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 systematically review the pharmacoeconomic evaluation related to relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), and to summarize its model structure, parameter inclusion and other methodological parts for future r/r B-ALL-related interventions, and to provide references for conducting pharmacoeconomic evaluations. Methods PubMed, EMbase, The Cochrane Library, CNKI and WanFang Data databases were electronically searched to collect relevant literature on the pharmacoeconomic evaluation model of r/r B-ALL from inception to August 6th, 2021. Two reviewers independently screened literature, extracted data, and assessed the quality of the included studies. The data on the model structure, methods, and parameter inclusion were then summarized. Results A total of 10 studies using different modeling methods were included. Due to the lack of head-to-head trials, most of the efficacy parameters for the intervention and control groups were derived from different clinical trials and compared indirectly. All studies used quality-adjusted life years (QALYs) as output indicators, and some used life years (LYs) as output indicators and reported the incremental cost effectiveness ratio (ICER). All studies measured the cost of treatment and hematopoietic stem cell transplantation; a few studies also conducted subgroup analysis. Conclusion The number of studies on the economic evaluation of r/r B-ALL is relatively small, and there are large differences in model types, health status, and parameter inclusion. It is suggested that researchers should guarantee the integrity of the report format and normative according to available data choice drug economics evaluation model and establish the reasonable hypothesis under the condition of the patient population heterogeneity uncertainty, perform subgroup analysis especially on the subgroup which did not receive salvage therapy. In the absence of head-to-head clinical trials, appropriate indirect comparison methods are adopted according to the data obtained to reduce methodological differences and improve the quality of relevant pharmacoeconomic research in China.
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.
Chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) is a malignancy of mature B cells characterized by progressive lymphocytosis, lymphadenopathy, and splenomegaly. On February 21st 2019, with the accumulating of new data, the National Comprehensive Cancer Network updated the guideline for CLL/SLL. This article aims at providing a reasonable interpretation of the most important messages conveyed in the guideline.
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.
Objective To explore the prognostic value of red cell volume distribution width (RDW) for hematological malignancies. Methods PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang, Chongqing VIP, and SinoMed were searched for related literatures on myelodysplastic syndrome, leukemia and other hematological malignancies and pretreatment RDW from the establishment of databases to April 5, 2022. The main statistical indicators were Hazard ratio (HR) and its 95% confidence interval (CI). Stata 12.0 SE software was used for analysis, and Q test was used to evaluate literature heterogeneity. Subgroup pooled analysis was used to evaluate the prognostic value of RDW. Results A total of 7 articles were included, with a total of 804 patients. A fixed-effect model was selected for meta-analysis, and the results showed that patients with elevated pretreatment RDW had worse overall survival [HR=2.91, 95%CI (2.01, 4.22), I2=0%, P=0.714]. The results of subgroup analysis for different types of diseases showed that in myelodysplastic syndrome group [HR=2.61, 95%CI (1.28, 5.31), I2=22.0%, P=0.258)], chronic myeloid leukemia group [HR= 3.24, 95%CI (1.91, 5.51), I2=0%, P=0.546], and adult T-cell leukemia/lymphoma group [HR=2.64, 95%CI (1.22, 5.70)], the overall survival rate of patients with elevated pretreatment RDW were worse. Sensitivity analysis showed that the study was stable and there was no heterogeneity in the overall study result.Conclusion Elevated pretreatment RDW is associated with overall survival and can be used as an indicator for evaluating the prognosis of hematological malignancies, but large sample studies are still needed to determine the best predictive cutoff for various diseases.
Mitochondrial quality control includes mechanisms such as mitochondria-derived vesicles, fusion / fission and autophagy. These processes rely on the collaboration of a variety of key proteins in the inner and outer membranes of mitochondria to jointly regulate the morphological structure and functional integrity of mitochondria, repair mitochondrial damage, and maintain the homeostasis of their internal environment. The imbalance of mitochondrial quality control is associated with leukemia. Therefore, by exploring the mechanisms related to mitochondrial quality control of various leukemia cells and their interactions with immune cells and immune microenvironment, this article sought possible targets in the treatment of leukemia, providing new ideas for the immunotherapy of leukemia.
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 investigate the expression levels of fatty acid metabolism-related genes in acute myeloid leukemia (AML) and construct a prognostic risk regression model for AML. Methods Gene expression data from control groups and AML patients were downloaded from the GTEx database and The Cancer Genome Atlas (TCGA) database, followed by screening for differentially expressed genes (DEGs) between AML patients and controls. Fatty acid metabolism-related genes were obtained from the MSigDB database. The intersection of DEGs and fatty acid metabolism-related genes yielded fatty acid metabolism-associated DEGs. A protein-protein interaction network was constructed using the STRING database. Hub genes were analyzed via random forest, Kaplan-Meier survival, and Cox proportional hazards regression based on TCGA clinical data to establish a prognostic model and evaluate their diagnostic and prognostic significance. Immune cell infiltration differences between high- and low-risk groups were assessed using CIBERSORT algorithms to explore immune microenvironment variations and correlations with risk scores. Results A total of 60 fatty acid metabolism-related DEGs were identified. Further screening revealed 15 hub genes, among which four genes (HPGDS, CYP4F2, ACSL1, and EHHADH) were selected via integrated random forest, Cox regression, and Kaplan-Meier analyses to construct an AML prognostic lipid metabolism gene signature. Heatmaps demonstrated statistically significant differences in tumor-infiltrating immune cell proportions between risk groups (P<0.05). Conclusion The constructed lipid metabolism gene prognostic model may serve as a biomarker for overall survival in AML patients and provide new insights for immunotherapy drug development.
Continuous activation of Janus kinase (JAK)- signal transduction and activator of transcription (STAT) signaling pathway is prevalent in leukemia cells, and it has been found that this pathway plays an important role in acute leukemia (AL). JAK2/JAK1 gene mutations are found in both acute myelocytic leukemia and acute lymphoblastic leukemia and may have implications for the treatment and overall prognosis of the disease. Among the STAT family members, STAT3 and STAT5 proved to be key factors in AL. These gene mutations may provide new targets and new ideas for the treatment of AL. This article provides a review of the research progress of JAK-STAT signaling pathway, related gene mutations and AL.