Occupational benzene exposure and the risk of chronic myeloid leukemia: A meta-analysis of cohort studies incorporating study quality dimensions

2012 ◽  
Vol 55 (9) ◽  
pp. 779-785 ◽  
Author(s):  
Jelle Vlaanderen ◽  
Qing Lan ◽  
Hans Kromhout ◽  
Nathaniel Rothman ◽  
Roel Vermeulen
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Cohort Studies ◽  
Myeloid Leukemia ◽  
Meta Analysis ◽  
Study Quality ◽  
Benzene Exposure ◽  
Quality Dimensions

scholarly journals Occupational Benzene Exposure and the Risk of Lymphoma Subtypes: A Meta-analysis of Cohort Studies Incorporating Three Study Quality Dimensions

2011 ◽  
Vol 119 (2) ◽  
pp. 159-167 ◽  
Author(s):  
Jelle Vlaanderen ◽  
Qing Lan ◽  
Hans Kromhout ◽  
Nathaniel Rothman ◽  
Roel Vermeulen
Keyword(s):  
Cohort Studies ◽  
Meta Analysis ◽  
Study Quality ◽  
Benzene Exposure ◽  
Quality Dimensions

scholarly journals Meta-Analysis of Gastrointestinal Adverse Events from Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1643
Author(s):  
Prahathishree Mohanavelu ◽  
Mira Mutnick ◽  
Nidhi Mehra ◽  
Brandon White ◽  
Sparsh Kudrimoti ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Adverse Events ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Chronic Phase ◽  
Molecular Response ◽  
Gastrointestinal Adverse Events

Tyrosine kinase inhibitors (TKIs) are the frontline therapy for BCR-ABL (Ph+) chronic myeloid leukemia (CML). A systematic meta-analysis of 43 peer-reviewed studies with 10,769 CML patients compared the incidence of gastrointestinal adverse events (GI AEs) in a large heterogeneous CML population as a function of TKI type. Incidence and severity of nausea, vomiting, and diarrhea were assessed for imatinib, dasatinib, bosutinib, and nilotinib. Examination of combined TKI average GI AE incidence found diarrhea most prevalent (22.5%), followed by nausea (20.6%), and vomiting (12.9%). Other TKI GI AEs included constipation (9.2%), abdominal pain (7.6%), gastrointestinal hemorrhage (3.5%), and pancreatitis (2.2%). Mean GI AE incidence was significantly different between TKIs (p < 0.001): bosutinib (52.9%), imatinib (24.2%), dasatinib (20.4%), and nilotinib (9.1%). Diarrhea was the most prevalent GI AE with bosutinib (79.2%) and dasatinib (28.1%), whereas nausea was most prevalent with imatinib (33.0%) and nilotinib (13.2%). Incidence of grade 3 or 4 severe GI AEs was ≤3% except severe diarrhea with bosutinib (9.5%). Unsupervised clustering revealed treatment efficacy measured by the complete cytogenetic response, major molecular response, and overall survival is driven most by disease severity, not TKI type. For patients with chronic phase CML without resistance, optimal TKI selection should consider TKI AE profile, comorbidities, and lifestyle.

scholarly journals Adherence to Tyrosine Kinase Inhibitor Therapy in Patients with Chronic Myeloid Leukemia: Meta-Analyses of Prevalence Rates By Measurement Method

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3610-3610 ◽  
Author(s):  
Ziyad Alrabiah ◽  
Abdulaziz Alhossan ◽  
Seongseok Yun ◽  
Karen MacDonald ◽  
Ivo Abraham
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Meta Analysis ◽  
Medication Possession Ratio ◽  
Structured Interview ◽  
Proportion Of Days Covered ◽  
Equity Ownership ◽  
Meta Analyses

