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Medicine Nov 2023There have been controversial findings from recent studies regarding anthracyclines use and the subsequent risk of arrhythmias. This study aimed to evaluate the existing... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There have been controversial findings from recent studies regarding anthracyclines use and the subsequent risk of arrhythmias. This study aimed to evaluate the existing evidence of the risk of arrhythmias in patients treated with anthracyclines.
METHODS
PubMed, Scopus, and Web of Science databases were searched up to April 2022 using keywords such as "anthracycline" and "arrhythmia." Dichotomous data were presented as relative risk (RR) and confidence interval (CI), while continuous data were presented as mean difference (MD) and CI. Revman software version 5.4 was used for the analysis.
RESULTS
Thirteen studies were included with a total of 26891 subjects. Pooled analysis showed that anthracyclines therapy was significantly associated with a higher risk of arrhythmia (RR: 1.58; 95% CI: 1.41-1.76; P < .00001), ST segment and T wave abnormalities (RR: 1.73, 95% CI: 1.18-2.55, P = .005), conduction abnormalities and AV block (RR = 1.86, 95% CI = 1.06-3.25, P = .03), and tachycardia (RR: 1.736, 95% CI: 1.11-2.69, P = .02). Further analyses of the associations between anthracyclines and atrial flutter (RR = 1.30, 95% CI = 0.29-5.89, P = .74), atrial ectopic beats (RR: 1.27, 95% CI: 0.78-2.05, P = .34), and ventricular ectopic beats (RR: 0.93, 95% CI: 0.53-1.65, P = .81) showed no statistically significant results. Higher doses of anthracycline were associated with a higher risk of arrhythmias (RR: 1.49; 95% CI: 1.08-2.05; P = .02) compared to the lower doses (RR: 1.36; 95% CI: 1.00-1.85; P = .05). Newer generations of Anthracycline maintained the arrhythmogenic properties of previous generations, such as Doxorubicin.
CONCLUSION
Anthracyclines therapy was significantly associated with an increased risk of arrhythmias. Accordingly, Patients treated with anthracyclines should be screened for ECG abnormalities and these drugs should be avoided in patients susceptible to arrhythmia. The potential benefit of the administration of prophylactic anti-fibrotic and anti-arrhythmic drugs should also be explored.
Topics: Humans; Anthracyclines; Arrhythmias, Cardiac; Antibiotics, Antineoplastic; Doxorubicin; Tachycardia; Leukemia, Myeloid, Acute
PubMed: 37986405
DOI: 10.1097/MD.0000000000035770 -
Frontiers in Immunology 2023We conducted a systematic review and meta-analysis to evaluate outcomes following chimeric antigen receptor T cell (CAR-T) therapy in relapsed/refractory acute myeloid... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We conducted a systematic review and meta-analysis to evaluate outcomes following chimeric antigen receptor T cell (CAR-T) therapy in relapsed/refractory acute myeloid leukemia (RR-AML).
METHODS
We performed a literature search on PubMed, Cochrane Library, and Clinicaltrials.gov. After screening 677 manuscripts, 13 studies were included. Data was extracted following PRISMA guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed.
RESULTS
We analyzed 57 patients from 10 clinical trials and 3 case reports. The pooled complete and overall response rates were 49.5% (95% CI 0.18-0.81, I=65%) and 65.2% (95% CI 0.36-0.91, I=57%). The pooled incidence of cytokine release syndrome, immune-effector cell associated neurotoxicity syndrome, and graft-versus-host disease was estimated as 54.4% (95% CI 0.17-0.90, I=77%), 3.9% (95% CI 0.00-0.19, I=22%), and 1.6% (95%CI 0.00-0.21, I=33%), respectively.
CONCLUSION
CAR-T therapy has demonstrated modest efficacy in RR-AML. Major challenges include heterogeneous disease biology, lack of a unique targetable antigen, and immune exhaustion.
