| PART I Role of cytarabine in acute promyelocytic leukemia(APL) treatment: a cochrane systematic reviewObjectives This systematic review assesses the efficacy and safety of cytarabine (Ara-C) for the treatment of acute promyelocytic leukemia(APL).Methods We searched the Cochrane Library (Issue 3, 2008), Cochrane Register of Clinical Trials(CENTRAL,1970-2008.8), Medline(1978-2008.4), EMBASE(1990-2008.8), CBM(1978-2008), CNKI(1994-2008),VIP(1989-2008),CMAC(1994-2008).We also seached the Current Controlled Trials,the the National Research Register,Conference Proceedings of American Society of Hematology(2004-2007) and American Society of Clinical Oncology(2005-2007), OpenSIGLE,HMIC and NTIS on the internet.We handsearched the related journals in the library of Third Military Medical University. We included randomized clinical trials(RCT), which studied the efficacy and safety of Ara-C in APL treatment, by comparison of therapeutical strategy with Ara-C and treatment strategy without. The include trials were graded methodologically. Two authors at least, indenpdently selected studies and extracted data. The data was input and analysed with the latest Cochrane review manager software(RevMan 5.0).Results Three eligible RCTs were included (N=504 ). Meta analysis showed that adding Ara-C to the treatment of APL had no statistically significant effects on event free survival (EFS) (HR 1.21,95%CI 0.93,1.59), overall survival(OS)(HR1.02,95%CI 0.80,1.31) and disease free survival(DFS). Ara-C for the treatment of APL also had no significant influences on complete remission(CR), induction death, toxic and adverse reaction. The influence of adding Ara-c to relapse rate(RR) is still controversial.Conclusion This systematic review found that adding Ara-C for the treatment of APL was not beneficial based on the currently available data. PART II Role of arsenic trioxide in APL treatment: Cochrane systematic reviewsSectionâ… Arsenic trioxide(ATO) monotherapy for APL treatment:a cochrane systematic reviewObjectives This systematic review is aiming to assess the efficacy and safety of ATO monotherapy for the treatment of APL.Methods We searched the Cochrane Library (Issue 1, 2009), CENTRAL(1970-2009.1), Medline(1978-2008.10),EMBASE(1950-2009.3), CBM(1978-2008), CNKI(1994-2008) ,CMAC(1994-2008).We also seached the metaregister,Conference Proceedings of American Society of Hematology(1946-2008) and Conference Proceedings of American Society of Clinical Oncology(2004-2008) on the internet for grey literature.We handsearched the related journals in the library of Third Military Medical University. We included RCT which compared regimen containing ATO with regimen without ATO for the treatment of APL. We adopt CR,OS,DFS,time to CR, RR,mortality and adverse reactions as result indicators. Data was input and analysed with the Cochrane review manager software 5.0(RevMan 5.0).Results Five eligible RCTs were included (N=328). All the RCTs were mainly focusing on the comparison of ATRA plus ATO regimen with ATRA monotherapy. Meta analysis showed that effect index for time to CR, 2-year DFS,RR and incidence of edema were-1.20 days(-1.68,-0.72), 8.37(1.64,42.60),0.20(0.08,0.52)and 4.16(1.46,11.79), respectively. The influence on other reslult indicators such as CR, leukocytosis , et al are statistically non-significant.Conclusion: ATO can improve DFS and reduce the time to CR and RR of newly diagnosed APL patients, but it will increase the incidence of edema during treatment. Due to limitation of the included trials, this conclusion need to be validated by further studies.Sectionâ…¡Comparison of efficacy of ATO versus ATRA for APL treatment: a Cochrane systematic reviewObjectives This systematic review compares the efficacy and safety of ATO with ATRA for the treatment of APL.Methods We searched the Cochrane Library (Issue 1, 2009), CENTRAL(1970-2009.1), Medline(1978-2008.10),EMBASE(1950-2009.3), CBM(1978-2008), CNKI(1994-2008) ,CMAC(1994-2008); We also seached the metaregister,Conference Proceedings of American Society of Hematology(1946-2008) and American Society of Clinical Oncology(2004-2008) on the internet for grey literature.We handsearched the related journals in the library of Third Military Medical University. We included RCTs which compared ATO with ATRA for the treatment of APL. We adopt CR,OS,DFS,time to CR, RR,mortality and adverse reactions as result indicators. Data was imput and analysed with the Cochrane review manager software(RevMan 5.0).Results Four eligible RCTs were included (N=243). All the RCTs were methodologically graded as B. They all are focusing on the comparison of ATO monotherapy with ATRA monotherapy in treating newly diagnosed APL patients. Meta analysis showed that effect index for CR, 2-year DFS,time to CR,RR and mortality is 0.96(0.50,1.86),2.76(0.71,10.66),-1.30days(-1.83,-0.78), 0.86(0.45,1.63),1.15(0.45,2.95),respectively,all indicate no statisticaly significant difference. Effect index for incidence of liver dysfunction is 3.03(1.25,7.37),which shows statistically significant difference between ATO group and ATRA group..Conclusion ATO is not superior to ATRA in treating newly diagnosed APL patients regarding CR,DFS,time to CR,RR and mortality. What is worse, it will increase the incidence of liver dysfunction during treatment. Due to limitation of included trials, this comclusion need to be validated by further studies.Sectionâ…¢ATO in combination with ATRA for APL treatment: a cochrane systematic reviewObjective To assess the efficacy and safety of ATO in combination with ATRA for the treatment of APL.Methods Cochrane Library (Issue 1, 2009), CENTRAL(1970-2009.1), Medline (1978-2008.10), EMBASE(1950-2009.3), CBM(1978-2008), CNKI(1994-2008), CMAC(1994-2008) were searched. the metaregister, Conference Proceedings of American Society of Hematology(1946-2008) and American Society of Clinical Oncology(2004-2008) on the internet were also searched for grey literature. The authors also hand-searched Chinsese periodicals potentially realated to the question including Chinese Journal of Hematology, Journal of Experimental Hematology and Journal of Clincal Hematology. All randomizde controlled trials comparing ATO+ATRA with other regimens for the treatment of APL were included. Two reviewers selected studies,appraised the quality of studies, and extracted the data independently. The eligible studies were evaluated and extracted data was analysed with Cochrane Review Manager 5.0. Results Seven eligible RCTs were included (N=392). Six RCTs were methodologically graded as middle and one as high risk of bias. The control group include ATO monotherapy, ATRA monotherapy and ATO+ATRA+chemotherapy. Compared with ATO monotherapy, ATO+ATRA combination can improve time to CR and RR of newly diagnosed APL,but can not improve CR rate,DFS,mortality and liver dysfunction of relapsed APL patients based on meta-analysis and sensitivity analysis; Compared with ATRA monotherapy, ATO+ATRA combination can improve time to CR, DFS and RR, but may increase the incidence of edema during treatment; Compared with ATO+ATRA+chemotherapy, ATO+ATRA can impove CR, RR, mortality and adverse reactions.Conclusion The reslults of meta-analysis and sensitivity analysis indicate that:â‘ For newly diagnosed APL, ATO+ATRA combination is superior to ATO monotherapy, ATRA monotherapy and ATO+ATRA+chemotherapy, but due to the lack of data about comparison with the current standard treatment regimen(ATRA+chemotherapy), it is not enough to recommend ATO+ATRA as frontline therap;â‘¡For relapsed APL, ATO+ATRA combination is not superior to ATO monotherapy, it is not supportive of adding ATRA to ATO monotherapy. But due to limitation of sample size and risk of bias of included trials, the effect of ATO+ATRA combination need to be confirmed by large and high-quality RCTs.
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