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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 -
Advances in Therapy Dec 2023Clofarabine monotherapy at a dose of 52 mg/m per day was approved in the USA in 2004 for the treatment of relapsed or refractory acute lymphoblastic leukemia (R/R ALL)... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Clofarabine monotherapy at a dose of 52 mg/m per day was approved in the USA in 2004 for the treatment of relapsed or refractory acute lymphoblastic leukemia (R/R ALL) in patients aged 1-21 years after at least two prior regimens. To address a post-marketing requirement for additional evidence of the clinical benefit of clofarabine in its approved indication, a meta-analysis of patient-level data was conducted.
METHODS
A systematic literature review was conducted, using the Dr.Evidence software platform, DOC Search, and Embase, to identify clinical trials with patients with R/R ALL who received clofarabine monotherapy at 52 mg/m. The primary endpoint was complete remission (CR). Secondary endpoints were overall remission (OR, defined by CR or CR with either incomplete platelet recovery or incomplete neutrophil and platelet recovery), duration of response, overall survival (OS), and safety.
RESULTS
A total of 754 patients in 12 clinical studies were analyzed including 682 patients with R/R ALL treated with clofarabine monotherapy at 52 mg/m; of them, 374 were aged < 22 years (pediatric population). Rates of CR and OR were 16% (95% confidence interval [CI] 7, 26) and 28% (95% CI 20, 37), respectively, in the pediatric population and 12% (95% CI 5, 21) and 21% (95% CI 13, 31) in the overall population. Median OS (evaluable in three studies in pediatric patients) was 3.7 months (95% CI 0.1, 31.4), reaching 10.1 months (95% CI 0.3, 68.9) for those achieving OR. Sensitivity analyses supported these findings. The most frequent grade 3-4 adverse events were liver abnormalities, anemia, diarrhea, and febrile neutropenia.
CONCLUSION
In this meta-analysis, CR duration and median OS in pediatric patients with R/R ALL appeared to be slightly longer than in the phase II study. No new safety signals were identified. Results support the use of clofarabine monotherapy in its approved indication.
Topics: Child; Humans; Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Clofarabine; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Clinical Trials as Topic
PubMed: 37819554
DOI: 10.1007/s12325-023-02696-7 -
Prostate Cancer and Prostatic Diseases Mar 2023Immunotherapy has not achieved improvement of survival in prostate cancer patients. Myeloid-derived suppressor cells (MDSCs) in tumor microenvironment can hamper its... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Immunotherapy has not achieved improvement of survival in prostate cancer patients. Myeloid-derived suppressor cells (MDSCs) in tumor microenvironment can hamper its efficacy. Some preclinical studies explored the role of MDSCs in prostate cancer development. We aimed to verify the availability of studies exploring the prognostic effect of circulating MDSCs in prostate cancer patients.
METHODS
We systematically selected studies for a meta-analysis, which compares survival between prostate cancer patients with high vs low circulating MDSC levels. We extracted or calculated hazard ratios (HRs) and relative 95% confidence intervals (CIs) in terms of overall survival (OS) from selected studies. We calculated the pooled HR and relative 95% CIs and estimated publication bias.
RESULTS
Among 133 studies retrieved from search on Pubmed, 5 eligible studies (236 prostate cancer patients) met inclusion criteria. High circulating MDSC levels are associated with a worse OS (HR = 2.19; 95%CI = 1.51-3.17). Heterogeneity was not significant (I = 0%; p = 0.64). Publication bias was also not significant (Egger's test, p = 0.09).
CONCLUSIONS
High levels of circulating MDSCs induce a worse OS in prostate cancer patients than in those with low levels. This finding supports the importance of MDSC detection and targeting also in prostate cancer patients.
