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Annals of Hematology Jun 2024Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between... (Meta-Analysis)
Meta-Analysis
Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between JAK2V617F allele burden (also known as variant allele frequency) and the relevant clinical characteristics. Numerous studies have reported associations between allele burden and both hematologic and clinical features. While there are strong indications linking high allele burden in PV patients with symptoms and clinical characteristics, not all associations are definitive, and disparate and contradictory findings have been reported. Hence, this study aimed to synthesize existing data from the literature to better understand the association between JAK2V617F allele burden and relevant clinical correlates. Out of the 1,851 studies identified, 39 studies provided evidence related to the association between JAK2V617F allele burden and clinical correlates, and 21 studies were included in meta-analyses. Meta-analyses of correlation demonstrated that leucocyte and erythrocyte counts were significantly and positively correlated with JAK2V617F allele burden, whereas platelet count was not. Meta-analyses of standardized mean difference demonstrated that leucocyte and hematocrit were significantly higher in patients with higher JAK2V617F allele burden, whereas platelet count was significantly lower. Meta-analyses of odds ratio demonstrated that patients who had higher JAK2V617F allele burden had a significantly greater odds ratio for developing pruritus, splenomegaly, thrombosis, myelofibrosis, and acute myeloid leukemia. Our study integrates data from approximately 5,462 patients, contributing insights into the association between JAK2V617F allele burden and various hematological parameters, symptomatic manifestations, and complications. However, varied methods of data presentation and statistical analyses prevented the execution of high-quality meta-analyses.
Topics: Polycythemia Vera; Janus Kinase 2; Humans; Alleles; Gene Frequency; Amino Acid Substitution; Mutation, Missense
PubMed: 38652240
DOI: 10.1007/s00277-024-05754-4 -
Archives of Disease in Childhood Oct 2020To determine the safety of ceftriaxone in paediatric patients and systematically evaluate the categories and incidences of adverse drug reactions (ADRs) of ceftriaxone...
OBJECTIVE
To determine the safety of ceftriaxone in paediatric patients and systematically evaluate the categories and incidences of adverse drug reactions (ADRs) of ceftriaxone in paediatric patients.
METHODS
We performed a systematic search in Medline, PubMed, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, International Pharmaceutical Abstracts and bibliographies of relevant articles up to December 2018 for all types of studies that assessed the safety of ceftriaxone in paediatric patients aged ≤18 years.
RESULTS
112 studies met the inclusion criteria involving 5717 paediatric patients who received ceftriaxone and reported 1136 ADRs. The most frequent ADRs reported in prospective studies were gastrointestinal (GI) disorders (37.4 %, 292/780), followed by hepatobiliary disorders (24.6%, 192/780). Serious ADRs leading to withdrawal or discontinuation of ceftriaxone were reported in 86 paediatric patients. Immune haemolytic anaemia (34.9%, 30/86) and biliary pseudolithiasis (26.7%, 23/86) were the two major causes. Haemolytic anaemia following intravenous ceftriaxone led to death in 11 children whose primary disease was sickle cell disease. Almost all biliary pseudolithiasis are reversible. However, the incidence was high affecting one in five paediatric patients (20.7%).
CONCLUSIONS
GI ADRs are the most common toxicity of ceftriaxone in paediatric patients. Immune haemolytic anaemia and biliary pseudolithiasis are the most serious ADRs and the major reasons for discontinuation of ceftriaxone. Immune haemolytic anaemia is more likely in children with sickle cell disease and may cause death. Ceftriaxone should be used with caution in children with sickle cell disease.
TRIAL REGISTRATION NUMBER
CRD42017055428.
