Objective To systematically review the effectiveness and safety of arsenic trioxide (ATO) versus retinoic acid for patients with acute promyelocytic leukemia (APL). Methods Such databases as PubMed, The Cochrane Library (Issue 12, 2012), CNKI, WanFang Data and VIP were electronically and comprehensively searched from inception to December 2012, for randomized controlled trials (RCTs) on the effectiveness and safety of ATO versus retinoic acid for patients with APL. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality. Then, meta-analysis was performed using RevMan 5.0.2 software. Results Eight RCTs involving 586 cases of APL patients. The results of meta-analysis showed that, ATO and all-trans-retinoic (ATRA) were not statistically different in CR rates (OR=0.85, 95%CI 0.54 to 1.35, P=0.50), CR time (OR=–8.14, 95%CI –16.42 to 0.13, P=0.05), recurrence rates (OR=0.14, 95%CI 0.02 to 1.21, P=0.07), early mortality (OR=0.82, 95%CI 0.32 to 2.06, P=0.67), and five-year total survival rates (OR=1.19, 95%CI 0.54 to 2.60, P=0.66). ATO had lower incidences of adverse reaction such as hyperleukocytosis syndrome (OR=0.32, 95%CI 0.18 to 0.58, P=0.000 1) and retinoic acid syndrome (OR=0.05, 95%CI 0.02 to 0.14, Plt;0.000 01). Conclusion ATO and ATRA are alike in CR rates, CR time, recurrence rates, early mortality, and five-year total survival rates, but ATO causes less adverse reaction. Due to the limited quantity and quality of the included studies, ATO should be applied with caution according to patients’ conditions in clinic.
Objective To search evidence in the treatment of Philadelphia chromosome （Ph）-positive acute lymphocytic leukemia （ALL） for guiding chnical practice. Methods We searched MEDLINE （February, 1970～July, 2005 ） and SUMSEAILCH （till July, 2005 ）to identify systematic reviews（SIL）, randomized controlled trials（RCTs） and controlled clinical trials （CCTs） in the treatment of Ph-positive ALL. Results One RCT and 8 CCTs were identified. The results showed that Ph-positive ALL had a very poor prognosis . Chemotherapy and bone marrow transplantation （BMT） were the two main ways to treat the disease. Outcome of conventional chemotherapy treatment for adults with the disease was poor. Outcome of treatment with hyper-CVAD and imatinib mesylate was better and BMT was the only way which could potentially cure the disease. Conclusions Treatment of Ph-positive ALL with hyper-CVAD and imatinib mesylate may induce higher remission rate and disease free survival rate. BMT is the best way to cure the disease.
Objective To assess the clinical effectiveness and safety of inductive treatment with arsenic trioxide （As203） for acute promyelocytic leukemia （APL）. Methods Randomized controlled trials （RCTs） were identified from MEDLINE （1966 -July, 2005 ）, EMBASE （1984 -July, 2005 ）, The Cochrane Library （ Issue 3, 2005） and CBM- disc （1978 -July, 2005）. The references of eligible studies were handsearched. RCTs of As203 treating for APL were included. Data were evaluated and extracted by two reviewers independently with designed extraction form. RevMan 4. 2.7 software was used for data analysis. Results Six RCTs involving 323 patients were included. Two studies reported that there was no statistical difference between As2O3 group and all-transretinoic acid （ATRA） group in mortality for patients with APL or APL patients with complications of desseminated intiavascular coagulation or cerebra hemorrhage. The pooled result of 4 studies showed that there was no statistical difference with RR 0.98, 95 % CI 0.86 to 1.12 in complete remission （CR） rates between the two groups. The result of one study showed that the CR rate of patients with intravenous injection of As203 in 2 divided dosages with longer injection duration was higher with RR 1.31, 95% CI 0.86 to 1.12 compared with those with a single intravenous injection. Adverse effects in As2O3 group were less than ATRA group. Conclusions Inductive treatment with As2O3 for acute promyelocytic leukeuia has similar mortality and CR with less adverse effects compared with ATRA. More trials of high quality are required.
ObjectiveTo investigate the relationship between the expressions of B-cell-specific monoclonal leukemia virus insert site 1 (Bmi1) and human telomerase reverse transcriptase (hTERT) genes and the proliferative capacity of stem cells. MethodsCord blood CD34+ cells were cultured in IMDM medium containing fetal bovine serum, stem cell growth factor, thrombopoietin, and Fms-like tyrosine kinase 3 ligand during a 28-day ex vivo expansion process, while the expansion fold, specific growth rate, and the colony-forming efficiency were monitored. Then the Bmi1 and hTERT mRNA expressions in CD34+ cells were detected by fluorescence quantitative PCR, and the relations between the expressions and the cell proliferative capacity were analyzed. ResultsCD34+ cells expanded (20.1 ± 3.5) folds during the 28-day culture, while the proportion declined from 95.5% ± 2.6% before culture to 2.1% ± 0.4%. Both the specific growth rate and colony-forming efficiency of CD34+ cells declined significantly after 7 days, while the expression levels of Bmi1 and hTERT mRNA in CD34+ cells reached top at 7 days and declined gradually thereafter. ConclusionThe expressions of Bmi1 and hTERT genes may have a close relation to the proliferative capacity of CD34+ cells.
