Safety and efficacy of thrombopoietin‐receptor agonists in myelodysplastic syndromes: a systematic review and meta‐analysis of randomized controlled trials
Bibliographic record
Abstract
Thrombocytopenia is common (40-65%) and potentially serious in myelodysplastic syndromes (MDS). A systematic review was conducted to determine the safety and efficacy of adding a thrombopoietin-receptor (THPO-R) agonist to standard MDS treatment. MEDLINE, EMBASE and CENTRAL databases were searched. We included randomized controlled trials comparing a THPO-R agonist to placebo. A meta-analysis of the effects was performed. Endpoints included bleeding and platelet transfusion rates, risk of progression to acute myeloid leukaemia (AML) and mortality. Three hundred and eighty four patients from five trials were included, four using romiplostim and one using eltrombopag. Overall, the relative risk (RR) of bleeding with romiplostim versus placebo was 0·84 [95% confidence interval (CI): 0·57-1·24]. However, compared to placebo, romiplostim significantly decreased the exposure-adjusted bleeding rate (RR 0·92; 95% CI: 0·86-0·99), as well as the exposure-adjusted platelet transfusion rate (RR 0·69; 95% CI: 0·53-0·88). The RR of AML progression with romiplostim was 1·36 (95% CI: 0·54-3·40), however the outcome data were judged as higher risk of bias. Romiplostim is promising in its ability to decrease patient-important outcomes: bleeding and platelet transfusion need. Although the risk of AML progression was not increased, due to unclear risk of bias in the data, this safety concern is difficult to assess. Therefore, romiplostim cannot yet be routinely recommended. Early eltrombopag data is promising.
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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 | 0.015 | 0.027 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.021 | 0.028 |
| Bibliometrics | 0.006 | 0.007 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".