Erythroid Response (ER) Rates in Myelodysplastic Syndromes (MDS) Patients Treated with Epoetin Alfa (EPO) or Darbepoetin Alfa (DARB) Using International Working Group Response Criteria (IWGc): Comparative Meta-Analysis.
Bibliographic record
Abstract
Abstract Background: EPO has been used in the treatment of refractory anemia in MDS patients for many years. Recently, with the identification of definitive patient selection criteria (low serum EPO [sEPO] levels and receipt of minimal transfusions) and standardization of ER rate evaluation methods using the IWGc, response to EPO therapy has been shown to be significantly enhanced in low/int-1 risk MDS patients. The present meta-analysis was conducted to compare ER rates (defined as major + minor response) of the two erythropoiesis-stimulating therapies (ESTs) currently available in the US, EPO and DARB, in MDS patients who were selected and evaluated for ER using the aforementioned uniform criteria. Methods: A systematic review and data extraction of studies from PubMed and ASCO/ASH proceedings from 1990–2006 in MDS patients treated with EPO monotherapy and from 2003–2006 in those treated with DARB monotherapy was performed. Pooled estimates of ER rates were calculated in each group using random-effects meta-analysis methods, which incorporated both between- and within-group variations. Multivariate meta-regression analysis was further conducted to control for differences in baseline characteristics between the two groups. Results: Nine EPO studies (N=619 patients, N evaluable for ER rate =589) and 8 DARB studies (N=442, N evaluable for ER rate =389) were identified. Baseline characteristics were comparable between the two groups with respect to age, gender, mean baseline hemoglobin, transfusion dependency rates, and proportion of patients with refractory anemia/refractory anemia with ringed sideroblasts. The mean baseline sEPO levels were significantly higher in the EPO group, compared to the DARB group (376: range 43–418; vs. 133: range 68–303 mU/mL, p=0.0026). The average initial weekly dose in the EPO studies was 47,851 (range: 30,000–80,000) Units, while that in the DARB studies was 176 (range: 100–315) mcg. There was no significant difference in the pooled estimate of the ER rates for either EST (57.6%: 95% CI; 45–70) for the EPO studies vs. (59.4%: 95% CI; 49–70) for the DARB studies, (p=0.8282). Further, as compared to the studies with standard doses of the two ESTs per week (EPO 30,000–40,000 Units; DARB ≤ 150 mcg), those using higher doses of EPO (60,000–80,000 Units) or DARB (>150 mcg) per week showed significantly higher ER rates (EPO- 47.8% vs. 63.3%, p<0.001; DARB −52.6% vs. 71.1%, p<0.001). Conclusions: This current meta-analysis demonstrates that, with the use of standardized patient selection and response evaluation methods, the two clinically available ESTs yield comparable ER rates in MDS patients.
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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 | 0.017 | 0.025 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.010 | 0.039 |
| Bibliometrics | 0.005 | 0.004 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".