Treatment of MDS Related Transfusion-Dependent Anemia with Epoetin alfa: A Meta-Analysis Perspective.
Bibliographic record
Abstract
Abstract Background: Regular transfusion dependence is seen in almost every MDS patient (pt) during the natural course of disease. Due to deleterious sequelae of chronic transfusions, including iron-overload, alloimmunization, and infections, delaying transfusion dependence or attainment of transfusion-independence are important MDS treatment goals. The role of epoetin alfa (EPO) is well established for anemia treatment prior to transfusion dependence, although its utility in transfusion-dependent pts is not well understood. The present meta-analysis was conducted to assess the efficacy of EPO in achieving transfusion independence in transfusion-dependent MDS pts. Methods: Data was extracted from studies from PubMed, ASCO and ASH proceedings from 1990–2006 in transfusion-dependent MDS pts treated with EPO±G/GM-CSF. Studies using International Working Group (IWG) response and IWG-like criteria with EPO±G/GM-CSF were compared with EPO monotherapy studies not using IWG criteria (Non-IWG). Pooled estimates of erythroid response (ER) rates were calculated using random-effects models. Where only pre-therapy values were available, values for post-therapy reductions in RBC requirements (units/month) were imputed based on response criteria stated in the study. Results: Included were 578 evaluable transfusion-dependent pts representing 58% of the total study population in 25 studies. All studies collectively showed significant treatment effects from baseline (BL) as evidenced by a mean overall ER rate of 34.5% and a mean proportion of pts achieving complete transfusion independence of 23.3% with EPO±G/GM-CSF (p<.001 for both). A significant decrease was observed in mean RBC units/month after treatment (2.55 pre-therapy vs 1.96 post-therapy,p=.0002,n=17 studies). IWG studies showed numerically higher ER rates and lower transfusion requirements than Non-IWG studies (Table) (p>.05). Among IWG studies, EPO monotherapy as compared to EPO±G/GM-CSF, showed comparable ER rates (41.6% vs 36.4%,p=.643), a comparable proportion of pts achieving transfusion-independence (28.8% vs 24.8%,p=0.705), and a greater reduction in RBC units/month (34.3% vs 10.4%,p=0.339). Additionally, EPO monotherapy IWG studies showed dose response with significantly higher overall ER rates in pts receiving 60-80,000 units/week vs 30-40,000 units/week (45.3% vs 30.8%,p=.041). Multivariate regression did not yield significant association of any BL study characteristics with overall ER rate. Conclusion: Findings from this meta-analysis showed EPO±G/GM-CSF treatment is effective in reducing transfusion requirements in transfusion-dependent MDS pts. Identification of predictors of EPO response in this population may offer significant clinical benefit to this subset. Study Group Non-IWG Studies IWG Studies IWG Studies EPOMonotherapy EPOMonotherapy EPO +G/GM-CSF No. of studies (evaluable pts) 12(268) 7(195) 6(115) BL sEPO levels, mU/mL (Mean±SD) 687.2±684.7 374.3±72.2 288±172.1 BL Hb, g/dL (Mean±SD) 8.5±0.6 7.9±0.4 8.1±0.4 Initial weekly dose of EPO, Units (Mean±SD) 48,310±41,345 49,326±22,752 34,789±12,083 Mean monthly pre-therapy RBC Units 2.71 2.37 2.33 Pooled ER rate, % (95%CI) 27.8(20.4–35.2) 41.6(24.5–58.6) 36.4(22.5–50.2) Post-therapy transfusion-independent pts, % (95%CI) 17.9(10.9–24.9) 28.8(12.6–45.1) 24.8(11.8–37.8) Mean post-therapy reduction in RBC units/month, % (Median) 17.3(17.1) 34.3(24.7) 10.4(11.5)
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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 | 0.011 | 0.018 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.014 | 0.033 |
| Bibliometrics | 0.004 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 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".