Comparison of Erythroid Response (ER) Rates in Myelodysplastic Syndromes (MDS) Patients Treated with Different Therapeutic Strategies Using Epoetin Alfa (EPO).
Bibliographic record
Abstract
Abstract Background: EPO continues to be a primary therapeutic choice for the treatment of anemic patients with low to intermediate-1 risk MDS. Initially, without standardized response criteria, ER rates were modest. Recently, a meta-analysis of EPO monotherapy studies in MDS demonstrated a significant improvement in ER rates with the application of standardized International Working Group criteria (IWGc) for response evaluation (Moyo V et al. 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 6572). This meta-analysis was expanded to determine the impact of higher doses of EPO or the addition of granulocyte or granulocyte-macrophage colony stimulating factor (G- or GM-CSF) to EPO on ER rates (defined as major + minor response). Methods: A systematic review and data extraction of studies from PubMed, ASCO and ASH proceedings from 1990–2006 in MDS patients treated with EPO monotherapy or EPO + G-/GM-CSF combination therapy was performed. Pooled estimates of ER rates were calculated in studies defining ER rates without IWGc application (non-IWGc) for EPO monotherapy at Standard (std) dose (30,000–40,000 Units per week) in comparison to studies that defined ER rates using IWGc, where EPO was used at std dose or high dose (60,000–80,000 Units per week) or in combination with G-/GM-CSF. Results: A total of 23 studies were evaluated in this analysis. As shown in the table below the IWGc studies using EPO at std dose or high dose or in combination with G-/GM-CSF demonstrated significantly higher ER rates than the non-IWGc studies (p<0.001 for all comparisons). Among the IWGc studies, those using a higher dose of EPO alone had significantly higher ER rates as compared to studies using std dose EPO monotherapy (p<0.001) or EPO + G-/GM-CSF combination (p=0.018). In addition, among the studies using EPO combinations, those using EPO + G-CSF (Total studies-3, evaluable N= 96) showed ER rates of 55.2% as compared to 42.8% (p=0.142) for the EPO + GM-CSF combination (Total studies-3, evaluable N= 56). Conclusions: The findings from this present meta-analysis confirm the impact of IWGc on ER rates for EPO therapy previously observed. Further improvement in ER rates was observed with the use of higher doses of EPO alone or the combination of EPO + G-/GM-CSF. Increasing the EPO dose appeared to have a greater impact on ER than the addition of G-/GM-CSF. Non-IWGc IWGc Study Group EPO Std Dose EPO Std Dose EPO High dose EPO + G-/GM-CSF Starting EPO Dose Units/week 30,000–40,000 30,000–40,000 60,000–80,000 30,000–40,000 No. of Studies 8 5 4 6 No.of Evaluable Patients 262 393 196 152 ER Rates (%)(95% CI) 32.1 (26–38) 47.8 (43–53) 63.3 (57–70) 50.7 (42–59)
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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 | 0.024 | 0.040 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.010 | 0.020 |
| Bibliometrics | 0.004 | 0.004 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 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".