Topics: Humans; Receptors, Chimeric Antigen; Antigens, CD19; Immunotherapy, Adoptive; Leukemia, Myeloid, Acute; Cell- and Tissue-Based Therapy
PubMed: 37168849
DOI: 10.3389/fimmu.2023.1152457 -
Blood Reviews Nov 2023Despite recent advancements, treatment of cytopenia due to bone marrow failures (BMF) and myeloid neoplasms remains challenging. Androgens promote renewal and maturation... (Review)
Review
Despite recent advancements, treatment of cytopenia due to bone marrow failures (BMF) and myeloid neoplasms remains challenging. Androgens promote renewal and maturation of blood cells and may be beneficial in these forms. Here we report a systematic review of androgens use as single agent in hematologic conditions. Forty-six studies, mainly retrospective with various androgen types and doses, were included: 12 on acquired aplastic anemia (AA), 11 on inherited BMF, 17 on myelodysplastic syndromes (MDS), and 7 on myelofibrosis. Responses ranged from 50 to 70% in inherited BMF, 40-50% in acquired AA and MDS, while very limited evidence emerged for myelofibrosis. In acquired AA, response was associated with presence of non-severe disease; in MDS androgens were more effective on thrombocytopenia or mild to moderate anemia, whilst limited benefit was observed for transfusion dependent anemia. Toxicity profile mainly consisted of virilization and liver enzyme elevation, whilst the risk of leukemic evolution remains controversial.
Topics: Humans; Androgens; Primary Myelofibrosis; Retrospective Studies; Neoplasms; Anemia, Aplastic; Myelodysplastic Syndromes; Bone Marrow Failure Disorders; Pancytopenia; Myeloproliferative Disorders; Thrombocytopenia
PubMed: 37709654
DOI: 10.1016/j.blre.2023.101132 -
Genes Aug 2023PSTPIP1 (proline-serine-threonine phosphatase-interactive protein 1)-associated myeloid-related proteinemia inflammatory (PAMI) syndrome, previously known as... (Review)
Review
PSTPIP1 (proline-serine-threonine phosphatase-interactive protein 1)-associated myeloid-related proteinemia inflammatory (PAMI) syndrome, previously known as Hyperzincemia/Hypercalprotectinemia (Hz/Hc) syndrome, is a recently described, rare auto-inflammatory disorder caused by specific deleterious variants in the gene (p.E250K and p.E257K). The disease is characterized by chronic systemic inflammation, cutaneous and osteoarticular manifestations, hepatosplenomegaly, anemia, and neutropenia. Increased blood levels of MRP 8/14 and zinc distinguish this condition from other PSTPIP1-associated inflammatory diseases (PAID). The aim of this systematic review is to provide a comprehensive overview of the disease phenotype, course, treatment, and outcome based on reported cases. This systematic review adheres to the PRISMA guidelines (2020) for reporting. A literature search was performed in Embase, Medline, and Web of Science on 13 October 2022. The quality of the case reports and case series was assessed using the JBI checklists. Out of the 43 included patients with PAMI syndrome, there were 24 females and 19 males. The median age at onset was 3.9 years. The main clinical manifestations included anemia (100%), neutropenia (98%), cutaneous manifestations (74%), osteoarticular manifestations (72%), splenomegaly (70%), growth failure (57%), fever (51%), hepatomegaly (56%), and lymphadenopathy (39%). Systemic inflammation was described in all patients. Marked elevation of zinc and MRP 8/14 blood levels were observed in all tested patients. Response to treatment varied and no consistently effective therapy was identified. The most common therapeutic options were corticosteroids (N = 30), anakinra (N = 13), cyclosporine A (N = 11), canakinumab (N = 6), and anti-TNF (N = 14). Hematopoietic stem cell transplantation has been recently reported to be successful in five patients. Our review highlights the key characteristics of PAMI syndrome and the importance of considering this disease in the differential diagnosis of patients presenting with early-onset systemic inflammation and cytopenia.
