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Transfusion Oct 2020Up to 20% of patients with acute myeloid leukemia (AML) present with hyperleukocytosis, usually defined as a white blood cell (WBC) count greater than 100 × 10 /L.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Up to 20% of patients with acute myeloid leukemia (AML) present with hyperleukocytosis, usually defined as a white blood cell (WBC) count greater than 100 × 10 /L. Given the high early mortality rate, emergent cytoreduction with either leukapheresis, hydroxyurea, or chemotherapy is indicated, but the optimal strategy is unknown.
STUDY DESIGN AND METHODS
For this systematic review and meta-analysis we searched MEDLINE and EMBASE via Ovid, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science from inception through March 2020 for multiarm studies comparing early mortality rates of patients with AML treated with leukapheresis and those who were not. The risk ratio (RR) of early death for patients who received leukapheresis vs patients who did not was estimated using a sum of the log-ratio of individual study estimates weighted by sample size.
RESULTS
Among 13 two-arm, retrospective studies with 1743 patients (486 leukapheresis and 1257 nonleukapheresis patients), leukapheresis did not improve the primary outcome of early mortality compared to treatment strategies in which leukapheresis was not used (RR, 0.88; 95% confidence interval [CI], 0.69-1.13; P = .321) without statistically significant heterogeneity between studies (Cochran's Q, 18; P = .115; I , 33.4%). Patients presenting with clinical leukostasis tended to be more likely to undergo leukapheresis (odds ratio, 2.01; 95% CI, 0.99-4.08; P = .052).
CONCLUSION
As we did not find evidence of a short-term mortality benefit and considering the associated complications and logistic burden, our results argue against the routine use of leukapheresis for hyperleukocytosis among patients with AML.
Topics: Disease-Free Survival; Humans; Hydroxyurea; Leukapheresis; Leukemia, Myeloid, Acute; Leukocytosis; Randomized Controlled Trials as Topic; Survival Rate
PubMed: 32776542
DOI: 10.1111/trf.15994 -
Frontiers in Immunology 2021Previous trials demonstrated evidence involving the total effects of gemtuzumab ozogamicin (GO), an anti-CD33 humanized antibody, on treating acute myeloid leukemia... (Meta-Analysis)
Meta-Analysis
Clinical Benefits and Safety of Gemtuzumab Ozogamicin in Treating Acute Myeloid Leukemia in Various Subgroups: An Updated Systematic Review, Meta-Analysis, and Network Meta-Analysis.
BACKGROUND
Previous trials demonstrated evidence involving the total effects of gemtuzumab ozogamicin (GO), an anti-CD33 humanized antibody, on treating acute myeloid leukemia (AML). In this updated systematic review, meta-analysis, and network meta-analysis (NMA), we aimed to comprehensively explore the clinical benefits and safety of GO in various subtypes of AML.
METHODS
PubMed, Embase, Cochrane, and Chinese databases were filtered to search randomized controlled trials (RCTs) and retrospective cohort studies that compared clinical efficiency and toxicity of GO with non-GO groups in AML. Random-effects models were used to calculate pooled effect sizes and 95% confidence intervals (CIs). Relative risk (RR) was used for estimating complete remission (CR), early death, and toxicity. Hazard risk (HR) was accomplished to evaluate survival.
RESULTS
Fifteen RCTs and 15 retrospective cohort studies were identified (GO: 4,768; Control: 6,466). GO tended to improve CR (RR 0.95, p = 0.084), followed by significantly improved survival (overall survival: HR 0.86, p = 0.003; event-free survival: HR 0.86, p = 0.015; relapse-free survival: HR 0.83, p = 0.001; cumulative incidence of relapse: HR 0.82, p < 0.001). GO benefits of CR and survival were evident in favorable- and intermediate-risk karyotypes (p ≤ 0.023). GO advantages were also associated with nucleophosmin 1 mutations (p ≤ 0.04), wild-type FMS-like tyrosine kinase 3 internal tandem duplication gene (p ≤ 0.03), age of <70 years (p < 0.05), AML (p ≤ 0.017), and CD33(+) (p ≤ 0.021). Both adding GO into induction therapy (p ≤ 0.011) and a lower (<6 mg/m) dose of GO (p ≤ 0.03) enhanced survival. Prognosis of combined regimens with GO was heterogeneous in both meta-analysis and NMA, with several binding strategies showing improved prognosis. Additionally, GO was related to increased risk of early death at a higher dose (≥6 mg/m) (RR 2.01, p = 0.005), hepatic-related adverse effects (RR 1.29, p = 0.02), and a tendency of higher risk for hepatic veno-occlusive disease or sinusoidal obstruction syndrome (RR 1.56, p = 0.072).