Abstract Introduction: First- (imatinib) and second-generation (dasatinib, nilotinib) tyrosine kinase inhibitors are the standard of care in the management of chronic myeloid leukemia. Despite their high efficacy and the convenience of oral administration, studies have reported variation in patient medication behavior with non-adherence rates varying from low to moderate based on definition and measurement method. We conducted study-level meta-analyses stratified by measurement method to quantify adherence prevalence rates in chronic myeloid leukemia patients as reported in non-controlled "real-life" studies. Methods: We searched PubMed, Embase, and Cochrane Library for non-controlled studies reporting adherence or non-adherence rates to tyrosine kinase inhibitor treatment in chronic myeloid leukemia patients across various methods of measurement. For retained studies, adherence rates and 95% confidence interval (95% CI) were extracted or calculated; and grouped by method of measurement. Random-effects meta-analyses were performed to account for estimated (Q, I2, tau2) within and between study heterogeneity, and associated forest plots were generated. Analyses were done using Comprehensive Meta-Analysis V.3. Results: From 649 publications yielded by the search, 40 articles and abstracts were retained. Measurement methods included structured interview, medical/pharmacy chart review, medication possession ratio, proportion of days covered, electronic monitoring, and self-report. Electronic monitoring and self-report were used in one study each and thus excluded from meta-analysis. Table 1 summarizes, by the remaining four methods, the number of studies and patients included in each meta-analysis, the estimated adherence event rates with 95%CI, and heterogeneity indices. In random-effects analyses, adherence rate estimates as measured by each method ranged (in descending order) from 0.75 (95%CI=0.66-0.82) for structured interview, 0.68 (95%CI=0.54-0.79) for medical/pharmacy chart review, 0.57 (95%CI=0.47-0.67) for medication possession ratio, to 0.56 (95%CI=0.36-0.74) for proportion of days covered. All four analyses showed significant heterogeneity. Conclusion: Our meta-analyses using clinical data (structured interview; medical/pharmacy chart review) indicate that, while the majority of chronic myeloid leukemia patients are adherent to their tyrosine kinase inhibitor regimens, between 1/3rd and 1/4th of them are not. Indirect methods using prescription claims data (medication possession ratio; proportion of days covered) yielded lower adherence rates, though caution about such indirect results is warranted. Considering evidence linking adherence to impaired cytogenetic (Noens et al, Blood 2009) and molecular response (Marin et al, J Clin Oncol 2010), clinicians should integrate adherence assessment and enhancement into routine clinical practice. Table 1 Table 1. Disclosures MacDonald: Matrix45: Employment, Equity Ownership; Ex Ante International: Equity Ownership. Abraham:Matrix45: Equity Ownership; Belgamis: Equity Ownership; Ex Ante International: Equity Ownership.

Impact of SLC22A1 and CYP3A5 genotypes on imatinib response in chronic myeloid leukemia: A systematic review and meta-analysis

2018 ◽  
Vol 131 ◽  
pp. 244-254 ◽  
Author(s):  
Sarah Cargnin ◽  
Gloria Ravegnini ◽  
Simona Soverini ◽  
Sabrina Angelini ◽  
Salvatore Terrazzino
Keyword(s):  
Systematic Review ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Meta Analysis

scholarly journals Arterial Hypertension and Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Olga Mulas ◽  
Giovanni Caocci ◽  
Brunella Mola ◽  
Giorgio La Nasa
Keyword(s):  
Systematic Review ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Cardiovascular Complication ◽  
Third Generation ◽  
Pubmed Database

Background: 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.Methods: 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.Results: 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, I2=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).Conclusion: Hypertension is a common cardiovascular complication in CML patients treated with second- or third-generation TKI.

scholarly journals The Role of the Newer Tyrosine Kinase Inhibitors As First Line Treatment in Chronic Phase Chronic Myeloid Leukemia – an Updated Meta-Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4563-4563
Author(s):  
Ronit Gurion ◽  
Liat Vidal ◽  
Avi Leader ◽  
Pia Raanani ◽  
Anat Gafter-Gvili
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Meta Analysis ◽  
Chronic Phase ◽  
Molecular Response ◽  
Line Treatment ◽  
First Line ◽  
Time Points ◽  
Grade 3 ◽  
First Line Treatment