Topics: Female; Male; Humans; Tumor Necrosis Factor Inhibitors; Neutropenia; Diagnosis, Differential; Cytoskeletal Proteins; Adaptor Proteins, Signal Transducing
PubMed: 37628706
DOI: 10.3390/genes14081655 -
Oncology 2023Therapy-related leukemia is a term that describes the occurrence of leukemia following exposure to hematotoxins and radiation to emphasize the difference from leukemia... (Review)
Review
BACKGROUND
Therapy-related leukemia is a term that describes the occurrence of leukemia following exposure to hematotoxins and radiation to emphasize the difference from leukemia that arises de novo. Many agents and host factors contribute to this entity of leukemias. Therapy-related acute myeloid leukemia has an extensive literature review in contrast to therapy-related chronic myeloid leukemia (t-CML). Radioactive iodine (RAI), an established agent in the management of differentiated thyroid carcinomas, has raised concern due to its possible carcinogenic effects.
SUMMARY
In this article, we reviewed all the reports from the 1960s to date related to t-CML following RAI on Google Scholar and PubMed. We have identified 14 reports and found that most reports were for men under the age of 60 years with primary papillary thyroid carcinoma and mixed follicular-papillary thyroid carcinoma who developed t-CML mainly between 4 and 7 years after exposure to varying doses of I131. However, the mean dose was 287.78 millicuries (mCi). It was reported that a statistically significant increase in leukemia following RAI therapy (relative risk of 2.5 for I131 vs. no I131). Also, there was a linear relationship between the cumulative dose of I131 and the risk of leukemia. Doses higher than 100 mCi were associated with a greater risk of developing secondary leukemia, and most of the leukemias developed within the initial 10 years of exposure. The precise mechanism through which RAI provokes leukemia is largely unclear. A few mechanisms have been proposed.
KEY MESSAGES
Although the risk for t-CML appears to be low based on current reports and does not represent a contraindication to RAI therapy, it should not be disregarded. We suggest including it in the risk-benefit discussion before initiating this therapy. Long-term follow-up for patients is advisable for those who received doses over 100 mCi with a complete blood count, possibly yearly, for the first 10 years. The new onset of significant leukocytosis post RAI exposure should raise the suspicion for t-CML. Further studies are needed to establish or refute a causal relationship.
Topics: Male; Humans; Middle Aged; Thyroid Neoplasms; Iodine Radioisotopes; Thyroid Cancer, Papillary; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Risk Assessment
PubMed: 37231874
DOI: 10.1159/000530463 -
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 -
The Cochrane Database of Systematic... Feb 2016Malignant neoplasms of the lymphoid or myeloid cell lines including lymphoma, leukaemia and myeloma are referred to as haematological malignancies. Complementary and... (Review)
Review
BACKGROUND
Malignant neoplasms of the lymphoid or myeloid cell lines including lymphoma, leukaemia and myeloma are referred to as haematological malignancies. Complementary and alternative treatment options such as meditation practice or yoga are becoming popular by treating all aspects of the disease including physical and psychological symptoms. However, there is still unclear evidence about meditation's effectiveness, and how its practice affects the lives of haematologically-diseased patients.
OBJECTIVES
This review aims to assess the benefits and harms of meditation practice as an additional treatment to standard care for adults with haematological malignancies.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 8, 2015), MEDLINE (1950 to August 2015), databases of ongoing trials, the metaRegister of Controlled Trials (mRCT) (http://www.controlled-trials.com/mrct/), conference proceedings of annual meetings of: the American Society of Hematology; American Society of Clinical Oncology; European Hematology Association; European Congress for Integrative Medicine; and Global Advances in Health and Medicine (2010 to 2015).
SELECTION CRITERIA
We included randomised controlled trials (RCTs) using meditation practice for adult patients with haematological malignancies.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data from eligible studies and assessed the risk of bias according to predefined criteria. We evaluated quality of life and depression. The other outcomes of overall survival, anxiety, fatigue, quality of sleep and adverse events could not be evaluated, because they were not assessed in the included trial.
