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Bone Marrow Transplantation Feb 2023The optimal myeloablative conditioning (MAC) regimens in adult patients with acute myeloid leukemia (AML) undergoing allogeneic hemopoietic stem cell transplantation... (Meta-Analysis)
Meta-Analysis
Myeloablative conditioning regimens in adult patients with acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation in complete remission: a systematic review and network meta-analysis.
The optimal myeloablative conditioning (MAC) regimens in adult patients with acute myeloid leukemia (AML) undergoing allogeneic hemopoietic stem cell transplantation (allo-HSCT) in complete remission (CR) remain unclear. We performed a systematic review and network meta-analysis to compare the effects of different MAC regimens. Bayesian network meta-analysis was performed using WinBUGS version 1.4.3. The commonly used MAC regimen Bu/Cy (4-day busulfan for toal 16 mg/kg orally or 12.8 mg/kg intravenously, plus 2-day cyclophosphamide for toal 120 mg/kg intravenously) is chosen as the common comparator. Pooled hazard ratios (HRs) with the associated 95% credibility interval (95% CrI) are obtained for all comparisons. We included 19 eligible studies, involving 8104 AML patients and 9 MAC regimens. Compared with Bu/Cy, 3-day busulfan plus fludarabine and thiotepa (Bu3/Flu/TT) is associated with significantly better overall survival (HR, 0.70; 95% CrI, 0.51 to 0.96) and lower risk of relapse (HR, 0.59; 95% CrI, 0.35 to 0.98). Bu3/Flu/TT is also associated with superior overall survival than Cy/TBI (cyclophosphamide plus total body irradiation), and lower risk of relapse than Bu4/Flu (4-day busulfan plus fludarabine). These results suggest that thiotepa-based new MAC regimen Bu3/Flu/TT is associated with improved outcomes in AML patients undergoing allo-HSCT in CR and worth further investigation.
Topics: Humans; Adult; Busulfan; Thiotepa; Bayes Theorem; Network Meta-Analysis; Transplantation, Homologous; Graft vs Host Disease; Leukemia, Myeloid, Acute; Hematopoietic Stem Cell Transplantation; Cyclophosphamide; Recurrence; Retrospective Studies; Transplantation Conditioning
PubMed: 36357773
DOI: 10.1038/s41409-022-01865-6 -
Frontiers in Pharmacology 2021Off-target effects in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs) are associated with cardiovascular toxicity. Hypertension...
Off-target effects in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs) are associated with cardiovascular toxicity. Hypertension represents an important cardiovascular complication and, if not appropriately managed, can contribute to developing thrombotic events. Third-generation TKI ponatinib is associated with hypertension development, and its use is more restricted than in the past. Few data are reported for second-generation TKI, nilotinib, dasatinib, and bosutinib. The aim of this article was to evaluate with a systematic review and meta-analysis the real incidence of hypertension in CML patients treated with second- or third-generation TKI. The PubMed database, Web of Science, Scopus, and ClinicalTrials.gov were systematically searched for studies published between January 1, 2000, and January 30, 2021; the following terms were entered in the database queries: Cardiovascular, Chronic Myeloid Leukemia, CML, Tyrosine kinases inhibitor, TKI, and Hypertension. The study was carried out according to the Preferred Reporting Items for Systematic and Meta-Analyses (PRISMA) statement. A pooled analysis of hypertension incidence was 10% for all new-generation TKI, with an even higher prevalence with ponatinib (17%). The comparison with the first-generation imatinib confirmed that nilotinib was associated with a significantly increased risk of hypertension (RR 2; 95% CI; 1.39-2.88, I=0%, z=3.73, p=0.0002). The greatest risk was found with ponatinib (RR 9.21; 95% CI; 2.86-29.66, z=3.72, p=0.0002). Hypertension is a common cardiovascular complication in CML patients treated with second- or third-generation TKI.
PubMed: 34630076
DOI: 10.3389/fphar.2021.674748 -
Systematic Reviews May 2020Vascular endothelial growth factor (VEGF) is one of the angiogenesis regulators, which plays an important role in tumor angiogenesis and tumor progression. Current... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vascular endothelial growth factor (VEGF) is one of the angiogenesis regulators, which plays an important role in tumor angiogenesis and tumor progression. Current studies have found that VEGF plays an important role in hematologic diseases including acute myeloid leukemia (AML). However, the circulating levels of VEGF in AML were still controversial among published studies.