CONCLUSIONS
These data indicated therapeutic benefits and safety of GO in AML, especially in some subtypes, for which further head-to-head RCTs are warranted.
SYSTEMATIC REVIEW REGISTRATION
[PROSPERO: https://www.crd.york.ac.uk/prospero/], identifier [CRD42020158540].
Topics: Antineoplastic Agents, Immunological; Biomarkers, Tumor; Gemtuzumab; Humans; Karyotype; Leukemia, Myeloid, Acute; Molecular Targeted Therapy; Mutation; Prognosis; Sialic Acid Binding Ig-like Lectin 3; Treatment Outcome
PubMed: 34484181
DOI: 10.3389/fimmu.2021.683595 -
Caspian Journal of Internal Medicine 2024Although genetic mutations in additional sex-combs-like 1 (ASXL1) are prevalent in acute myeloid leukemia (AML), their exact impact on the AML prognosis remains... (Review)
Review
BACKGROUND
Although genetic mutations in additional sex-combs-like 1 (ASXL1) are prevalent in acute myeloid leukemia (AML), their exact impact on the AML prognosis remains uncertain. Hence, the present article was carried out to explore the prognostic importance of ASXL1 mutations in AML.
METHODS
We thoroughly searched electronic scientific databases to find eligible papers. Twenty-seven studies with an overall number of 8,953 participants were selected for the current systematic review. The hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were extracted from all studies with multivariate or univariate analysis. Pooled HRs and p-values were also calculated as a part of our work.
RESULTS
The pooled HR for OS in multivariable analysis indicated that ASXL1 significantly diminished survival in AML patients (pooled HR: 1.67; 95% CI: 1.342-2.091).
CONCLUSIONS
ASXL1 mutations may confer a poor prognosis in AML. Hence, they may be regarded as potential prognostic factors. However, more detailed studies with different ASXL1 mutations are suggested to shed light on this issue.
PubMed: 38807730
DOI: 10.22088/cjim.15.2.202 -
Environmental Health : a Global Access... Jun 2010A substantial number of epidemiologic studies have provided estimates of the relation between exposure to benzene at work and the risk of leukemia, but the results have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A substantial number of epidemiologic studies have provided estimates of the relation between exposure to benzene at work and the risk of leukemia, but the results have been heterogeneous. To bridge this gap in knowledge, we synthesized the existing epidemiologic evidence on the relation between occupational exposure to benzene and the risk of leukemia, including all types combined and the four main subgroups acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML).
METHODS
A systematic literature review was carried out using two databases 'Medline' and 'Embase' from 1950 through to July 2009. We selected articles which provided information that can be used to estimate the relation between benzene exposure and cancer risk (effect size).
RESULTS
In total 15 studies were identified in the search, providing 16 effect estimates for the main analysis. The summary effect size for any leukemia from the fixed-effects model was 1.40 (95% CI, 1.23-1.57), but the study-specific estimates were strongly heterogeneous (I2 = 56.5%, Q stat = 34.47, p = 0.003). The random-effects model yielded a summary- effect size estimate of 1.72 (95% CI, 1.37-2.17). Effect estimates from 9 studies were based on cumulative exposures. In these studies the risk of leukemia increased with a dose-response pattern with a summary-effect estimate of 1.64 (95% CI, 1.13-2.39) for low (< 40 ppm-years), 1.90 (95% CI, 1.26-2.89) for medium (40-99.9 ppm-years), and 2.62 (95% CI, 1.57-4.39) for high exposure category (> 100 ppm-years). In a meta-regression, the trend was statistically significant (P = 0.015). Use of cumulative exposure eliminated heterogeneity. The risk of AML also increased from low (1.94, 95% CI, 0.95-3.95), medium (2.32, 95% CI, 0.91-5.94) to high exposure category (3.20, 95% CI, 1.09-9.45), but the trend was not statistically significant.