Abstract Background: Imatinib, nilotinib and dasatinib are all considered first line treatment in chronic phase (CP) chronic myeloid leukemia (CML) patients. The choice of the most suitable tyrosine kinase inhibitor (TKI) for an individual patient is influenced by multiple factors including disease characteristics, patient comorbidities and preferences, as well as each TKI's unique profile of adverse events. A meta-analysis of second generation TKIs as first line treatment for patients with CML was published by our group in 2011. In view of the recently published long term results of three of the trials included in the previous meta-analysis and data from two new trials, we decided to update our data. Objectives: To evaluate the efficacy and toxicity of different TKIs as first line treatment for patients with CML. Methods: Systematic review and meta-analysis of randomized controlled trials comparing first line treatment with the newer TKIs (nilotinib, dasatinib, bosutinib and ponatinib) to imatinib in patients with CP-CML. The MEDLINE, conference proceedings and references were searched until August 2014. Two reviewers appraised the quality of trials and extracted data. The following outcomes were assessed: complete cytogenetic response (CCyR); major molecular response (MMR); complete molecular response (CMR), defined as a 4.5 log reduction in BCR-ABL transcripts; early molecular response, defined as BCR-ABL transcript levels of 10% or less at 3 months; progression to accelerated phase (AP) / blastic crisis (BC); all-cause mortality (ACM) and toxicity. Relative risks (RR) were estimated and pooled. Random-effect model was used in all analysis. Results: Our search yielded six trials including 2,426 patients. These trials compared the effects of nilotinib, dasatinib, bosutinib or ponatinib to imatinib. Data from the six trials were available for analysis of MMR. Treatment with the newer TKIs significantly improved MMR at all-time points (3, 12, 18, 24 and 48 months) compared to imatinib (Table 1). Of note, the newer TKIs significantly increased the rate of CMR compared to imatinib at 12 months (RR 2.68, 95% CI 1.64-4.36, 5 trials, figure 1) and at 24 months (RR 2.04, 95% CI 1.62-2.57, 3 trials). Moreover, there was a statistically significant advantage in favor of the newer TKIs as compared to imatinib in terms of early molecular response at 3 months (RR 1.34, 95% CI 1.27-1.41, 5 trials). Importantly, progression rate to AP/BC at 24 months was significantly lower with the newer TKIs in comparison with imatinib (RR 0.35, 95% CI 0.20-0.61, 4 trials). However there was no difference in ACM (RR 0.73, 95% CI 0.46-1.15, 4 trials). We conducted a meta-analysis for specific adverse events according to the distinct toxicity profile of the different TKIs. Severe peripheral arterial occlusive disease occurs more frequently in the newer TKIs arm (i.e. nilotinib and ponatinib) (RR 8.13, 95% CI 1.51-43.83, 2 trials) than in the imatinib arm. In addition, pleural effusion requiring discontinuation occurs at a higher rate in the newer TKIs arm (RR 4.61, 95% CI 1.31-16.23, 4 trials; dasatinib and bosutinib vs. imatinib). Regarding hematologic toxicity including grade 3-4 anemia and neutropenia, there was no difference between the two arms (all newer TKIs vs. imatinib). However, regarding thrombocytopenia grade 3-4, there were more events with thrombocytopenia in the newer TKIs arm compared to imatinib (RR 1.41, 95% CI 1.01-1.97). Conclusions: With a longer follow-up of 4 years, the newer TKIs remain more potent than imatinib in terms of MMR, CMR and early molecular response. Yet, an effect on overall survival cannot be shown. Since CMR is a prerequisite for treatment discontinuation, the newer TKIs can potentially facilitate cessation of treatment more frequently than imatinib. These data should be taken into consideration in choosing treatment for a newly diagnosed CML patient. Table 1 – MMR at different time points Time point Relative risk 95% Confidence of interval No. of trials 3 months 6.63 2.31-19.01 5 12 months 1.68 1.48-1.89 6 18 months 1.37 1.18-1.59 4 24 months 1.28 1.06-1.54 4 48 months 1.20 1.05-1.38 3 Figure 1 – CMR at 12 months Figure 1 –. CMR at 12 months Disclosures No relevant conflicts of interest to declare.

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