METHODS
Three databases including PubMed, EMBASE, and Cochrane Library databases were searched up to February 2020. All articles included in the meta-analysis met our inclusion and exclusion criteria. Studies will be screened and data extracted by two independent investigators. The Newcastle-Ottawa Scale (NOS) and the Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool were applied to evaluate the quality of the included studies. A random-effects model was applied to pool the standardized mean difference (SMD). Heterogeneity test was performed by the Q statistic and quantified using I. All statistical analysis was conducted in Stata 12.0 software.
RESULTS
Fourteen case-control studies were finally included in this systematic review and meta-analysis. Heterogeneity was high in our included studies (I = 91.1%, P < 0.001). Sensitivity analysis showed no significant change when any one study was excluded using random-effect methods (P > 0.05). Egger's linear regression test showed that no publication bias existed (P > 0.05). Patients with AML, mainly those newly diagnosed and untreated, have higher VEGF levels (SMD = 0.85, 95% CI 0.28-1.42). Moreover, AML patients in n ≥ 40 group, plasma group, Asia and Africa group, and age ≥ 45 group had higher circulating VEGF levels (all P < 0.05).
CONCLUSIONS
Compared to healthy controls, our meta-analysis shows a significantly higher level of circulating VEGF in AML patients, and it is associated with sample size, sample type, region, and age.
Topics: Africa; Asia; Humans; Leukemia, Myeloid, Acute; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
PubMed: 32375879
DOI: 10.1186/s13643-020-01368-9 -
Frontiers in Oncology 2022This is a systematic review and meta-analysis evaluating the prognostic significance of epigenetic mutations on the overall survival (OS) in Acute Myeloid Leukemia...
This is a systematic review and meta-analysis evaluating the prognostic significance of epigenetic mutations on the overall survival (OS) in Acute Myeloid Leukemia (AML). We searched for studies evaluating epigenetic mutations in AML (up to November 2018) in PubMed, Trip database and Cochrane library. Hazard ratio (HR) of outcomes were extracted, and random-effects model was used to pool the results. A total of 10,002 citations were retrieved from the search strategy; 42 articles were identified for the meta-analysis (ASXL1 = 7, TET2 = 8, DNMT3A = 12, IDH =15), with fair to good-quality studies. The pooled HR was 1.88 (95% CI: 1.49-2.36) for ASXL1 mutation, 1.39 (95% CI: 1.18-1.63) for TET2 mutation, 1.35 (95% CI 1.16-1.56) for DNMT3a and 1.54 (95% CI: 1.15-2.06) for IDH mutation. However, there was a substantial heterogeneity in the DNMT3a and IDH studies. In conclusion epigenetic mutations in ASXL1, TET2, DNMT3a and IDH adversely impact OS in patients with AML albeit with considerable heterogeneity and possibly publication bias. Further studies are required to address these limitations.
PubMed: 36518313
DOI: 10.3389/fonc.2022.967657 -
International Journal of... Oct 2020: The aim of this review was to evaluate the influence of aberrant phenotypes in prognosis and survival in acute myeloid leukemia (AML) patients by multiparametric flow... (Review)
Review
: The aim of this review was to evaluate the influence of aberrant phenotypes in prognosis and survival in acute myeloid leukemia (AML) patients by multiparametric flow cytometry. : Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a review of PubMed, Scopus, Science Direct and Web of Science was carried out through 1998 to 2016, conducted by two reviewers independently, evaluating titles, abstracts and full-texts of the selected studies. : Ten studies were included on this review, in which the aberrant phenotype expression of 17 markers were detected in AML patients. From these, 11 aberrant phenotypes were associated with prognosis, which eight had shown negative impact on prognosis: CD7, CD56, CD15, CD2, CD3, CD90, CD123, CD117, and three others were associated with good prognosis: CD19, CD98 and CD117/CD15. Meta-analysis showed that aberrant expression of CD56 as a poor prognostic marker with unfavorable outcomes is implicated in decreased overall survival in AML patients in 28 months (95% CI: 0.62 to 0.92). This was observed when there was association between CD56 expression and other prognostic factors, influencing on patients' management care and treatment.
PubMed: 33603989
DOI: 10.18502/ijhoscr.v14i4.4484 -
Farmacia Hospitalaria : Organo Oficial... 2023Several studies quantitatively described patients with Chronic Myeloid Leukemia on active treatment with tyrosine kinase inhibitors, however there are few qualitative... (Review)
Review
OBJECTIVE
Several studies quantitatively described patients with Chronic Myeloid Leukemia on active treatment with tyrosine kinase inhibitors, however there are few qualitative studies that focus their results on how to accompany patients in the course of the disease over time. The objective of this review is to find out what are the expectations, information needs and experiences that determine adherence to treatment with tyrosine kinase inhibitors in patients with Chronic Myeloid Leukemia in qualitative research articles published in the scientific literature.
