Association of Interleukin 10 (IL-10) Gene Polymorphism (819T > C) with Susceptibility to Acute Myeloid Leukemia: A Meta-Analysis

Background: Studies reported an association between interleukin (IL)-10 -819T>C polymorphism and the risk of developing Acute myeloid leukemia (AML), however due to inconsistency among these results, relationship between IL-10 -819T>C polymorphism and AML remained unclear. We herein performed this meta-analysis to investigate the association of IL-10 -819T >C polymorphism with the risk of AML. Methods: A systematic search through PubMed, Embase, Scopus, Cochrane Library and OpenGrey was performed from inception to Jan 2021. Odds ratios (OR) with their corresponding 95% confidence intervals (CI) for five possible genetic models were calculated. Heterogeneity was assessed using the Cochran Q test and the I2 statistic. A total of 404 AML cases and 635 healthy controls were included in our meta-analysis. Results: Our results indicated no statically significant association between IL-10 -819T>C polymorphism and the risk of developing AML; dominant model (OR=0.87, 95% CI=0.42–1.81); recessive model (OR=1.17, 95% CI = 0.43–3.16); allelic model (OR=1.00, 95% CI=0.54–1.88); CC vs. TT (OR=1.00,95% CI=0.30–3.36); and TC vs. TT (OR=0.80, 95%CI =0.46–1.37). Conclusion: IL-10 -819T > C polymorphism is not associated with the risk of AML. However further studies focusing on other parameters such as sex, gene-gene interactions and environmental factors are required to reveal the true association of IL-10 -819T > C polymorphism with AML.

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FLT3 Inhibitors as Maintenance Therapy Post Hematopoietic Cell Transplantation for Acute Myeloid Leukemia (AML): A Systematic Review and Meta-Analysis

10.21203/rs.3.rs-1127079/v1 ◽

2021 ◽

Author(s):

Xinhui Zheng ◽

Xiangjun Li ◽

Er-Lie Jiang ◽

Liwei Lv

Keyword(s):

Acute Myeloid Leukemia ◽

Cell Transplantation ◽

Myeloid Leukemia ◽

Hematopoietic Cell Transplantation ◽

Meta Analysis ◽

Cochrane Library ◽

Hematopoietic Stem ◽

Flt3 Inhibitors ◽

Before And After ◽

Acute Myeloid

Abstract The purpose of this paper is to systematically analyze the outcome of FLT3 inhibitors maintenance treatment following hematopoietic stem cell transplantation (HSCT) for patients suffering from FLT3-ITD-mutated acute myeloid leukemia (AML). Pubmed, Embase, and Cochrane Library databases were retrieved before November 2021. Fifteen studies were included eventually containing six without control and nine with control. Thirteen studies evaluated sorafenib, and two assessed quizartinib and midostaurin, separately. Via survival analysis, the main outcomes in the FLT3 inhibitors group were improved greatly with the hazard ratio(HR) of overall survival of 0.38 (95% confidence interval [CI], 0.29-0.49; P < 0.001), HR of leukemia-free survival of 0.35 (95%CI, 0.27-0.47; P < 0.001) and HR of cumulative incidence of relapse of 0.32 (95%CI, 0.23-0.45; P < 0.001). Moreover, the TKI use didn’t seem to increase the incidence of graft-versus-host disease (GVHD) and adverse effects in statistics. Through subgroup analysis, MRD-positive patients before and after HCT, and MRD-negative patients before HCT might benefit a lot from sorafenib maintenance.

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Clinical Benefits and Safety of FMS-Like Tyrosine Kinase 3 Inhibitors in Various Treatment Stages of Acute Myeloid Leukemia: A Systematic Review, Meta-Analysis, and Network Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.686013 ◽

2021 ◽

Vol 11 ◽

Author(s):

Qingyu Xu ◽

Shujiao He ◽

Li Yu

Keyword(s):