CONCLUSIONS
Our study provides consistent evidence that exposure to benzene at work increases the risk of leukemia with a dose-response pattern. There was some evidence of an increased risk of AML and CLL. The meta-analysis indicated a lack of association between benzene exposure and the risk of CML.
Topics: Benzene; Humans; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Occupational Exposure; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk Factors
PubMed: 20584305
DOI: 10.1186/1476-069X-9-31 -
JAMA Network Open Jul 2021Although BCR-ABL fusion oncoprotein tyrosine kinase inhibitors (BCR-ABL TKIs) can substantially improve the survival rate of chronic myeloid leukemia (CML), they are... (Meta-Analysis)
Meta-Analysis
Comparison of Hepatotoxicity Associated With New BCR-ABL Tyrosine Kinase Inhibitors vs Imatinib Among Patients With Chronic Myeloid Leukemia: A Systematic Review and Meta-analysis.
IMPORTANCE
Although BCR-ABL fusion oncoprotein tyrosine kinase inhibitors (BCR-ABL TKIs) can substantially improve the survival rate of chronic myeloid leukemia (CML), they are clinically accompanied by severe hepatotoxicity.
OBJECTIVE
To compare the relative risk (RR) of hepatotoxicity of new-generation BCR-ABL TKIs with that of imatinib, and to provide an overall assessment of the clinical benefit.
DATA SOURCES
PubMed, Embase, Cochrane library databases, and ClinicalTrials.gov were searched for clinical trials published between January 2000 and April 2020.
STUDY SELECTION
Study selection was conducted independently by 2 investigators according to the inclusion and exclusion criteria published previously in the protocol: only randomized phase 2 or phase 3 clinical trials that compared bosutinib, dasatinib, nilotinib, or ponatinib with imatinib were included. Among the 2666 records identified, 9 studies finally fulfilled the established criteria.
DATA EXTRACTION AND SYNTHESIS
Two investigators extracted study characteristics and data independently using a standardized data extraction form. Data were extracted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. When substantial heterogeneity was observed, pooled estimates were calculated based on the random-effect model; otherwise, the fixed-effect model was used.
MAIN OUTCOMES AND MEASURES
Data extracted included study characteristics, baseline patient information, interventions and data on all-grade and high-grade (grades 3 and 4) elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, overall survival, and major molecular response (MMR). The RRs and 95% CIs were calculated using the inverse variance method.
RESULTS
Nine trials involving 3475 patients were analyzed; the median (range) age was 49 (18-91) years; 2059 (59.2%) were male patients. Increased risks were observed for each new-generation TKI except for dasatinib. Patients receiving new-generation TKIs were more likely to experience all grades of ALT elevation (pooled RR, 2.89; 95% CI, 1.78-4.69; P < .001) and grades 3 and 4 ALT elevation (pooled RR, 4.36; 95% CI, 2.00-9.50; P < .001) compared with those receiving imatinib. Patients receiving new-generation TKIs were also more likely to experience all grades of AST elevation (pooled RR, 2.20; 95% CI, 1.63-2.98; P < .001) and grades 3 and 4 AST elevation (pooled RR, 2.65; 95% CI, 1.59-4.42; P < .001) compared with those receiving imatinib. New-generation TKIs were associated with a significantly higher rate of MMR at 1 year compared with imatinib (pooled RR, 1.59; 95% CI, 1.44-1.75; P < .001). No statistical difference in overall survival at 1 year was found between new-generation TKIs and imatinib (pooled RR, 1.00; 95% CI, 1.00-1.01; P = .33).