Topics: Male; Humans; Prostatic Neoplasms; Myeloid-Derived Suppressor Cells; Prognosis; Immunotherapy; Tumor Microenvironment
PubMed: 36411316
DOI: 10.1038/s41391-022-00615-5 -
Annales de Dermatologie Et de... Dec 2016Answering the question « what's new in internal medecine in 2016? » is very challenging. We used 3 methods of article selection to reduce the selection bias: 3... (Review)
Review
Answering the question « what's new in internal medecine in 2016? » is very challenging. We used 3 methods of article selection to reduce the selection bias: 3 authors, a systematic review of the articles discussed in the weekly bibliographic meeting of our unit (Dermatology department, Saint-Louis Hospital, Paris, France) and a selection of the best articles by several internal medecine practitioners in Paris. Eleven « hot topics » were analyzed: i/lowering cholesterol level but not blood blessure has a significant impact on cardiovascular morbi-mortality in cardiovascular intermediate risk patients; ii/the « treat to treat target » is efficient in psoriatic arthritis; iii/ a genotype/ phenotype correlation favors the separation of ileal Crohn's disease, colonic Crohn's disease and ulcerative colitis; iv/ tocilizumab treatment (anti-IL-6 monoclonal antibody ) is very efficient in giant cell arteritis and slightly efficient in systemic sclerosis; v/ combination therapy using methotrexate plus steroids compared with steroids alone becomes the « gold standard » treatment for juvenile dermatomyositis; vi/ dupilumab treatment (antibody blocking IL-4 and IL-13 receptors) is not only efficient in atopic dermatitis but also in asthma; vii/ think of eosinophilic oesophagitis in a patient with atopic dermatitis and dypshagia or food impaction; viii/ genetic A2 protein dysfunction induces NF-kB hyperactivation and an autoinflammatory disorder with features similar to Behcet's disease; ix/ no new biotherapies have shown high efficacy in systemic lupus erythematosus; x/ nanoparticles loaded with autoantigens induce Tregs and Bregs and may be a promising therapeutic option to treat auto-immune disease in the future; xi/ ipilimumab treatment (anti-CTLA4 antibody, immune checkpoint inhibitor) may induce complete remission in acute myeloid leukemia patients relapsing after haematological stem cell transplantation. Year 2016 is full of great discoveries in internal medicine keeping the dermatologist brain fully open minded.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antihypertensive Agents; Antineoplastic Agents, Immunological; Arthritis, Rheumatoid; Asthma; Autoimmune Diseases; Behcet Syndrome; Cardiovascular Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammatory Bowel Diseases; Internal Medicine; Ipilimumab; Skin Diseases
PubMed: 29429506
DOI: 10.1016/S0151-9638(18)30046-2 -
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 -
Annals of Hematology Aug 2014Diagnosis and classification of acute myeloid leukemia (AML) are based on morphology and genetics. An increasing number of gene mutations have been found, and some are... (Meta-Analysis)
Meta-Analysis Review
Prognostic significance of FLT3 internal tandem duplication, nucleophosmin 1, and CEBPA gene mutations for acute myeloid leukemia patients with normal karyotype and younger than 60 years: a systematic review and meta-analysis.
Diagnosis and classification of acute myeloid leukemia (AML) are based on morphology and genetics. An increasing number of gene mutations have been found, and some are used for risk classification in AML patients with normal karyotype (cytogenetically normal (CN)-AML). In this systematic review and meta-analysis, we examined three frequent mutations in CN-AML: mutations of fms-related tyrosine kinase 3 (FLT3-ITD), mutated nucleophosmin (NPM1), and mutations of the CCAAT enhancer-binding protein alpha (CEBPA) gene. A systematic literature search of publications listed in the electronic databases (Embase, Pubmed, Healthstar, BIOSIS, ISI Web of Knowledge and Cochrane) from 2000 up to March 2012 was performed (Fig. 1). Nineteen studies were included and qualitatively analyzed. Two to four studies entered the quantitative meta-analysis incorporating 1,378 to 1,942 patients with CN-AML. Meta-analysis for overall survival (OS) and relapse-free survival (RFS) showed FLT3-ITD to predict an unfavorable prognosis, with hazard ratios (HR) of 1.86 and 1.75, respectively. In contrast, meta-analysis of the impact of NPM1 and CEBPA mutations on OS yielded an HR of 0.56 for each mutation, while analysis of impact on RFS produced HRs of 0.37 and 0.42, respectively. This systematic review and meta-analysis aimed to evaluate the prognostic value of mutations in the NPM1, CEBPA, and FLT3 genes. FLT3-ITD was associated with worse prognosis, whereas mutations in NPM1 and CEBPA genes were associated with a favorable prognosis.