Systematic Review ◽

Acute Myeloid Leukemia ◽

Tyrosine Kinase ◽

Myeloid Leukemia ◽

Meta Analysis ◽

Cochrane Library ◽

Therapeutic Effects ◽

Free Survival ◽

Increased Risk ◽

Acute Myeloid

BackgroundGiven the controversial roles of FMS-like tyrosine kinase 3 inhibitors (FLT3i) in various treatment stages of acute myeloid leukemia (AML), this study was designed to assess this problem and further explored which FLT3i worked more effectively.MethodsA systematic review, meta-analysis and network meta-analysis (NMA) were conducted by filtering PubMed, Embase, Cochrane library, and Chinese databases. We included studies comparing therapeutic effects between FLT3i and non-FLT3i group in AML, particularly FLT3(+) patients, or demonstrating the efficiency of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in FLT3(+) AML. Relative risk (RR) with 95% confidence intervals (CI) was used for estimating complete remission (CR), early death and toxicity. Hazard ratio (HR) was used to assess overall survival (OS), event-free survival (EFS), relapse-free survival (RFS) and cumulative incidence of relapse (CIR).ResultsAfter addressing all criteria, 39 studies were eventually analyzed. Better CR was accomplished by FLT3i in untreated AML (RR 0.88, p = 0.04) and refractory and relapsed FLT3(+) AML (rrAML) (RR 0.61, p < 0.01) compared to non-FLT3i arm, followed by improved survival (untreated AML: OS, HR 0.76; EFS, HR 0.67; RFS, HR 0.72; all p < 0.01; FLT3(+) rrAML: OS, HR 0.60, p < 0.01; RFS, HR 0.40, p = 0.01). In addition, allo-HSCT improved survival in FLT3(+) AML (OS, HR 0.53; EFS, HR 0.50; RFS, HR 0.57; CIR, HR 0.26; all p < 0.01), which was further prolonged by FLT3i administrated after allo-HSCT (OS, HR 0.45; RFS, HR 0.34; CIR, HR 0.32; all p < 0.01). Additionally, FLT3i consistently improved OS (p < 0.05) regardless of FLT3-ITD ratio, when compared to non-FLT3i group. Besides, FLT3i showed significantly increased risk of thrombocytopenia, neutropenia, anemia, skin- and cardiac-related adverse effects, increased alanine aminotransferase, and increased risk of cough and dyspnea (p < 0.05). In NMA, gilteritinib showed the highest probability for improved prognosis.ConclusionsFLT3i safely improved prognosis in induction/reinduction stage of FLT3(+) AML and further boosted survival benefits from allo-HSCT as maintenance therapy, suggesting better prognosis if FLT3i is combined before and after allo-HSCT. In NMA, gilteritinib potentially achieved the best prognosis, which should be identified in direct trials.

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Comparison Between Decitabine and Azacitidine for Patients With Acute Myeloid Leukemia and Higher-Risk Myelodysplastic Syndrome: A Systematic Review and Network Meta-Analysis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.701690 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jiale Ma ◽

Zheng Ge

Keyword(s):

Systematic Review ◽

Acute Myeloid Leukemia ◽

Complete Remission ◽

Myelodysplastic Syndrome ◽

Myeloid Leukemia ◽

Meta Analysis ◽

Statistical Significance ◽

Cochrane Library ◽

Grade 3 ◽

Acute Myeloid

Background: The hypomethylating agents (HMAs) azacitidine (AZA) and decitabine (DAC) have been widely used in patients with acute myeloid leukemia (AML) and higher-risk myelodysplastic syndrome (HR-MDS). However, few direct clinical trials have been carried out to compare the efficacy and adverse events (AEs) between these two agents. The clinical choice between them is controversial. A systematic review and network meta-analysis (NMA) was performed to compare the efficacy, safety, and survival of DAC and AZA in AML and HR-MDS patients.Methods: We systematically searched MEDLINE, Embase, Web of Science, and Cochrane Library through March 15, 2021. Randomized controlled trials (RCTs) on AML or HR-MDS patients comparing the efficacy and safety between DAC and AZA or comparing one of HMAs to conventional care regimens (CCR) were selected.Results: Eight RCTs (n = 2,184) were identified in the NMA. Four trials compared AZA to CCR, and four compared DAC to CCR. Direct comparisons indicated that, compared to CCR, both AZA and DAC were associated with higher overall response (OR) rate (AZA vs. CCR: relative risk (RR) = 1.48, 95% CI 1.05–2.1; DAC vs. CCR: RR = 2.14, 95% CI 1.21–3.79) and longer overall survival (OS) (AZA vs. CCR: HR = 0.64, 95% CI 0.50–0.82; DAC vs. CCR: HR = 0.84, 95% CI 0.72–0.98), and AZA showed higher rate of complete remission with incomplete blood count recovery (CRi) (HR = 2.52, 95% CI 1.27–5). For the indirect method, DAC showed a higher complete remission (CR) rate than AZA in patients with both AML (RR = 2.28, 95% CI 1.12–4.65) and MDS (RR = 7.57, 95% CI 1.26–45.54). Additionally, DAC significantly increased the risk of 3/4 grade anemia (RR = 1.61, 95% CI: 1.03–2.51), febrile neutropenia (RR = 4.03, 95% CI: 1.41–11.52), and leukopenia (RR = 3.43, 95% CI 1.64–7.16) compared with AZA. No statistical significance was found for the other studied outcomes.Conclusion: Compared to CCR, both AZA and DAC can promote outcomes in patients with AML and HR-MDS. DAC showed higher efficacy especially CR rate than AZA (low-certainty evidence), while AZA experienced lower frequent grade 3/4 cytopenia than patients receiving DAC treatment.

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