Impact of c-KIT and FLT3 mutations on survival outcomes in core-binding factor acute myeloid leukemia: A systematic review and meta-analysis
Bibliographic record
Abstract
Abstract Background: Core-binding factor acute myeloid leukemia (CBF-AML) is generally considered a favorable-risk subtype; however, prognosis varies based on co-occurring genetic alterations. Among these, c-KIT and FLT3 mutations have been proposed as adverse prognostic markers, though data remain inconsistent. We performed a systematic review and meta-analysis to clarify the prognostic impact of c-KIT and FLT3 mutations in CBF-AML, with subgroup analysis according to cytogenetic subtype [t(8;21) vs. inv(16)]. Methods: All observational studies including CBF-AML patients identified from Embase, PubMed, and Cochrane Library were evaluated. Eligible studies reported hazard ratios (HR) with 95% confidence intervals (CI) for overall survival (OS), disease-free survival (DFS), event-free survival (EFS), leukemia-free survival (LFS), relapse-free survival (RFS), or cumulative incidence of relapse (CIR). The generic inverse variance method was used for pooling. Subgroup analyses were conducted by cytogenetic subtype and by concomitant gene mutation (c-KIT, FLT3-ITD, and FLT3-TKD). Results: Seventeen studies met the inclusion criteria. Presence of c-KIT mutation was associated with significantly worse outcomes, including decreased OS (pooled HR 2.02; 95% CI 1.52–2.67; I² = 59%) and RFS (HR 1.89; 95% CI 1.44–2.50; I² = 57%), as well as increased CIR (HR 2.24; 95% CI 1.42–3.55; I² = 45%). This effect was primarily driven by the t(8;21) subgroup, where c-KIT mutations were strongly associated with inferior OS (HR 2.85; 95% CI 1.65–4.93; I² = 69%), EFS (HR 2.60; 95% CI 1.81–3.74; I² = 59%), and CIR (HR 2.43; 95% CI 1.46–4.05; I² = 37%). In contrast, among patients with inv(16), c-KIT mutations were not significantly associated with OS (HR 1.30; 95% CI 0.73–2.29; I² = 37%), EFS (HR 1.22; 95% CI 0.71–2.07; I² = 4%), or CIR (HR 1.54; 95% CI 0.88–2.69; I² = 0%). FLT3 mutations showed no significant prognostic impact, with pooled HRs for OS of 1.28 (95% CI 0.83–1.98; I² = 25%) and for RFS of 1.32 (95% CI 0.91–1.92; I² = 31%), and no difference between ITD and TKD subtypes. Conclusion: This meta-analysis demonstrates that c-KIT mutations, particularly in patients with t(8;21) CBF-AML, are strongly associated with inferior survival and higher relapse rates, whereas FLT3 mutations do not significantly impact outcomes. These findings highlight the need for risk-adapted therapeutic strategies in CBF-AML, with consideration for more intensive or targeted approaches in c-KIT–mutated t(8;21) patients.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.009 | 0.023 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.016 | 0.029 |
| Bibliometrics | 0.006 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".