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Nutrients Aug 2023Acute leukemia commonly occurs in young children with peak incidence at the age of 2-5 years. However, the etiology is still unclear and many preventable risk factors... (Meta-Analysis)
Meta-Analysis Review
Acute leukemia commonly occurs in young children with peak incidence at the age of 2-5 years. However, the etiology is still unclear and many preventable risk factors still deserve to be reviewed. The focus of this systematic review and meta-analysis is to summarize the evidence concerning early life nourishment (breastfeeding, early life diet), neonatal vitamin K administration and the risk of acute leukemia. All epidemiological studies published up to June 2023 and assessing diet-related risk factors for childhood acute leukemia were identified in two electronic databases (PubMed and Web of Science), with no limits on publication year or language. A total of 38 studies (37 case-control studies and 1 study with pooled analysis) were included. The published risk estimates were combined into a meta-analysis using the Generic Inverse Variance method. The current evidence shows that breastfeeding (yes vs. no) has a protective effect against acute lymphoblastic leukemia (odds ratio = 0.85; 95% CI, 0.76-0.94). Evidence related to the role of other studied factors (foods and supplements) is inconclusive. Further research into the potential role of diet in early life and the risk of acute leukemia is needed to develop prevention strategies at population level. Review Registration: PROSPERO registration no. CRD42019128937.
Topics: Infant, Newborn; Female; Humans; Child; Child, Preschool; Leukemia, Myeloid, Acute; Nutritional Status; Breast Feeding; Case-Control Studies; Dietary Supplements
PubMed: 37686807
DOI: 10.3390/nu15173775 -
British Journal of Sports Medicine Aug 2023To estimate the dose-response associations between non-occupational physical activity and several chronic disease and mortality outcomes in the general adult population. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To estimate the dose-response associations between non-occupational physical activity and several chronic disease and mortality outcomes in the general adult population.
DESIGN
Systematic review and cohort-level dose-response meta-analysis.
DATA SOURCES
PubMed, Scopus, Web of Science and reference lists of published studies.
ELIGIBILITY CRITERIA
Prospective cohort studies with (1) general population samples >10 000 adults, (2) ≥3 physical activity categories, and (3) risk measures and CIs for all-cause mortality or incident total cardiovascular disease, coronary heart disease, stroke, heart failure, total cancer and site-specific cancers (head and neck, myeloid leukaemia, myeloma, gastric cardia, lung, liver, endometrium, colon, breast, bladder, rectum, oesophagus, prostate, kidney).
RESULTS
196 articles were included, covering 94 cohorts with >30 million participants. The evidence base was largest for all-cause mortality (50 separate results; 163 415 543 person-years, 811 616 events), and incidence of cardiovascular disease (37 results; 28 884 209 person-years, 74 757 events) and cancer (31 results; 35 500 867 person-years, 185 870 events). In general, higher activity levels were associated with lower risk of all outcomes. Differences in risk were greater between 0 and 8.75 marginal metabolic equivalent of task-hours per week (mMET-hours/week) (equivalent to the recommended 150 min/week of moderate-to-vigorous aerobic physical activity), with smaller marginal differences in risk above this level to 17.5 mMET-hours/week, beyond which additional differences were small and uncertain. Associations were stronger for all-cause (relative risk (RR) at 8.75 mMET-hours/week: 0.69, 95% CI 0.65 to 0.73) and cardiovascular disease (RR at 8.75 mMET-hours/week: 0.71, 95% CI 0.66 to 0.77) mortality than for cancer mortality (RR at 8.75 mMET-hours/week: 0.85, 95% CI 0.81 to 0.89). If all insufficiently active individuals had achieved 8.75 mMET-hours/week, 15.7% (95% CI 13.1 to 18.2) of all premature deaths would have been averted.
CONCLUSIONS
Inverse non-linear dose-response associations suggest substantial protection against a range of chronic disease outcomes from small increases in non-occupational physical activity in inactive adults. CRD42018095481.
Topics: Male; Adult; Female; Humans; Prospective Studies; Cardiovascular Diseases; Exercise; Neoplasms; Chronic Disease
PubMed: 36854652
DOI: 10.1136/bjsports-2022-105669 -
Hematology (Amsterdam, Netherlands) Dec 2023The meta-analysis sought to evaluate the efficacy and safety of a combination of venetoclax (Ven) and azacitidine (AZA) in the treatment of acute myeloid leukemia (AML)... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of venetoclax and azacytidine combination treatment in patients with acute myeloid leukemia and myelodysplastic syndrome: systematic review and meta-analysis.
OBJECTIVES
The meta-analysis sought to evaluate the efficacy and safety of a combination of venetoclax (Ven) and azacitidine (AZA) in the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
METHODS
We searched PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, and Web of Science for eligible studies from inception to June 2022. We used the Cochrane Risk of Bias 2.0 (RoB 2.0) and Methodological Index for Non-Randomized Studies (MINORS) to evaluate the quality of the included literature. The inverse variance method was used to calculate the pooled proportion and 95% confidence interval (CI).
