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 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.
ObjectiveTo explore the risk factors of nosocomial infection in children with acute lymphoblastic leukemia during induction remission chemotherapy.MethodsThe children with acute lymphoblastic leukemia who were admitted to the Department of Pediatrics, Huai’an First Hospital Affiliated to Nanjing Medical University between December 2012 and December 2018 were divided into the infection group (including the severe infection subgroup and the non-severe infection subgroup) and the non-infection group according to whether nosocomial infection occurred during induction and remission chemotherapy. The clinical data of patients were collected. Univariate analysis and multivariate logistic regression were used to analyze the risk factors of nosocomial infection during induction remission chemotherapy in children with acute lymphoblastic leukemia.ResultsA total of 96 patients were included. There were 67 cases in the infection group (26 in the severe infection subgroup and 41 in the non-severe infection subgroup) and 29 cases in the non-infection group. Univariate analysis showed that the granulocyte deficiency time and the prevalence of skin and mucosal damage in the infection group were significantly higher than those in the non-infection group, and the infection group had significantly lower laminar bed use and serum albumin level than the non-infection group did (P< 0.05). Multivariate logistic regression analysis showed that prolonged agranulocytosis [odds ratio (OR)=23.075, 95% confidence interval (CI) (3.682, 144.617), P=0.001], skin and mucosal lesions [OR=12.376, 95%CI (1.211, 126.507), P=0.034], hypoalbuminemia [OR=5.249, 95%CI (1.246, 22.113), P=0.024] were independent risk factors for nosocomial infection during induction and remission of childhood acute lymphoblastic leukemia, while laminar bed [OR=0.268, 95%CI (0.084, 0.854), P=0.026] was the protective factor.ConclusionsLong-term agranulocytosis, skin and mucosal lesions, and hypoalbuminemia are independent risk factors for nosocomial infection in children with acute lymphoblastic leukemia during induction remission chemotherapy. Laminar flow bed is its protective factor.
ObjectiveTo explore the clinical features and outcomes of relapsed acute lymphoblastic leukemia (ALL) in children. MethodsThirty-two ALL children treated in line with the Chinese Child Leukemia Cooperative Group ALL-2008 protocol with a relapse of the disease during January 2009 to May 2013 were enrolled into this study. Their clinical features and outcomes were retrospectively analyzed and compared with those who achieved continuous complete remission (CCR). ResultsThere were 32 relapsed cases among 319 newly diagnosed ALL cases (excluding infantile ALL) during the study period, with a relapse rate of 10%. In the relapse group, the proportions of patients with peripheral blood white blood cell count ≥50×109/L at diagnosis, positive BCR/ABL fusion gene, poor prednisone response, high risk stratification, and who failed to achieve bone marrow complete remission at d15 and d33 of induction chemotherapy, were significantly higher than those in the CCR group (all P<0.05). Multivariate analysis showed that high risk stratification was an independent risk factor for relapse (OR=3.529, P=0.002). In terms of site of relapse, isolated marrow relapse, isolated central nervous system relapse, isolated testicular relapse and combined relapse accounted for 23 (72%), 6 (19%), 1 (3%) and 2 (6%), respectively. As regard to the time of relapse, 26 cases (81%), 4 cases (13%) and 2 cases (6%) were categorized as very early relapse, early relapse and late relapse respectively. Twenty-four children with relapsed ALL received re-induction chemotherapy. Among them, 16 cases (67%) achieved second complete remission. Nevertheless, 9 cases ultimately suffered second relapse. ConclusionRelapse, which occurs more commonly in high risk ALL group, still remains a great challenge in clinical practice. Relapsed ALL, especially those with very early and early marrow relapse, has poor prognosis.
The poor treatment effect and short survival period of patients with acute leukemia are mainly due to the lack of effective early diagnosis and treatment targets. Lipid metabolism reprogramming meets the material and energy requirements for rapid proliferation and division of tumor cells, and is associated with the invasiveness, recurrence, and chemotherapy resistance of acute leukemia. This article reviews the carcinogenic and chemotherapy resistance mechanisms of lipid metabolism reprogramming in leukemia cells, and summarizes the latest findings on targeted fatty acid metabolism pathways, aiming to provide a new perspective on the role of intracellular fatty acid metabolism in the occurrence and development of acute leukemia. It is expected to provide a theoretical basis for the elucidation of its resistance mechanism and the development of corresponding targeted therapies.
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.
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 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.
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.
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.