Objective To systematically evaluate the risk factors and population attributable risk of children leukemia in China, so as to provide references for policy-making. Methods The case-control studies about risk factors of children leukemia in China were searched in PubMed, CNKI, CBM, VIP and WanFang Data from inception to December 2011. According to the inclusion and exclusion criteria, two reviewers independently screened articles, extracted data, and evaluated the quality of the included studies. Then Meta-analysis was performed using STATA 11 and Excel 2003. The pooled odds ratio (OR) and 95% confidence interval (95%CI) of each risk factor were calculated, and the population attributable risk percent (PARP) based on the exposure rate of the risk factors was computed, and published bias was estimated according to the fail-safe number. Results A total of 15 case-control studies were included. The first 5 risk factors related to children leukemia were: dwelling environmental pollution (OR=2.782, 95%CI 2.268 to 3.413), house decoration (OR=2.525, 95%CI 1.736 to 3.673), maternal exposure to chemical hazards (OR=2.428, 95%CI 1.976 to 2.985), family history of tumor (OR=2.212, 95%CI 1.677 to 2.919), and child exposure to electromagnetic field around dwelling (OR=2.144, 95%CI 1.761 to 2.610). Factors with higher PARP were influenza history (37.56%), house decoration history (32.95%), X-ray exposure history (20.47%), and chemical hazards exposure history (17.37%). The fail-safe number showed the results were generally reliable. Conclusion In order to prevent and control children leukemia, positive and effective measures should be taken in the following aspects: strengthening child care, avoiding unnecessary X-ray exposure, and providing good living environment.
Objective To systematically evaluate the effectiveness of dasatinib in doses of 140 mg once daily and 70 mg twice daily for chronic myeloid leukemia (CML). Methods The randomized controlled trials (RCTs) were retrieved from Embase (1974 to November 2011), Pubmed (1966 to November 2011), The Cochrane Library (Issue 11, 2011), CBM (1979 to November 2011), VIP (1989 to November 2011), CNKI (1994 to November 2011), Wanfang Data (1997 to November 2011) and references listed in all articles. RCTs meeting inclusive criteria were included, the data were extracted, the quality was evaluated and cross-checked by two reviewers independently according to Cochrane Handbook for Systematic Reviews of Interventions, and then meta-analyses were conducted using RevMan 5.1 software. Results A total of four studies involving two RCTs and 862 patients were included. Results of meta-analyses showed that when dasatinib was used in the long-term treatment of CML, no significant difference was found between 140 mg once daily and 70 mg twice daily in the complete hematologic response (RR=0.97, 95%CI 0.88 to 1.07, P=0.58), complete cytogenetic response (RR=0.94, 95%CI 0.80 to 1.11, P=0.47) and major cytogenetic response (RR=0.99, 95%CI 0.86 to 1.13, P=0.86). In the short-term treatment of CML, there were no significant differences in the complete hematologic response (RR=0.99, 95%CI 0.90 to 1.07, P=0.73), complete cytogenetic response (RR=0.99, 95%CI 0.78 to 1.26, P=0.95) and major cytogenetic response (RR=1.01, 95%CI 0.83 to 1.22, P=0.95). The subgroup analyses on the long-term treatment of CML in both chronic phase and advanced phase showed that there were no significant differences in the complete hematologic response, major cytogenetic response and complete cytogenetic response. Conclusion In the effectiveness of dasatinib for CML, the dose of 140 mg once daily is similar to the dose of 70 mg twice daily. Considering possible moderate selection bias existing in the methodological quality of the included studies which may affect the authenticity of outcomes, this conclusion should be further proved by conducting more high-quality, large-scale and double- blinded RCTs.