Topics: Adult; Age Factors; CCAAT-Enhancer-Binding Proteins; Clinical Trials as Topic; Disease-Free Survival; Female; Humans; Karyotype; Leukemia, Myeloid, Acute; Male; Middle Aged; Mutation; Nuclear Proteins; Nucleophosmin; Proportional Hazards Models; Survival Analysis; Tandem Repeat Sequences; Treatment Outcome; Young Adult; fms-Like Tyrosine Kinase 3
PubMed: 24801015
DOI: 10.1007/s00277-014-2072-6 -
Disease Markers 2018Angiogenin (ANG) is a multifunctional angiogenic protein that participates in both normal development and diseases. Abnormal serum ANG levels are commonly reported in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Angiogenin (ANG) is a multifunctional angiogenic protein that participates in both normal development and diseases. Abnormal serum ANG levels are commonly reported in various diseases. However, whether ANG can serve as a diagnostic or prognostic marker for different diseases remains a matter of debate.
METHODS
Here, we performed a systematic review and meta-analysis of the literature utilizing PubMed, Web of Science, and Scopus search engines to identify all publications comparing plasma or serum ANG levels between patients with different diseases and healthy controls, as were studies evaluating circulating ANG levels in healthy populations, pregnant women, or other demographic populations.
RESULTS
This study demonstrated that the serum ANG concentration in healthy populations was 336.14 ± 142.83 ng/ml and remained relatively stable in different populations and regions. We noted no significant differences in serum ANG levels between patients and healthy controls, except in cases in which patients suffered from cancer or cardiovascular diseases. The serum ANG concentrations were significantly higher in patients who developed colorectal cancer, acute myeloid leukemia, multiple myeloma, myelodysplastic syndromes, and heart failure than those in healthy controls.
CONCLUSION
ANG has the potential of being a serum biomarker for cancers and cardiovascular diseases.
Topics: Angiotensins; Biomarkers; Case-Control Studies; Colorectal Neoplasms; Female; Heart Failure; Humans; Leukemia, Myeloid; Male; Multiple Myeloma; Myelodysplastic Syndromes
PubMed: 29736193
DOI: 10.1155/2018/1984718 -
European Journal of Pediatrics Jan 2023Phototherapy is the main treatment of neonatal hyperbilirubinemia to prevent encephalopathy. It is generally believed to be safe; however, some studies have shown it... (Meta-Analysis)
Meta-Analysis
Phototherapy is the main treatment of neonatal hyperbilirubinemia to prevent encephalopathy. It is generally believed to be safe; however, some studies have shown it might be associated with cancer development. In this systematic review and meta-analysis, we aimed to assess the effect of neonatal phototherapy on future cancer risk. A systematic search in 13 databases was conducted in December 2018 and updated in August 2022 to identify studies that report cancer development after exposure to phototherapy. Throughout the study period, regular manual searches were also conducted to include new studies. A meta-analysis using R programming language was done in which the odds ratios (ORs) with 95% confidence intervals (CIs) were estimated and pooled using the reported adjusted and unadjusted data. Fifteen studies were included. A statistically significant association was detected between neonatal phototherapy and any type of cancer (OR 1.24; 95% CI 1.1, 1.4), any hematopoietic cancer (OR 1.49; 95% CI 1.17, 1.91), any leukemia (OR 1.35; 95% CI 1.08, 1.67), and myeloid leukemia (OR 2.86; 95% CI 1.4, 5.84). The other investigated cancers (lymphoid leukemia, Hodgkin's lymphoma, kidney cancer, nervous system cancer, and skin cancer) were not associated with phototherapy. Conclusions: Phototherapy may carry a possible risk of future cancers. Future research is needed to quantify the magnitude of the cancer risk. These future studies should consider predictors of preterm birth or exclude premature babies from their analysis. What is Known • There were various reports about the possible association between phototherapy in neonates and the increased risk of cancer in the future. What is New • A statistically significant association between phototherapy and various hematopoietic cancers (especially myeloid leukemia) was recorded. • The effect of the duration of phototherapy on the increased risk of hematopoietic cancers is yet unclear.
Topics: Female; Infant, Newborn; Humans; Premature Birth; Infant, Premature; Hyperbilirubinemia, Neonatal; Phototherapy; Skin Neoplasms; Jaundice, Neonatal
PubMed: 36352244
DOI: 10.1007/s00431-022-04675-6 -
Cancer Treatment Reviews Feb 2021This review and meta-analysis examined published evidence of peptide receptor radionuclide therapy (PRRT) re-treatment efficacy and safety in patients with advanced... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This review and meta-analysis examined published evidence of peptide receptor radionuclide therapy (PRRT) re-treatment efficacy and safety in patients with advanced neuroendocrine tumors (NETs).