MAIN RESULTS
We included only one small trial published as an abstract article. The included study investigated the effects of meditation practice on patients newly hospitalised with acute leukaemia. Ninety-one participants enrolled in the study, but only 42 participants remained in the trial throughout the six-month follow-up period and were eligible for analysis. There was no information provided about the average age and sex of the study population. We found a high risk for attrition bias and unclear risk for reporting bias, performance and detection bias because of missing data due to abstract publication only, thus we judged the overall risk of bias as high. According to the GRADE criteria, we judged the overall quality of the body of evidence for all predefined outcomes as 'very low', due to the extent of missing data on the study population, and the small sample size.As the abstract publication did not provide numbers and results except P values, we are not able to give more details.Meditation practice might be beneficial for the quality of life of haematologically-diseased patients, with higher scores for participants in the mediation arms compared to the participants in the usual care control group (low quality of evidence). Levels of depression decreased for those practising meditation in both the spiritually-framed meditation group and the secularly-focused meditation group in comparison to the usual care control group, whose levels of depression remained constant (low quality of evidence). The influence of meditation practice on overall survival, fatigue, anxiety, quality of sleep and adverse events remained unclear, as these outcomes were not evaluated in the included trial.
AUTHORS' CONCLUSIONS
To estimate the effects of meditation practice for patients suffering from haematological malignancies, more high quality randomised controlled trials are needed. At present there is not enough information available on the effects of meditation in haematologically-diseased patients to draw any conclusion.
Topics: Acute Disease; Adult; Depression; Hematologic Neoplasms; Humans; Leukemia; Meditation; Randomized Controlled Trials as Topic
PubMed: 26840029
DOI: 10.1002/14651858.CD011157.pub2 -
Clinical Epigenetics Jul 2023To systematically evaluate the efficacy and safety of FDA-approved isocitrate dehydrogenase (IDH) inhibitors in the treatment of IDH-mutated acute myeloid leukemia (AML). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically evaluate the efficacy and safety of FDA-approved isocitrate dehydrogenase (IDH) inhibitors in the treatment of IDH-mutated acute myeloid leukemia (AML).
METHODS
We used R software to conduct a meta-analysis of prospective clinical trials of IDH inhibitors in the treatment of IDH-mutated AML published in PubMed, Embase, Clinical Trials, Cochrane Library and Web of Science from inception to November 15th, 2022.
RESULTS
A total of 1109 IDH-mutated AML patients from 10 articles (11 cohorts) were included in our meta-analysis. The CR rate, ORR rate, 2-year survival (OS) rate and 2-year event-free survival (EFS) rate of newly diagnosed IDH-mutated AML (715 patients) were 47%, 65%, 45% and 29%, respectively. The CR rate, ORR rate, 2-year OS rate, median OS and median EFS of relapsed or refractory (R/R) IDH-mutated AML (394 patients) were 21%, 40%, 15%, 8.21 months and 4.73 months, respectively. Gastrointestinal adverse events were the most frequently occurring all-grade adverse events and hematologic adverse events were the most frequently occurring ≥ grade 3 adverse events.
CONCLUSION
IDH inhibitor is a promising treatment for R/R AML patients with IDH mutations. For patients with newly diagnosed IDH-mutated AML, IDH inhibitors may not be optimal therapeutic agents due to low CR rates. The safety of IDH inhibitors is controllable, but physicians should always pay attention to and manage the differentiation syndrome adverse events caused by IDH inhibitors. The above conclusions need more large samples and high-quality RCTs in the future to verify.
Topics: Humans; Prospective Studies; DNA Methylation; Leukemia, Myeloid, Acute; Enzyme Inhibitors; Mutation
PubMed: 37434249
DOI: 10.1186/s13148-023-01529-2 -
Therapeutic Advances in Gastroenterology 2023Long-term management of inflammatory bowel diseases (IBD) is challenging and the identification of reliable predictors for treatment outcomes is an unmet need.... (Review)
Review
BACKGROUND
Long-term management of inflammatory bowel diseases (IBD) is challenging and the identification of reliable predictors for treatment outcomes is an unmet need. Neutrophil-related biomarkers have been mainly studied in the feces, but blood analyses have inherent advantages.
