variant showed significantly lower 5-yr RFS (P =0.017). In patients with CBF-AML harboring a KIT variant, those who achieved MRD of ≥ 4-LR at EOC had significantly more favorable outcomes. CONCLUSIONS: Our findings highlight the importance of sequential MRD monitoring in pediatric patients with RUNX1::RUNX1T1 AML and show that integrating the KIT variant status with MRD assessment provides additional prognostic value during treatment.