Hydroxyurea for Non-Transfusion-Dependent β-Thalassemias: A Meta-Analysis
Bibliographic record
Abstract
Abstract Background Non-transfusion-dependent (NTD) β-thalassemia syndromes consist of β-thalassemia intermedia and moderate Hemoglobin E/ β thalassemias. They are characterized by varying degrees of chronic anemia and a wide spectrum of complications due to ineffective erythropoiesis and iron overload from chronic transfusions. Hydroxyurea, an oral chemotherapeutic drug, is anticipated to decrease disease severity by raising hemoglobin (Hb) levels and reducing transfusion requirements. Objectives To examine the evidence for clinical efficacy and safety of hydroxyurea in NTD β-thalassemia patients of any age. Search strategy We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ongoing trials registers, and major preceding conferences. Hand searches were also conducted using reference lists from primary studies. All searches were updated to June 5, 2014. Selection criteria Randomized controlled trials (RCTs) and observational studies (sample size ≥ 5) assessing the clinical efficacy of hydroxyurea alone for three months or longer, for the treatment of patients with NTD β-thalassemia were included. Data collection and analysis Two authors acted as reviewers and independently assessed study quality and extracted data from the included studies. Authors of included studies were contacted if further information was required. NTD β-thalassemia was sub-classified into two groups; mild (no or < 4 transfusion per year) and severe (≥4 transfusions per year). The effect size was estimated as a proportion (responders over sample size). For Mild-NTD-β-thalassemia, response rate (RR) was identified as a ≥10g/dL increase in Hb. In Severe-NTD-β-thalassemia, overall response rate (ORR) was defined as ≥ 50% reduction in transfusion need and complete response rate (CRR) was defined as complete cessation of regular transfusion. All data was analyzed using Stata, Version 13.0. Results For Mild-NTD β-thalassemia, a total of 14 studies (1 RCT and 13 observational studies) involving 344 patients met inclusion criteria. Hydroxyurea therapy was effective in raising Hb by 10g/dL from baseline in 56% (95% CI, 46-67%). In Severe-NTD-β-thalassemia, 8 studies (1 RCT and 7 observational studies) involving 305 patients were included. Hydroxyurea was associated with a statistically significant decrease in transfusion need with CRR of 53% (95% CI, 37-70%) and ORR of 79% (95% CI, 68-91%). All of the studies had several limitations, such as small sample size, lack of comparison group, under-reporting of data and methods, and the majority having been observational studies. Adverse events (AEs) were transient and improved with temporary cessation of the drug and/or adjustment of the dose. Author’s conclusion Hydroxyurea appears to be effective in the management of NTD β-thalassemia (both mild and severe forms) by raising the Hb by at least 10g/dL and decreasing the need for chronic blood transfusions completely or partially, respectively, in the majority of patients. It appears to be well tolerated and associated with mild and transient AEs. Patients with NTD β-thalassemia may benefit from a trial of hydroxyurea, though large RCTs assessing efficacy should be done to confirm the findings of this meta-analysis. Disclosures Off Label Use: Hydroxyurea for β-Thalassemia.
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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 | 0.012 | 0.022 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.017 | 0.044 |
| Bibliometrics | 0.004 | 0.005 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.006 | 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".