Topics: Anemia, Hemolytic; Anemia, Sickle Cell; Anti-Bacterial Agents; Ceftriaxone; Diarrhea; Digestive System Diseases; Exanthema; Humans; Nephrolithiasis; Pediatrics; Thrombocytosis; Ureteral Calculi; Urination Disorders
PubMed: 32144089
DOI: 10.1136/archdischild-2019-317950 -
Acta Haematologica 2020We performed this systematic review and meta-analysis to compare the efficacy of new-generation tyrosine kinase inhibitors (NG-TKIs; including dasatinib, nilotinib,... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUNDS
We performed this systematic review and meta-analysis to compare the efficacy of new-generation tyrosine kinase inhibitors (NG-TKIs; including dasatinib, nilotinib, bosutinib, radotinib, and ponatinib) versus imatinib for patients with newly diagnosed chronic myeloid leukemia (CML).
SUMMARY
We identified randomized controlled trials comparing the efficacy of NG-TKIs versus imatinib as the first-line treatment for CML patients by searching the PubMed, Cochrane library, and EMBASE databases. Two reviewers independently extracted data and assessed study quality. A meta-analysis was performed to calculate risk ratios and 95% CIs using a fixed-effects model.Our study included 10 trials. Overall, treatment with NG-TKIs significantly improved the major molecular response and MR4.5 at all time points, and early molecular response at 3 months. Importantly, overall survival (OS) was significantly higher with the NG-TKIs at 12 months. Besides, NG-TKI-treated patients showed a significantly lower CML-related death and progression to the accelerated phase/blast crisis. Key Messages: In first-line treatment, NG-TKIs are superior to imatinib regarding OS at 12 months, and because molecular response rates were higher with the NG-TKIs at all time points, the NG-TKIs favor treatment-free remission.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Female; Gastrointestinal Diseases; Hematologic Diseases; Humans; Imatinib Mesylate; Leukemia, Myeloid, Chronic-Phase; Male; Middle Aged; Progression-Free Survival; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic; Survival Analysis; Young Adult
PubMed: 31514197
DOI: 10.1159/000501537 -
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 -
International Journal of Laboratory... Oct 2020Leukoerythroblastic reaction (LER) is characterized by the presence of immature erythroid cells and myeloid precursors (metamyelocytes, myelocytes, promyelocytes,... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Leukoerythroblastic reaction (LER) is characterized by the presence of immature erythroid cells and myeloid precursors (metamyelocytes, myelocytes, promyelocytes, myeloblasts, and blasts) as well as, exclusively in myelofibrotic disorders, teardrop cells in the peripheral blood (J Pathol Bacteriol, 42, 1936, 541; Semaine Med, 22, 1902, 373). Research on how to interpret LER and its meaning in clinical practice is scarce, and there is no consensus on the diagnostic criteria. We summarize the current evidence with the aim of clarifying the knowledge on this subject.
METHODS
We conducted a comprehensive search of the PubMed-MEDLINE, EMBASE and ELSEVIER databases, the Cochrane Library, Google Scholar, and medical journals to identify relevant papers.
RESULTS
Our search identified 425 papers, of which, 35 (11 trials and 24 case reports) ultimately met the inclusion criteria. These showed two principal groups of diseases associated with leukoerythroblastosis (LEB), corresponding to solid and hematological malignancies. The other etiologies, in order of frequency, were hemolytic diseases, infection, and others, while hemorrhage was only reported in the trials group.
CONCLUSION
The literature on LER is scarce and heterogeneous. The etiological factors of LER are diverse, and its presence in malignant disease is an indicator of disease progression and an adverse prognosis suggesting poor survival. In those cases where LER had neither hematological nor solid neoplasms, its manifestation, prognosis and its impact on our daily clinical practice are unknown.
Topics: Animals; Disease Management; Disease Susceptibility; Erythroid Cells; Humans; Leukocytes; Medical History Taking; Myeloproliferative Disorders
PubMed: 32562368
DOI: 10.1111/ijlh.13238 -
Acta Haematologica 2020The treatment of chronic myeloid leukaemia (CML) requires quantitative polymerase chain reaction (qPCR) to monitor BCR-ABL1 in International Scale (IS). Some normal...
