High IL1R1 expression predicts poor survival and benefit from stem cell transplant in intermediate-risk acute myeloid leukemia from the Leucegene cohort
Bibliographic record
Abstract
Abstract Background There is an unmet clinical need to identify patients with acute myeloid leukemia and intermediate-risk cytogenetics who benefit from allogeneic hematopoietic stem cell transplantation in first remission, especially among those without FLT3-ITD mutation. Methods We analyzed transcriptomic data from the Leucegene cohort composed of 316 patients with acute myeloid leukemia and intermediate-risk cytogenetics who have been treated with intensive chemotherapy. We evaluated associations between gene expression and overall survival or relapse-free survival and we analyzed the interaction between gene expression and allogeneic hematopoietic stem cell transplantation to identify biomarkers that predict the benefit of stem cell transplantation in this subgroup of patients. Results We identified high IL1R1 expression (IL1R1high) as a prognostic and predictive marker in the Leucegene cohort. IL1R1high (≥ 2.0 transcripts per million) was associated with older age, monocytic differentiation, higher frequency of FLT3-ITD and RUNX1 mutations and lower frequency of IDH1/2 and bZIP CEBPA mutations. Patients with IL1R1high had lower 5-year overall survival (10% vs 38%, p < 0.01), and higher 5-year cumulative incidence of relapse (76% vs 59%, p < 0.01) than those with low IL1R1 expression. IL1R1high was independently associated with overall survival in multivariable analyses including age, white blood cell count at diagnosis and NPM1, FLT3-ITD, bZIP CEBPA, RUNX1, ASXL1 and DNMT3A mutations (HR 1.78, p < 0.01). Importantly, in landmark analysis, hematopoietic stem cell transplantation in first remission significantly improved 5-year overall survival in patients with IL1R1high (67% vs 27%, HR 0.33, p < 0.01), but not in patients with IL1R1low (62% vs 54%, HR 0.72, p = 0.31), especially among those without FLT3-ITD mutation (48% vs 50%, HR 0.93, p = 0.85). In patients who proceeded to allogeneic hematopoietic stem cell transplantation, the 5-year overall survival was 60% in patients with IL1R1high compared to 56% in patients with IL1R1low confirming that the worse prognosis associated with high expression of IL1R1 was abrogated by stem cell transplantation. Conclusion IL1R1 expression is a candidate marker to identify patients with intermediate-risk cytogenetics acute myeloid leukemia at high risk of relapse who benefit from allogeneic hematopoietic stem cell transplantation in first remission.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.015 | 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 teacher head, 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".