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 We intended to get good understanding of the current role of imatinib （or glivec） in the treatment of a patient with chronic-phase chronic myeloid leukemia. Methods We attempted to find the current best evidence of imatinib for treating chronic myeloid leukemia in chronic phase by searching ACP Journal Club （1991 -Jun, 2005 ）, The Cochrane Library（Issue 2, 2005 ）and MEDLINE（1990 -Jun, 2005 ） and further critically appraised the available evidence. Results Imatinib appeared to be more effective than current standard drag treatments in terms of hematologic and cytogenetic response with better quality of life and fewer side effects. However, there was uncertainty concerning long term outcomes. Given the current evidence together with our clinical experience and considering the patient and his family members＇ values and preference, imatinib （400 mg qd） was administered to him. No obvious adverse effects occurred with 3 months follow-up. Conclusions Imatinib is effective and well tolerated in the treatment of chronic myeloid leukemia in chronic phase. Further researches on long-term follow-up data from imatinib trials are definitely needed.
ObjectiveTo systematically review the correlation between DNMT3a mutation and peripheral blood cell count on the time of diagnosis for adult primary acute myeloid leukemia (AML). MethodsLiterature search in the databases such as PubMed, ScienceDirect, EBSCO, Web of Science, CNKI, VIP and WanFang Data was performed to collect the case-control studies about the correlation between the DNMT3a mutations and adult AML up to December 2012. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the methodological quality of the included studies, and then RevMan 5.0 software was conducting for metaanalysis. ResultsA total of 10 studies involving 2 704 patients were included. The results of meta-analyses showed that:the levels of peripheral blood WBC, HGB and PLT of the DNMT3a-mutated group were significantly higher than those of the DNMT3a-wildtype group for the initial visit of adult primary AML patients (all P values < 0.05). ConclusionThe peripheral blood cell counts of the DNMT3a-mutated group are higher than those of the DNMT3a-wildtype group for the initial visit of adult primary AML patients, indicating DNMT3a mutation might contribute to promote cell proliferation, and this helps us better understand the role of DNMT3a mutation in the development of AML.
ObjectivesTo systematically review the risk of arterial ischemic and metabolic adverse events in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs).MethodsPubMed, EMbase, The Cochrane Library, CNKI, WanFang Data and VIP databases were searched to collect clinical trials, observational studies and case reports of adverse events in CML patients treated with TKIs from inception to February 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using Stata 12.0 software.ResultsA total of 22 studies involving 4 223 patients were included. The incidence rates of ischemic heart disease in any grade were 2 per 100 patient-years (95%CI 2 to 3) for nilotinib, and 0 per 100 patient-years (95%CI 0 to 3) for imatinib. The incidence of ischemic heart disease in grade 3 or 4 was 1 per 100 patient-years (95%CI 0 to 2) for nilotinib. The incidence of peripheral arterial occlusive disease in any grade was 2 per 100 patient-years (95%CI 0 to 14) for nilotinib, and 0 per 100 patient-years (95%CI 0 to 2) for imatinib. The incidence of hypertension in any grade was 1 per 100 patient-years (95%CI 0 to 3) for nilotinib, and 44 per 100 patient-years (95%CI 27 to 71) for ponatinib. The incidence of hypertension in grade 3 or 4 was 2 per 100 patient-years (95%CI 0 to 15) for nilotinib, and 22 per 100 patient-years (95%CI 8 to 58) for ponatinib. The incidence of hyperlipidemia in any grade was 17 per 100 patient-years (95%CI 5 to 59) for nilotinib. The incidence of hyperglycemia in any grade was 11 per 100 patient-years (95%CI 9 to 15) for nilotinib, 2 per 100 patient-years (95%CI 1 to 4) for imatinib, 1 per 100 patient-years (95%CI 0 to 5) for dasatinib, and 19 per 100 patient-years (95%CI 19 to 20) for bosutinib. The incidence of hyperglycemia in grade 3 or 4 was 4 per 100 patient-years (95%CI 3 to 5) for nilotinib, and 1 per 100 patient-years (95%CI 1 to 2) for bosutinib.ConclusionsPatients treated with nilotinib have a greater possibility of ischemic heart and peripheral arterial occlusive disease compared with patients treated with imatinib. Patients treated with ponatinib have a high incidence rate of hypertension, and patients treated with nilotinib have a high incidence rate of hyperlipidemia. Patients treated with bosutinib and nilotinib have higher risk of hyperglycemia compared with patients treated with imatinib or dasatinib.