The treatment of chronic myeloid leukaemia (CML) requires quantitative polymerase chain reaction (qPCR) to monitor BCR-ABL1 in International Scale (IS). Some normal subjects were found to harbour BCR-ABL1. We performed a systematic review on normal subjects harbouring BCR-ABL1. A literature search was done on July 16, 2017 using EBSCOhost Research Databases interface and Western Pacific Region Index Medicus. Two authors selected the studies, extracted the data, and evaluated the quality of studies using the modified Appraisal Tool for Cross-Sectional Studies independently. The outcomes were prevalence, level of BCR-ABL1IS, proportion, and time of progression to CML. The initial search returned 4,770 studies. Eleven studies, all having used convenient sampling, were included, with total of 1,360 subjects. Ten studies used qualitative PCR and one used qPCR (not IS). The mean prevalence of M-BCR was 5.9, 15.5, and 15.9% in cord blood/newborns/infants (CB/NB/I) (n = 170), children (n = 90), and adults (n = 454), respectively, while m-BCR was 15, 26.9, and 23.1% in CB/NB/I (n = 786), children (n = 67), and adults (n = 208), respectively. No study reported the proportion and time of progression to CML. Nine studies were graded as moderate quality, one study as poor quality, and one study as unacceptable. The result of the studies could neither be inferred to the general normal population nor compared. Follow-up data were scarce.
Topics: Acute Disease; Blast Crisis; Chronic Disease; Databases, Factual; Fusion Proteins, bcr-abl; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome
PubMed: 31401626
DOI: 10.1159/000501146 -
Clinical Lymphoma, Myeloma & Leukemia Jan 2023The prognosis and life expectancy of chronic myeloid leukemia (CML) patients have improved significantly with the launch of first tyrosine kinase inhibitor (TKI),... (Review)
Review
The prognosis and life expectancy of chronic myeloid leukemia (CML) patients have improved significantly with the launch of first tyrosine kinase inhibitor (TKI), imatinib. Maintaining at least one major molecular response in CML patients without the use of TKI is known as treatment-free remission (TFR). The safety of the first TFR (TFR1) effort has been reported by numerous studies. However, some patients relapse during TFR1. A second TFR (TFR2) can be tried again in those patients. This systematic review aims to evaluate individual patient characteristics for a TFR2, factors predicting successful TFR2, monitoring, consequences of the cessation of TKI, and studies about TFR2. We identified 5 studies related TFR2. The results showed that the first failed TKI discontinuation attempt is not an indicator of a second TKI discontinuation failure. TKIs could safely and successfully be discontinued for a second time in chronic phase CML patients despite a TFR1 failure. The most important factors for estimating TFR2 success are the speed of molecular relapse and the TKI-free duration after the first TKI discontinuation attempt. New trends in the management of CML patients are reducing the side effects of treatment, lessening the financial burden, and improving the quality of life of patients as CML has developed into a manageable chronic disease rather than an aggressive cancer. Although there are many studies and guidelines on TFR1, there are few studies on TFR2 and predictive factors. More data is still needed regarding TFR2 attempt in patients with CML.
Topics: Humans; Quality of Life; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Imatinib Mesylate; Protein Kinase Inhibitors; Recurrence
PubMed: 36344420
DOI: 10.1016/j.clml.2022.09.004 -
Platelets Oct 2021A potential relationship between poor prognosis and thrombocytosis has been suggested by previous studies in lung cancer, but the conclusions continued to be... (Meta-Analysis)
Meta-Analysis
A potential relationship between poor prognosis and thrombocytosis has been suggested by previous studies in lung cancer, but the conclusions continued to be controversial. Here, we performed a meta-analysis to explore the prognostic impact of thrombocytosis in lung cancer. The Cochrane Library, EMBASE and PubMed databases were comprehensively and systematically retrieved from establishment to May 5, 2020. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were applied to evaluate overall effects. Heterogeneity was assessed using I statistics and Cochran's Q test. Sensitivity and subgroup analyses were performed to analyze the sources of heterogeneity. Publication bias was examined using the Egger's test and pooled HR was regulated using the trim-and-fill approach when publication bias was observed. A total of 37 studies including 14,833 patients were enrolled in the meta-analysis. Thrombocytosis was significantly correlated to poor overall survival (HR 1.033; 95% CI 1.017-1.050), disease-free survival (HR 1.568; 95% CI 1.276-1.928), and progression-free survival (HR 1.653; 95% CI 1.069-2.556). Although publication bias was identified, rectification for this bias using the trim-and-fill approach did not change the combined HR substantially. In conclusion, this meta-analysis result suggested that thrombocytosis is a predictor of poor prognosis in lung cancer.