CONCLUSIONS AND RELEVANCE
When compared to imatinib, bosutinib, nilotinib, and ponatinib had higher relative risks of hepatotoxicity. Treatment with new-generation TKIs was associated with a higher MMR rate at 1 year but not with 1-year overall survival.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alanine Transaminase; Aniline Compounds; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Dasatinib; Female; Humans; Imatinib Mesylate; Imidazoles; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Nitriles; Oncogene Proteins v-abl; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Proto-Oncogene Proteins c-bcr; Pyridazines; Pyrimidines; Quinolines; Risk; Young Adult
PubMed: 34292334
DOI: 10.1001/jamanetworkopen.2021.20165 -
Iranian Journal of Pathology 2018Acute myeloid leukemia (AML) as a distortion of blood cells involves the differ entiation of hematopoietic stem cells. Several studies established the irregular over... (Review)
Review
Acute myeloid leukemia (AML) as a distortion of blood cells involves the differ entiation of hematopoietic stem cells. Several studies established the irregular over expression of specific genes is a common finding in patients with AML. The ectopic viral integration site-1 () gene is a protooncogene subject to alternative splicing, and encodes a zincfinger protein that acts as a transcriptional regulator in early devel opment. Forced overexpression of in hematopoietic progenitors later induced a myeloid differentiation block. The current review aimed at determining the prognos tic value of expression in patients with AML in the age range of one month to fifteen years. The scientific databases including PubMed, Google Scholar, EMBASE, Scopus, and ISI published up to January 2016 were searched using the conformity keywords and a total of four articles were studied. Three articles declared higher overexpression of in patients with mixed-lineage leukemia (MLL) rearrangements. The percentage of overall survival (OS), reported in two articles, decreased in AML patients with high EVI1 expression. A study reported that the relationship between EVI1 expression and OS was negligible in cases with and without expression. Another study showed significant differences in event free survival (EFS) and OS in the group of patients with positive MLL-AF9 between + and patients. The current study revealed that high expression was not a poor prognostic factor in pediatric patients with AML. And this gene expression was mainly prognostic concomitantly by other factors such as MLL rearrangement, expression, and white blood cell (WBC) count.
PubMed: 30636951
DOI: No ID Found -
Frontiers in Immunology 2021This analysis aimed to systematically review and synthesize the existing evidence regarding the outcome of tyrosine kinase inhibitor (TKI) maintenance therapy after... (Meta-Analysis)
Meta-Analysis
This analysis aimed to systematically review and synthesize the existing evidence regarding the outcome of tyrosine kinase inhibitor (TKI) maintenance therapy after allogeneic stem-cell transplantation for patients with -ITD-mutated acute myeloid leukemia (AML). We searched publicly available databases, references lists of relevant reviews, registered trials, and relevant conference proceedings. A total of 7 studies comprising 680 patients were included. Five studies evaluated sorafenib and 2 studies evaluated midostaurin, compared with control. The incidence of relapse was significantly reduced after TKI therapy, showing an overall pooled risk ratio (RR) of 0.35 (95% confidence interval [CI], 0.23-0.51; < 0.001), with a marked 65% reduced risk for relapse. The overall pooled RR for relapse-free survival and overall survival showed significantly improved outcome after TKI maintenance therapy, being 0.48 (95% CI, 0.37-0.61; < 0.001) and 0.48 (95% CI, 0.36-0.64; < 0.001). The risk for relapse or death from any cause was reduced by 52% using TKI. No difference in outcome was seen for non-relapse mortality, and the risk for chronic or acute graft-vs. -host disease appeared to be increased, at least for sorafenib. In conclusion, post-transplant maintenance therapy with TKI was associated with significantly improved outcome in relapse and survival in patients with -ITD positive AML.
Topics: Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Mutation; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Recurrence; fms-Like Tyrosine Kinase 3
PubMed: 33790903
DOI: 10.3389/fimmu.2021.630429 -
PloS One 2022Elderly patients with acute myeloid leukemia not eligible for intensive antileukemic therapy are treated with less intensive therapies, uncertainty remains regarding... (Meta-Analysis)
Meta-Analysis
Less intensive antileukemic therapies (monotherapy and/or combination) for older adults with acute myeloid leukemia who are not candidates for intensive antileukemic therapy: A systematic review and meta-analysis.
INTRODUCTION
Elderly patients with acute myeloid leukemia not eligible for intensive antileukemic therapy are treated with less intensive therapies, uncertainty remains regarding their relative merits.
OBJECTIVES
To compare the effectiveness and safety of less intensive antileukemic therapies for older adults with newly diagnosed AML not candidates for intensive therapies.