METHODS
Embase, MEDLINE, MEDLINE In-Progress, and Cochrane CENTRAL were searched (database inception-present) to identify evidence of efficacy and safety of PRRT re-treatment in adults with NETs previously treated with Lu- and/or Y-PRRT. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) from time of re-treatment were assessed. Data were pooled using medians and variance for time-to-event outcomes and inverse-variance weighted proportions (Freeman-Tukey method) for binary outcomes.
RESULTS
Of 567 studies screened, 13 reported re-treatment efficacy outcomes. In random-effects meta-analyses of Lu-PRRT re-treatment, median PFS (N = 7 studies [414patients]) was 12.52 months (95% CI 9.82-15.22) with moderate heterogeneity across studies (I = 50.5%), median OS (N = 2 [194 patients]) was 26.78 months (95% CI 18.73-34.83) with moderate-to-high heterogeneity (I = 57.5%), and DCR (N = 8 [347 patients]) was 71% (95% CI 66-75) with high heterogeneity (I = 81.5%). PFS was similar with either Lu-PRRT re-treatment alone or in combination with Y-PRRT. Grade 3/4 adverse events occurred in 5% (95% CI 2-8) of patients receiving Lu-PRRT re-treatment (N = 5 [271 patients]) with few grade 3/4 renal toxicities (0% [95% CI 0-1]). Pooled myelodysplastic syndrome and acute myeloid leukemia incidence was 0% (95%CI 0-2).
CONCLUSION
Re-treatment with Lu-PRRT provided encouraging median PFS in patients with NETs with a safety profile similar to initial PRRT.
Topics: Clinical Trials, Phase III as Topic; Humans; Neuroendocrine Tumors; Progression-Free Survival; Radiopharmaceuticals; Radiotherapy; Randomized Controlled Trials as Topic; Receptors, Peptide; Treatment Outcome
PubMed: 33418096
DOI: 10.1016/j.ctrv.2020.102141 -
Annals of Hematology Aug 2014Glutathione S-transferases (GSTs) contribute to the metabolism of different xenobiotics and anticancer drugs and confer protection against oxidative stress thus may... (Meta-Analysis)
Meta-Analysis Review
Glutathione S-transferases (GSTs) contribute to the metabolism of different xenobiotics and anticancer drugs and confer protection against oxidative stress thus may influence the treatment outcome of acute myeloid leukemia (AML). Studies regarding the association between GSTT1 and GSTM1 polymorphisms and treatment outcome in AML patients showed an inconsistent result. A systematic review and meta-analysis were performed to further explore this association. PubMed, Hartford User Group Exchange (HUGE), and China National Knowledge Infrastructure (CNKI) databases were searched for all related publications. Statistical analyses were analyzed by using RevMan 5.0 and Stata 9.0 softwares. A total of 1,837 patients in 11 studies were included. GSTT1 null genotype was found to be significantly associated with a reduced response after first course of induction chemotherapy (odds ratio (OR) = 0.894, 95 % confidence interval (CI) = 0.818-0.977, P = 0.013), progression-free survival (PFS; hazard ratio (HR) = 0.698, 95 % CI = 0.520-0.937, P = 0.017), and overall survival (OS; HR = 0.756, 95 % CI = 0.618-0.925, P = 0.007) in Asian population. GSTM1/GSTT1 double-null genotype was also identified to be significantly associated with response after the first course of induction chemotherapy (OR = 0.40, 95 % CI = 0.24-0.67, P = 0.0003). Our study suggested that GSTT1 null genotype and GSTT1/GSTM1 double-null genotype were associated with a worse treatment outcome for AML patients, especially in Asian population.
Topics: Adolescent; Adult; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; China; Cytarabine; Disease-Free Survival; Female; Gene Deletion; Genotype; Glutathione Transferase; Humans; Inactivation, Metabolic; Leukemia, Myeloid, Acute; Male; Middle Aged; Mutation; Neoplasm Proteins; Odds Ratio; Pharmacogenetics; Remission Induction; Survival Analysis; Treatment Outcome; Young Adult
PubMed: 24994605
DOI: 10.1007/s00277-014-2050-z