Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Myelofibrosis with Prior Exposure to Janus Kinase 1/2 Inhibitors
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Bibliographic record
Abstract
The impact of Janus kinase (JAK) 1/2 inhibitor therapy before allogeneic hematopoietic cell transplantation (HCT) has not been studied in a large cohort in myelofibrosis (MF). In this retrospective multicenter study, we analyzed outcomes of patients who underwent HCT for MF with prior exposure to JAK1/2 inhibitors. One hundred consecutive patients from participating centers were analyzed, and based on clinical status and response to JAK1/2 inhibitors at the time of HCT, patients were stratified into 5 groups: (1) clinical improvement (n = 23), (2) stable disease (n = 31), (3) new cytopenia/increasing blasts/intolerance (n = 15), (4) progressive disease: splenomegaly (n = 18), and (5) progressive disease: leukemic transformation (LT) (n = 13). Overall survival (OS) at 2 years was 61% (95% confidence interval [CI], 49% to 71%). OS was 91% (95% CI, 69% to 98%) for those who experienced clinical improvement and 32% (95% CI, 8% to 59%) for those who developed LT on JAK1/2 inhibitors. In multivariable analysis, response to JAK1/2 inhibitors (P = .03), dynamic international prognostic scoring system score (P = .003), and donor type (P = .006) were independent predictors of survival. Among the 66 patients who remained on JAK1/2 inhibitors until stopped for HCT, 2 patients developed serious adverse events necessitating delay of HCT and another 8 patients had symptoms with lesser severity. Adverse events were more common in patients who started tapering or abruptly stopped their regular dose ≥6 days before conditioning therapy. We conclude that prior exposure to JAK1/2 inhibitors did not adversely affect post-transplantation outcomes. Our data suggest that JAK1/2 inhibitors should be continued near to the start of conditioning therapy. The favorable outcomes of patients who experienced clinical improvement with JAK1/2 inhibitor therapy before HCT were particularly encouraging, and need further prospective validation.
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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) | 0.000 | 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