METHODS
A systematic review of qualitative research articles published between 2003-2021 was carried out in PubMed/Medline, Web of Science and Embase databases. Main keywords used were: "Leukemia, Myeloid" and "Qualitative Research". Articles on the acute phase or blast phase were excluded.
RESULTS
184 publications were located. After elimination of duplicates, 6 (3%) were included and 176 (97%) publications were excluded. Studies show that the illness is a turning point in patients' lives, and they develop their own strategies for managing the adverse effects. The factors that determine medication experiences with tyrosine kinase inhibitors should be addressed by implementing personalized strategies: this would result in early detection of problems, reinforce education at each stage and promote open discussion about complex causes underlying the treatment failure.
CONCLUSIONS
This systematic review provides evidence that implementation personalized strategies must be done to adress the factors that determine the illness experience with Chronic Myeloid Leukemia and receiving treatment with tyrosine kinase inhibitors.
Topics: Humans; Antineoplastic Agents; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Drug-Related Side Effects and Adverse Reactions; Fusion Proteins, bcr-abl
PubMed: 36870818
DOI: 10.1016/j.farma.2023.02.002 -
Frontiers in Oncology 2022Chronic myeloid leukaemia is blood cancer due to a reciprocal translocation, resulting in a BCR-ABL1 oncogene. Although tyrosine kinase inhibitors have been successfully...
Chronic myeloid leukaemia is blood cancer due to a reciprocal translocation, resulting in a BCR-ABL1 oncogene. Although tyrosine kinase inhibitors have been successfully used to treat CML, there are still cases of resistance. The resistance occurred mainly due to the mutation in the tyrosine kinase domain of the BCR-ABL1 gene. However, there are still many cases with unknown causes of resistance as the etiopathology of CML are not fully understood. Thus, it is crucial to figure out the complete pathogenesis of CML, and miRNA can be one of the essential pathogeneses. The objective of this study was to systematically review the literature on miRNAs that were differentially expressed in CML cases. Their target genes and downstream genes were also explored. An electronic search was performed PubMed, Scopus, EBSCOhost MEDLINE, and Science Direct. The following MeSH (Medical Subject Heading) terms were used: chronic myeloid leukaemia, genes and microRNAs in the title or abstract. From 806 studies retrieved from the search, only clinical studies with experimental evidence on the target genes of the studied miRNAs in CML cells were included. Two independent reviewers independently scrutinised the titles and abstracts before examining the eligibility of studies that met the inclusion criteria. Study design, sample size, sampling type, and the molecular method used were identified for each study. The pooled miRNAs were analysed using DIANA tools, and target genes were analysed with DAVID, STRING and Cytoscape MCODE. Fourteen original research articles on miRNAs in CML were included, 26 validated downstream genes and 187 predicted target genes were analysed and clustered into 7 clusters. Through GO analysis, miRNAs' target genes were localised throughout the cells, including the extracellular region, cytosol, and nucleus. Those genes are involved in various pathways that regulate genomic instability, proliferation, apoptosis, cell cycle, differentiation, and migration of CML cells.
PubMed: 35330714
DOI: 10.3389/fonc.2022.848199 -
Expert Review of Anticancer Therapy 2023Studies have shown that myeloma cell leukemia-1 (MCL-1) is associated with the prognosis of patients with cancer. To further validate the prognostic value of MCL-1 in... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Studies have shown that myeloma cell leukemia-1 (MCL-1) is associated with the prognosis of patients with cancer. To further validate the prognostic value of MCL-1 in cancer, a meta-analysis was conducted.
METHODS
Six databases were searched using Boolean logic search formulas. Data were extracted from the included literature, and pooled odds ratio, hazard ratio, and 95% confidence interval were calculated to determine the relationship between MCL-1 levels and clinicopathological characteristics and prognosis of patients with cancer. When heterogeneity was found to be significant, a random effects model was used, otherwise, a fixed effects model was used.
RESULTS
Twelve articles were included in this meta-analysis, totaling 2208 patients with cancer across 14 studies. A high MCL-1 expression level was associated with patients with high T stage, M stage, and TNM stage in some cancers. Additionally, high MCL-1 expression was likely to be observed in patients with poorly differentiated digestive system tumors and patients with lung adenocarcinoma. Notably, a higher expression of MCL-1 was found to be associated with shorter overall survival in patients with hematological tumors, digestive system tumors, and lung cancer.
CONCLUSION
MCL-1 may be a prognostic biomarker in patients with some types of cancer.
