The effect and side effect of hydroxyurea therapy on patients with β-thalassemia: a systematic review to December 2012.

Hydroxyurea (HU) is being used for patients with transfusion-dependent β-thalassemia major (β-TM) as well as non transfusion-dependent β-TM. As controversy exists regarding efficacy and safety of HU, we searched the published literature on efficacy, effectiveness and toxicity of HU in patients with β-TM. The research sources we used were: Medline, SID, PubMed, Scopus, Request, Web of Knowledge, Springer, Ovid, Cochrane searched up to October 2012. Using search terms sensitive to studies of clinical trials combined with searches on terms related to thalassemia and HU. We selected studies on randomized trials, quasi experimental trials (before and after design), case reports (with 1-5 cases), side effect studies in patients with β-TM, studies related to the mechanism of action and toxicity when used in patients with other hemoglobinopathies. We researched studies in English and Persian. Eligible articles were reviewed by two independent reviewers. Patient's characteristics, duration of trial, outcome and side effects were extracted. The main outcomes were synthesized under a random-effects model. Heterogeneity was assessed using the Q statistic, Tau(2) and I(2). Subgroup analyses were performed and the statistics data (STATA) software used. More than 500 articles were reviewed. No randomized clinical trial was found. Seventeen trials with before and after designs were found, 16 case reports (1-5 cases), 19 articles for mechanism of action and 16 studies for side effects were published from 1969 to October 2012. Hemoglobin levels after treatment showed modest but significant increase in non transfusion-dependent β-TM (p < 0.0001) and in transfusion-dependent β-TM (p < 0.0001).