ObjectiveTo analyze the clinical efficacy of decitabine contained chemotherapy regimens in the treatment of relapsed or refractory acute myeloid leukemia (AML) patients.MethodsA total of 101 patients with relapsed or refractory AML from May 2014 to December 2017 were collected retrospectively. Three schemes with a relatively larger number of users were included: 15 cases were treated with decitabine monotherapy (DAC regime); 37 cases were treated with decitabine, anthracycline antibiotic, and cytarabine (D-DA regime); and 49 cases were treated with decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulatingfactor (G-CSF) (D-CAG regimen). The remission rate, blood products support strength, degree and duration of bone marrow suppression, adverse reaction, and survival time were compared.ResultsThe complete remission (CR) rates of DAC, D-DA and D-CAG regimen group were 40.0%, 48.6%, and 71.4%, respectively; the overall respond rates (ORR) were 46.7%, 54.1%, and 79.6%, respectively. The ORR in D-CAG regimen group was higher than those in the other two groups (P<0.017). The dosage of G-CSF in D-CAG regimen group were lower than those in DAC regimen group [ (1 363.0±1 037.9) vs. (2 517.0±1 163.4) μg, P<0.05]; the mean number of erythrocyte transfusion and the dosage of G-CSF were lower than those in D-DA regimen group [(6.7±4.0) vs. (14.8±10.1) U, P<0.05; (1 363.0±1 037.9) vs. (2 786.0±1474.0) μg, P<0.05]; the time to the suppression of hemoglobin and platelet in D-CAG regimen group were later than those in D-DA regimen group [(11.5±2.6) vs. (8.8±2.5) days, P=0.007; (10.9±2.6) vs. (7.6±2.5) days, P=0.002]; the time to the suppression of platelet was later than that in DAC regimen group [(10.9±2.6) vs. (7.6±1.6) days, P=0.003]. There was no statistically significant difference in the incidence of adverse reations among the three group (P>0.05). The median overall survival of D-CAG regimen group was longer than that in DAC regimen group (11.6 vs. 8.8 months, P=0.013).ConclusionAmong the three chemotherapy regimens containing decitabine, the CR and ORR of D-CAG regimen are higher, the tolerance is better, and further promotion can be attempted in qualified medical institutions.
Mouse animal models are the most commonly used experimental tools in scientific research, which have been widely favored by researchers. The animal model of mouse leukemia appeared in the 1930s. During the past 90 years, researchers have developed various types of mouse leukemia models to simulate the development and treatment of human leukemia in order to promote effectively the elucidation of the molecular mechanism of leukemia' development and progression, as well as the development of targeted drugs for the treatment of leukemia. Considering that to myeloid leukemia, especially acute myeloid leukemia, there currently is no good clinical treatment, it is urgent to clarify its new molecular mechanism and develop new therapeutic targets. This review focuses on the various types of mouse models about myeloid leukemia used commonly in recent years, including mouse strains, myeloid leukemia cell types, and modeling methods, which are expected to provide a reference for relevant researchers to select animal models during myeloid leukemia research.
Objective To systematically review the health economic evaluation studies of medicines for the treatment of acute myeloid leukemia (AML). MethodsThe PubMed, EMbase, Cochrane Library, CBM, CNKI, and WanFang Data, as well as the CRD database specifically for health economics were electronically searched from inception to June 2022, and related journals in the field of health economics and the websites of HTA institutions in various countries were manually searched. The quality of the studies was assessed using the CHEERS checklist. The basic characteristics of health economics evaluation publications were summarized, the quality of model structures and methodologies was assessed and economic evaluation results were compared among different treatments. Results A total of 17 studies were included, and cost-effectiveness analyses were conducted from the perspectives of the health system, patients, the whole society, and medical insurance payers. The economic evaluation models were relatively unified, but there were differences in methods and results reporting, and the quality needed to be improved. The research objects were mainly the comparison of hypomethylating agents, targeted medicine and traditional chemotherapy regimens, as well as the comparison of different chemotherapy combinations and different drug dosages. Conclusion Real-world studies are mainly focused on traditional chemotherapy regimens, and model-based health economic evaluations, such as Markov models, are more frequently applied to newly developed targeted drugs and demethylation drugs. Among all treatments, the chemotherapy regimens including cytarabine, midostaurin, and decitabine are found to be more cost-effective.