OBJECTIVE
To review the recent learnings on the ability of blood-based neutrophil-expressed biomarkers to predict treatment outcomes in IBD.
DESIGN
Systematic scoping review.
DATA SOURCES AND METHODS
We performed a literature search in Pubmed, EMBASE, SCOPUS, Web of Science, ScienceDirect, and Cochrane Central Register of Controlled Trials from inception until May 2022 according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. All human studies associating blood-based neutrophil-related compounds with the prediction of disease progression, complication onset, or treatment outcomes were included.
RESULTS
From 1032 retrieved entries, 34 studies were selected, 32 published in 2013 or later. In all, 17 biomarkers from granules, cytoplasm, plasmatic membrane, and plasma were explored. In total, 1850 Crohn's disease (CD) and 1122 ulcerative colitis non-duplicated patients were included. The most mentioned biomarkers were nCD64, serum calprotectin (SC), oncostatin M (OSM), neutrophil elastase-generated calprotectin fragment (CPa9-HNE), and triggering receptor expressed on myeloid cells 1 (TREM1). Six biomarkers showed promising results: OSM, SC, eNAMPT, nCD64, TREM1, and CPa9-HNE. Variable positive signals were found for human neutrophil peptide 1-3, LL-37, S100A12, and neutrophil gelatinase-associated lipocalin. No predictive ability was found for the remaining markers. Sharing a neutrophil compartment did not indicate similar behavior.
CONCLUSION
Advances in the last decade began to unveil the untapped potential of the readily accessible blood neutrophil-expressed biomarkers, especially nCD64, TREM1, and CPa9-HNE. Current evidence suggests that future research should focus on well-defined subpopulations instead of a one-size-fits-all biomarker.
REGISTRATION
https://osf.io/kes9a.
PubMed: 36923488
DOI: 10.1177/17562848231155987 -
Occupational and Environmental Medicine Sep 2020Recent evidence has accumulated that the immune system is intimately intertwined with cancer development. Two key characteristics of carcinogens in which the immune... (Review)
Review
OBJECTIVE
Recent evidence has accumulated that the immune system is intimately intertwined with cancer development. Two key characteristics of carcinogens in which the immune system plays a central role are chronic inflammation and immunosuppression. In this systematic review, we investigated the association of chronic inflammatory and immunosuppressive outcomes with benzene, a widely used industrial chemical. Benzene has been confirmed to cause acute myeloid leukaemia and suspected to cause non-Hodgkin lymphoma, two cancers of the blood-forming system that affect immune cells.
METHODS
We systematically searched PubMed and Embase for all relevant studies using a combination of Medical Subject Headings (MeSH) and selected key words. The detailed review protocol, including search strategy, was registered with PROSPERO, the international prospective register of systematic reviews (#CRD42019138611).
RESULTS
Based on all human studies selected in the final review, we report new evidence of a benzene-induced immunosuppressive effect on the immune system and activation of the immune system to cause inflammation. In particular, benzene significantly lowers the number of white blood cells, particularly lymphocytes such as CD4 T-cells, B-cells and natural killer cells, and increases proinflammatory biomarkers at low levels of exposure.
CONCLUSION
To the best of our knowledge, this is the first comprehensive review of benzene's immunotoxicity in humans. Based on results obtained from this review, we propose two potential immunotoxic mechanisms of how benzene induces leukaemia/lymphoma: (1) cancer invasion caused by proinflammatory cytokine production, and (2) cancer promotion via impaired immunosurveillance. Further studies will be required to confirm the connection between benzene exposure and its effects on the immune system.
PubMed: 32938756
DOI: 10.1136/oemed-2020-106517