METHODS
We included randomized controlled trials (RCTs) and non-randomized studies (NRS) comparing less intensive therapies in adults over 55 years with newly diagnosed AML. We searched MEDLINE and EMBASE from inception to August 2021. We assessed risk of bias of RCTs with a modified Cochrane Risk of Bias tool, and NRS with the Non-Randomized Studies of Interventions tool (ROBINS-I). We calculated pooled hazard ratios (HRs), risk ratios (RRs), mean differences (MD) and their 95% confidence intervals (CIs) using a random-effects pairwise meta-analyses and assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.
RESULTS
We included 27 studies (17 RCTs, 10 NRS; n = 5,698), which reported 9 comparisons. Patients were treated with azacitidine, decitabine, and low-dose cytarabine (LDAC), as monotherapies or in combination with other agents. Moderate certainty of evidence suggests no convincing difference in overall survival of patients who receive azacitidine monotherapy compared to LDAC monotherapy (HR 0.69; 95% CI, 0.31-1.53), fewer febrile neutropenia events occurred between azacitidine monotherapy to azacitidine combination (RR 0.45; 95% CI, 0.31-0.65), and, fewer neutropenia events occurred between LDAC monotherapy to decitabine monotherapy (RR 0.62; 95% CI 0.44-0.86). All other comparisons and outcomes had low or very low certainty of evidence.
CONCLUSION
There is no convincing superiority in OS when comparing less intensive therapies. Azacitidine monotherapy is likely to have fewer adverse events than azacitidine combination (febrile neutropenia), and LDAC monotherapy is likely to have fewer adverse events than decitabine monotherapy (neutropenia).
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Humans; Leukemia, Myeloid, Acute
PubMed: 35108310
DOI: 10.1371/journal.pone.0263240 -
Haematologica Dec 2022
Meta-Analysis
Topics: Humans; Bridged Bicyclo Compounds, Heterocyclic; Sulfonamides; Leukemia, Myeloid, Acute; Combined Modality Therapy
PubMed: 36453519
DOI: 10.3324/haematol.2022.281453 -
Annals of Palliative Medicine Jul 2021A meta-analysis was performed to examine the clinical efficacy of drugs in the treatment of acute myelogenous leukemia (AML). (Meta-Analysis)
Meta-Analysis
BACKGROUND
A meta-analysis was performed to examine the clinical efficacy of drugs in the treatment of acute myelogenous leukemia (AML).
METHODS
combinations of terms of "acute myeloid leukemia", "fludara", "cytarabine", "cladribine", "aclacinomycin", "granulocyte colony-stimulating factor (G-CSF)", and "hyaluronic acid" were searched in Chinese databases. "acute myelogenous leukemia", "fludara", "cytarabine", "cladribine", "aclacinomycin", "granulocyte colony-stimulating factor", and "hyaluronic acid" were searched in English databases. Review Manager 5.3 was employed for the meta-analysis.
RESULTS
Ultimately, 12 articles were included. Most of the articles had a low-risk bias, and were of medium or high quality. The complete remission rates were tested for heterogeneity [chi-square test (Chi2) =4.10, degrees of freedom (df)=10, I2=0%; P=0.94]. The fixed effect model analysis showed that the difference between experimental participants and controls was considerable [Z=13.15, odds ratio (OR) =12.82, 95% confidence interval (CI): (8.77, 18.76); P<0.01]. The overall effective rates were tested for heterogeneity (Chi2=1.58, df=7, I2=0%; P=0.98), and difference between experimental participants and controls was considerable [Z=10.70, OR =1.32, 95% CI: (7.32,17.89); P<0.01]. The overall adverse reaction rates were tested for heterogeneity (Chi2=0.42, df=5, I2=0%; P=0.99), and the difference between experimental participants and controls was considerable [Z=5.00, OR =0.38, 95% CI: (0.26, 0.55); P<0.01]. The circles of some studies in the funnel diagrams were symmetrical with the midline, the accuracy of included trials was high, the publications were not biased, and the final conclusions were reliable.
CONCLUSIONS
This meta-analysis showed that drug treatments of AML can improve complete remission and total effective rates and reduce adverse reaction rates, and thus are worthy of clinical promotion.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Granulocyte Colony-Stimulating Factor; Humans; Leukemia, Myeloid, Acute; Treatment Outcome
PubMed: 34353076
DOI: 10.21037/apm-21-1390