Meta-Analysis Of The Efficacy And Safety Of Combined Chelation Therapy In Patients With Thalassemia Major

Objective To evaluate the efficacy and safety of deferiprone in combination with deferoxamine in treatment of patients with thalassemia major by meta-analysis.Methods The clinical references were selected from data of Cochrane library,PubMed,Ovid,Springer,CBMdis,CNKI and VIP,in which articles published from January 1,1985 to May 31,2008 were searched by using the terms of Deferipron and Deferoxamine and thalassemia for human clinical trials. Two reviewers independently performed data extraction and assessed the quality of included studies.Chose serum ferritin(SF),liver iron concentration(LIC), myocardial iron content,drug adverse reaction,total iron excretion and cardiac function as evaluation indexes,which of them were selected to evaluate the combined WMD or SMD or RR value and 95%confidence interval(CI). Extracted data were inputed and analyzed by software of Review Manager 4.3.2, recommended by Cochrane Collaboration.Results Five randomized controlled studies involving 230 patients were included.Only one of the five trials was double-blind study.Compared combined therapy group(deferiprone 5～7d/w plus deferoxamine twice weekly) to control group(deferoxamine monotherapy for 5～7d/w),Meta-analysis based on included studies showed:the changes of SF and LIC before and after therapy were(SMD=-0.04,95%CI:-0.48～0.41),(SMD=-0.14,95%CI:-0.59～0.30) respectively,the total iron excretion(WMD=0.18,95%CI:0.00～0.37),there were no statistical significant differences between the two groups.The improvement of left ventricular ejection fraction(WMD=3.40,95%CI:0.97～5.82)was higher in combined therapy group than those in control group.The incidence of gastrointestinal symptoms(RR=2.75,95%CI:1.40～5.40) was higher in combined therapy group,but there were no significant differences in the arthrosis side effect(RR=1.45,95%CI:0.59～3.52),the incidence of neutropenia(RR=0.85,95%CI:0.27～2.66) and the reactions at the infusion site (RR=0.55,95%CI:0.19～1.60).The evidence was not strong enough to judge whether the combined chelation therapy was superior to deferoxamine monotherapy due to only one RCT study evaluated myocardial iron by which MRIT2~* was enrolled.Conclusions Available evidence showed combined chelation therapy (deferiprone for 5～7d/w plus deferoxamine twice weekly) was as effective as deferoxamine monotherapy(5～7d/w) and may be superior to deferoxamine monotherapy in improving myocardial siderosis and heart function,the common side effect was gastrointestinal symptoms.Combined chelation therapy was not only effective but also can reduce the pain from long-term deferoxamine infusion,and this should translate into improved survival rate and patient compliance.