Objective To assess the clinical effectiveness and safety of fludarabine and cyclophosphamide (FC) combined with rituximab chemotherapy regimen (FCR regimen) for patients with chronic lymphoblastic leukemia (CLL). Methods The databases such as PubMed, The Cochrane Library, SpringerLink, CNKI, and CBM were searched from 2000 to 2011. The randomized controlled trials (RCTs) on FC regimen versus FCR regimen for CLL were retrieved. The methodological quality of the included studies was assessed according to the Cochrane Reviewer’s Handbook, and meta-analyses were performed using RevMan 5.0 software. Results Three RCTs involving 1 623 patients with CLL were included. The results of meta-analyses showed that significant differences were found in the progression-free survival (PSF)(Plt;0.001), overall response (OR=1.94, 95%CI 1.49 to 2.53, Plt;0.000 01), complete remission (OR=2.54, 95%CI 2.00 to 3.22, Plt;0.000 01), and grade III or IV neutropenia (OR=1.60, 95%CI 1.33 to 1.92, Plt;0.000 01); but no significant differences were found in the partial response (OR=0.74, 95%CI 0.35 to 1.55, P=0.43), grade III or IV thrombocytopenia (OR=0.97, 95%CI 0.74 to 1.27, P=0.83) and autoimmune hemolytic anemia (OR=0.86, 95%CI 0.59 to 1.27, P=0.45) between FCR and FC regimen. Conclusion The FCR regimen can improve the progression-free survival, overall response and complete remission. Meanwhile, it sometimes increases the incidence of Grade III or IV events, such as neutropenia, thrombocytopenia, autoimmune hemolytic anemia and nausea and vomiting.
Objective To apply the evidence-based treatment method to direct the clinical therapy of refractory chronic lymphocytic leukemia (CLL). Methods Such evidence-based medicine databases as The Cochrane Library (Issue 10, 2010), OVID database, PubMed (January 1992 to October 2010) and http://www.nccn.org/ were searched to find the clinical evidence with high quality and the optimum treatment was designed based on the patient’s preferences. Results Two RCTs and five CCTs were included. The available clinical evidence displayed that rituximab could improve the therapeutic effect of combined chemotherapy on the refractory CLL, the COP/CHOP regimens were effective for the fludarabine-resistant CLL, and hematopoietic stem cell transplantation could be an effective salvage therapy for the relapsed/refractory CLL, but not the first-line recommendation drug. This patient was treated by CHOP regimen combined with rituximab, the condition of disease was improved two months after stopping chemotherapy, and the follow-up was conducted. Conclusion Current evidence reveals that rituximab combined with CHOP regimen produces good tolerance with a better clinical outcome than that of CHOP regimen. Clinical practice results display that the combination of rituximab and CHOP regimen can bring good prognosis to the patient, but still needs high-quality evidence to prove．
Objective To investigate the expression of Bcl-2 in acute leukemia of different pathological states and its relationship with chemotherapeutic efficacy. Methods Case-control studies and cohort studies were collected by searching the electronic bibliographic databases such as CBMdisc (1979 to 2010), Chinese Sic-tech Periodical Full-text Database (1989 to 2010), WanFang (1982 to 2010), Chinese Journals Full-text Database (since 1994), China Master’s Theses Full-text Database (since 1999), and China Doctor Dissertations Full-text Database (since 1999). All the relevant studies were identified and the quality of the included studies was assessed. The RevMan 5.0 software was used for meta-analysis. Results A total of 10 studies were included. The results of meta analyses showed: the complete remission of acute leukemia with Bcl-2 positivity was lower than that of the Bcl-2 negative patients after chemotherapy and the difference between them was significant (OR=0.26, 95%CI 0.14 to 0.46); the difference between acute lymphocytic leukemia and acute non-lymphocytic leukemia in terms of Bcl-2 positive rate was not significant (OR=0.87, 95%CI 0.46 to 1.65); the Bcl-2 positive rate in complete remission (CR) patients after chemotherapy was significantly lower than that of partial remission (PR) and none remission (NR) patients (SMD= –0.87, 95%CI –1.53 to –0.20, P=0.01). Conclution The current domestic evidence proves that Bcl-2 is significantly correlated with the remission rate of acute leukemia patients, but more high-quality studies are still needed.
Objective To assess the clinical effectiveness and safety of granulocyte colony stimulating factor (G-CSF) for patients with acute lymphoblastic leukemia (ALL). Methods We searched the Cochrane Library, PubMed, EMbase, CNKI, and VIP databases from January 2000 to October 2009. Randomized controlled trials (RCTs) about G-CSF for patients with ALL were retrieved. The methodological quality of the included studies was assessed and the data was extracted according the Cochrane Reviewer’s Handbook. Meta-analyses for overall survival, complete remission, quality of life, infections, relapse rate, and adverse events were performed using RevMan 5.0 software. Results Six RCTs involving 620 patients with ALL were included. The results of meta-analyses showed that the G-CFS group was superior to the control group in the overall survival of adult ALL patients (RR=2.24, 95%CI 1.28 to 3.90, P=0.004). Conclusion G-CSF can improve the overall survival of adult ALL patients. However, it is not demonstrated that G-CSF could improve complete remission rate and quality of life, and reduce infections and relapse rate. More high-quality and large scale RCTs are required.