Topics: Adult; Aged; Female; Humans; Lung Neoplasms; Male; Middle Aged; Prognosis; Thrombocytosis
PubMed: 32892682
DOI: 10.1080/09537104.2020.1810653 -
Expert Review of Hematology Nov 2020Myeloproliferative neoplasms (MPNs) are a group of clonal hematopoietic stem cell disorders that may occur after one or more mutations in hematopoietic progenitor cells....
OBJECTIVE
Myeloproliferative neoplasms (MPNs) are a group of clonal hematopoietic stem cell disorders that may occur after one or more mutations in hematopoietic progenitor cells. In this study, we will review the co-existence of mutations (especially dual mutations) in MPNs and its effect on the prognosis of patients.
METHODS
To find relevant published papers, we systematically searched six major international indexing databases, namely PubMed/Medline, EmBase, Cochrane central, ISI web of science, and Scopus from Feb. 2000 until Jan. 2020. We included the following keywords in the analyzes: Myeloproliferative Disorders, Mutation, Co-existence of Mutations, Acute myeloid leukemia.
RESULTS
Co-existence of several mutations in MPNs is mainly associated with a poor prognosis compared with the unimutated MPN disorders. There are several effective factors such as sequence of mutations, incidence of mutations in one cell or different cells, mutation, and MPN type.
CONCLUSION AND EXPERT COMMENTARY
It seems that monitoring the status of mutations in MPNs and recognizing the co-existence of mutations (especially dual mutations) in order to determine prognosis and possibility of progression to acute form of leukemia can lead to the prediction of prognosis in MPN patients as well as establishment of better and more reliable therapeutic strategies for patients.
Topics: Cell Transformation, Neoplastic; Clonal Evolution; Disease Progression; Humans; Leukemia, Myeloid, Acute; Mutation; Myeloid Cells; Myeloproliferative Disorders; Neoplasm Proteins; Prognosis; Signal Transduction
PubMed: 32886563
DOI: 10.1080/17474086.2020.1819232 -
Medicine Sep 2022There is no study analyzing and evaluating the prognostic role of thrombocytosis in Asian patients with colorectal cancer (CRC). (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is no study analyzing and evaluating the prognostic role of thrombocytosis in Asian patients with colorectal cancer (CRC).
METHODS
A systematic search of articles (PubMed, Embase, and the Cochrane Library) was performed to identify studies using the terms Platelet count, Thrombocytosis, Thrombocytoses, Thrombocythemia or Thrombocythemias with colon, colonic, rectal, rectum, colorectal and prognostic, prognosis, survival or outcome.
RESULTS
Thirteen eligible studies with 3964 patients were included. Thrombocytosis was associated with a poorer overall survival (HR of 1.88 [95% CI: 1.24-2.85; P = .003] with univariate analyses, HR of 2.07 [95% CI: 1.2-3.56; P = .008] with multivariate analyses), disease-free survival (HR of 2.58 [95% CI: 1.87-3.57; P < .00001] with multivariate analyses) and cancer specific survival (HR of 2.55 [95% CI: 1.68-3.85; P < .00001]) in Asian patients with CRC. Thrombocytosis had a significant association with female gender, tumor location in the colon, higher pathological T-stage, pathological positive N-stage, but not with lymphatic involvement and venous involvement.
CONCLUSION
The present meta-analysis demonstrates that thrombocytosis is a potentially useful tool for predicting poor survival in Asian patients with CRC, especially for overall survival.
Topics: Colorectal Neoplasms; Disease-Free Survival; Female; Humans; Platelet Count; Prognosis; Thrombocytosis
PubMed: 36107503
DOI: 10.1097/MD.0000000000030275