Topics: Humans; Biomarkers, Tumor; Digestive System Neoplasms; Leukemia; Myeloid Cell Leukemia Sequence 1 Protein; Myeloid Cells; Prognosis
PubMed: 37467344
DOI: 10.1080/14737140.2023.2238900 -
Patient Preference and Adherence 2021Suboptimal adherence to tyrosine kinase inhibitors (TKIs) is a widely recognized issue compromising the disease control and survival of patients with chronic myeloid... (Review)
Review
PURPOSE
Suboptimal adherence to tyrosine kinase inhibitors (TKIs) is a widely recognized issue compromising the disease control and survival of patients with chronic myeloid leukemia (CML). A recently published review by Heiney et al reported inconclusive findings on the effects of a broad range of adherence enhancing interventions. The current systematic review aimed to identify studies that evaluated adherence-enhancing interventions implemented by healthcare professionals and determine their effect on CML patients' medication adherence and clinical outcomes.
METHODS
A systematic literature search was performed in 5 databases for articles published between 2002 and 2021. Studies that compared adherence enhancing interventions implemented by healthcare professionals with a comparison group were included. Relevant data on study characteristics were extracted. Medication adherence and clinical outcomes between intervention and control arms were compared.
RESULTS
Nine studies were included in two randomised controlled trials, four cohort studies, and three before-and-after comparison studies. All the included studies incorporated complex interventions, including intensive education or consultation with pharmacists, nurses or multidisciplinary team, in combination with one or more other strategies such as structured follow-up, written materials or video, psychotherapy, medication reminder or treatment diary, with the overall goal of monitoring and improving TKI adherence. Most (7 out of 9) studies demonstrated significantly better adherence to TKIs in the intervention group than the comparison group. The relative proportion of participants who adhered to TKIs ranged from 1.22 to 2.42. The improvement in the rate of TKI doses taken/received ranged from 1.5% to 7.1%. Only one study showed a significant association between intervention and clinical outcomes, with a 22.6% higher major molecular response rate and improvement in 6 out of 20 subscales of health-related quality-of-life.
CONCLUSION
Complex interventions delivered by healthcare professionals showed improvement in adherence to TKIs in CML patients. Further studies are required to clarify the cost-effectiveness of adherence-enhancing interventions.
PubMed: 34819724
DOI: 10.2147/PPA.S269355 -
American Journal of Translational... 2023To systematically assess the efficacy of hematopoietic stem cell transplantation (HSCT) and bone marrow transplantation (BMT) in treating acute myeloid leukemia (AML). (Review)
Review
OBJECTIVE
To systematically assess the efficacy of hematopoietic stem cell transplantation (HSCT) and bone marrow transplantation (BMT) in treating acute myeloid leukemia (AML).
METHODS
PubMed, EMBASE, ScienceDirect, Cochrane Library, China National Knowledge Infrastructure (CNKI), China VIP database, Wanfang database and China Biomedical Literature Database (CBM) were searched for case-control trials of bone marrow HSCT and peripheral HSCT (PHSCT) for treating AML. Two independent researchers extracted the data between January 2000 and May 2022. Each retrieved article was assessed according to the bias risk defined in Cochrane Handbook 5.3, and data were analyzed by meta-analysis using RevMan5.3.
RESULTS
Through computer database retrieval, 7 clinical controlled studies were included, with 1280 samples. A meta-analysis was conducted on the survival rates. The PHSCT and the BMT groups showed no noticeable difference in overall survival (OS) and disease-free survival (DFS) rates (P>0.05). The incidence of acute graft-versus-host disease (GVHD) and chronic GVHD in the BMT group was noticeably lower (P<0.05). The disease recurrence rate in tthe BMT group was lower (P<0.05), but no noticeable differences were found in recurrence-related mortality (P>0.05). Furthermore, there was also no noticeable difference in non-relapse-related mortality (P>0.05). Funnel charts were drawn on the basis of OS rate, DFS rate, incidences of acute GVHD and chronic GVHD, and recurrence. Afterwards publication bias analysis was carried out. Symmetry presented in the majority of the funnel charts and asymmetry was seen in a few, suggesting possible publication bias in the selected literature because of the small sample and the heterogeneity.
CONCLUSION
BMT can be used as an effective treatment for patients with AML, because it can reduce the recurrence rate and the incidence of complications while ensuring a curative effect, suggesting that BMT is worth popularizing in the clinic. Longer follow-up studies are needed to provide more support for the clinical application of BMT in AML patients.
PubMed: 36777836
DOI: No ID Found