PS1466 CYTOREDUCTION FOR THE TREATMENT OF ESSENTIAL THROMBOCYTHEMIA: A SYSTEMATIC REVIEW
Bibliographic record
Abstract
Background: Cytoreductive therapies are recommended in patients with essential thrombocythemia (ET) to prevent arterial and venous thrombosis. Aims: The aim of this study was to systematically review the benefits and harms of different cytoreductive therapies in adult patients diagnosed with ET. Methods: We searched MEDLINE, EMBASE, FDA, and EMA databases from inception through 23 January 2017 for randomized trials and prospective observational studies in English evaluating first‐line cytoreduction in ET patients diagnosed by WHO or PVSG criteria. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool for randomized controlled trials, and the MINORS criteria for observational studies. Results: We found 34 studies involving 6791 participants: 3 randomized controlled trials (RCT), and 31 prospective observational studies. In the single trial comparing hydroxyurea versus placebo, hydroxyurea reduced arterial thromboembolism (ATE) (RR 0.13 [95%CI 0.03–0.54]) and venous thromboembolism (VTE) (RR 0.52 [95%CI 0.05–5.55]), increased transformation to MDS or AML (RR 9.32 [95%CI 0.51–169.13]), with no difference in mortality (RR 1.09 [95%CI 0.45–2.62]). In a trial from 2013, Anagrelide was non‐inferior to hydroxyurea in ET‐related major and minor thrombohemorrhagic events (HR 0.92 [95% CI, 0.57–1.46] at 36 months). There were no reported events of disease progression to myelofibrosis (MF) or secondary leukemia. In an RCT from 2007 comparing anagrelide plus aspirin and hydroxyurea plus aspirin, anagrelide was associated with increased rates of arterial thrombosis (p = 0.004), serious hemorrhage (p = 0.0008), and transformation to MF (p = 0.01). However, there was a decreased rate of venous thromboembolism (VTE) (p = 0.006). Observational studies evaluated the cytoreductive therapies anagrelide (n = 1930), hydroxyurea (n = 898), interferon alpha (n = 453), and pipobroman (n = 270). Overall, of patients treated with anagrelide, there was 6.3% all‐cause mortality, 0.7% VTE, 3.3% ATE, and 5.5% major bleeding complications. Rates of transformation were 3.3% to MF, 0.3% to acute myeloid leukemia (AML), and 0.1% to myelodysplastic syndrome (MDS). In patients treated with hydroxyurea, there was 5.8% all‐cause mortality, 4.3% VTE, 3.8% ATE, and 4.8% major bleeding. Rates of transformation were 0.8% to MF, 1.2% to AML and 0.5% to MDS. Patients treated with interferon alpha had 2.5% all‐cause mortality, 5.4% VTE, 0.6% ATE, and 2.0% major bleeding. Rates of transformation were 4.2% to MF, 1.1% to AML, and no reported transformation to MDS. Of patients treated with pipobroman, there was 15.3% all‐cause mortality, 2.9% VTE, 7.2% ATE, and 1.2% major bleeding. Rates of transformation were 0.7% to MF, 2.6% to AML, and 0.7% to MDS. In patients who did not receive any cytoreductive therapy, all‐cause mortality was 15.5%, with 6.0% VTE, no reported ATE, and 6.9% major bleeding. There were no cases of transformation to MF, AML, or MDS. Most observational studies were at high risk of bias due to lack of adjustment for potential confounders. Summary/Conclusion: In patients with ET, hydroxyurea may reduce ET‐related thrombotic events compared to placebo. A single randomized controlled trial and low quality observational data may suggest that anagrelide has decreased rates of venous thromboembolism and increased rates of arterial thromboembolism, hemorrhage, and transformation to myelofibrosis compared to hydroxyurea. However, all studies had significant risk of bias with critical implications for guideline recommendations and the need for new research.
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.006 | 0.002 |
| 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 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".