Genetic factors rather than blast reduction determine outcomes of allogeneic HCT in <i>BCR-ABL</i>–negative MPN in blast phase
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Bibliographic record
Abstract
There is a limited understanding of the clinical and molecular factors associated with outcomes of hematopoietic cell transplantation (HCT) in patients with BCR-ABL-negative myeloproliferative neoplasms in blast phase (MPN-BP). Using the Center for International Blood and Marrow Transplant Research database, we evaluated HCT outcomes in 177 patients with MPN-BP. Ninety-five (54%) had sufficient DNA for targeted next-generation sequencing of 49 genes clinically relevant in hematologic malignancies. At 5 years, overall survival (OS), cumulative incidence of relapse, and nonrelapse mortality of the study cohort was 18%, 61%, and 25%, respectively. In a multivariable model, poor-risk cytogenetics was associated with inferior OS (hazard ratio [HR], 1.71; 95% CI, 1.21-2.41) due to increased relapse (HR, 1.93; 95% CI, 1.32-2.82). Transplants using mobilized peripheral blood (PB) were associated with better OS (HR, 0.60; 95% CI, 0.38-0.96). No difference in outcomes was observed in patients undergoing HCT with PB/BM blasts <5% vs those with active leukemia. Among the 95 patients with molecular data, mutation of TP53, present in 23%, was the only genetic alteration associated with outcomes. In a multivariate model, TP53-mutant patients had inferior OS (HR, 1.99; 95% CI, 1.14-3.49) and increased incidence of relapse (HR, 2.59; 95% CI, 1.41-4.74). There were no differences in the spectrum of gene mutations, number of mutations, or variant allele frequency between patients undergoing HCT with PB/BM blasts <5% vs those with active leukemia. Genetic factors, namely cytogenetic alterations and TP53 mutation status, rather than degree of cytoreduction predict outcomes of HCT in MPN-BP. No meaningful benefit of conventional HCT was observed in patients with MPN-BP and mutated TP53.
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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) | 0.000 | 0.000 |
| 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 | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it