RESULTS
The meta-analysis included nineteen studies with a total of 1615 patients. The pooled overall CR/CRi (complete response (CR)/complete response with incomplete blood count recovery (CRi)) rate for AML and MDS was 57.9% (95% CI 49.5-65.9%, I = 83%). Subgroup analyses showed that the rate of pooled CR/CRi was 67.5% (95% CI 61.1-73.3%, I = 54%) for the new-diagnosed (ND) AML group, 30% (95% CI 20-44.1%, I = 66%) for relapsed/refractory (R/R) AML, and 67.6% (95% CI 52.6-79.8%, I = 65%) for MDS, respectively. One randomized controlled trial (RCT) showed that CR/CRi was 64.7% in ND-AML patients. A total of 9 studies reported adverse events, with neutropenia being the most common of grade 3-4 adverse events, with a rate of 53.7% (95% CI 61.1-73.3%, I = 54%).
CONCLUSION
The present meta-analysis demonstrated that the Ven + AZA regimen is efficacious for the treatment of AML and MDS, with it being more effective for ND-AML than R/R AML. The most common adverse effects of this regimen are grade 3-4 neutropenia and neutropenia with fever.
Topics: Humans; Azacitidine; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Antineoplastic Combined Chemotherapy Protocols; Neutropenia
PubMed: 37036307
DOI: 10.1080/16078454.2023.2198098 -
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 -
Current Oncology (Toronto, Ont.) Aug 2023Anemia is a common problem when patients present with cancer, and it can worsen during treatment. Anemia can directly impact the cognitive and physical quality of life... (Review)
Review
Anemia is a common problem when patients present with cancer, and it can worsen during treatment. Anemia can directly impact the cognitive and physical quality of life and may impair fitness for oncological therapy. The most common cause of anemia is iron deficiency. Newer intravenous (IV) iron formulations offer a safe and rapidly effective treatment option. We performed a systematic mapping review of randomized controlled trials (RCTs) evaluating intravenous iron therapy in patients with cancer and anemia and their outcomes. A total of 23 RCTs were identified. The median number of patients enrolled was 104 (IQR: 60-134). A total of 5 were focused on surgical outcomes (4 preoperative, 1 postoperative), and 15 were in adjuvant therapies for a variety of tumor types (breast, colorectal, lung, gynecological, myeloid, and lymphomas), 10 of which were in combination with erythropoietin-stimulating agents (ESAs) therapy, 2 in radiotherapy, and 1 in palliative care. Overall, the studies reported that the use of IV iron increased hemoglobin concentration and decreased transfusion rates during different cancer treatment regimes. IV iron can be administered safely throughout the cancer treatment pathway from primary surgery to the palliative setting. More studies are needed to demonstrate net clinical outcomes.
Topics: Humans; Randomized Controlled Trials as Topic; Medical Oncology; Anemia; Iron; Combined Modality Therapy
PubMed: 37754484
DOI: 10.3390/curroncol30090569 -
BMC Cancer Aug 2023Currently, there is no standard treatment for managing relapse in patients with acute myeloid leukemia and myelodysplastic syndrome (AML/MDS) after allogeneic... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of venetoclax combined with hypomethylating agents for relapse of acute myeloid leukemia and myelodysplastic syndrome post allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis.
BACKGROUND
Currently, there is no standard treatment for managing relapse in patients with acute myeloid leukemia and myelodysplastic syndrome (AML/MDS) after allogeneic hematopoietic cell transplantation. Venetoclax-based therapies have been increasingly used for treating post-transplantation relapse of AML. The aim of this systematic review and meta-analysis was to evaluate the efficacy and adverse events of Venetoclax combined with hypomethylating agents (HMAs) for AML/MDS relapse post-transplantation.
METHODS
We searched PubMed, Web of Science, Excerpta Medica Database, Cochrane Library, and Clinical. gov for eligible studies from the inception to February 2022. The Methodological Index for Non-Randomized Studies was used to evaluate the quality of the included literatures. The inverse variance method calculated the pooled proportion and 95% confidence interval (CI).
RESULTS
This meta-analysis included 10 studies involving a total of 243 patients. The pooled complete response and complete response with incomplete blood count recovery rate of Venetoclax combined with HMAs for post-transplantation relapse in AML/MDS was 32% (95% CI, 26-39%, I = 0%), with an overall response rate of 48% (95% CI, 39-56%, I = 37%). The 6-month survival rate was 42% (95% CI, 29-55%, I = 62%) and the 1-year survival rate was 23% (95% CI, 11-38%, I = 78%).
CONCLUSION
This study demonstrated a moderate benefit of Venetoclax in combination with HMAs for patients with relapsed AML/MDS post-transplantation (including those who have received prior HMAs therapy), and may become one of treatment options in the future. Large-scale prospective studies are needed to confirm the potential benefit from venetoclax combined with HMAs.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Bridged Bicyclo Compounds, Heterocyclic; Leukemia, Myeloid, Acute; Chronic Disease; Myelodysplastic Syndromes; Neoplasms, Second Primary
PubMed: 37592239
DOI: 10.1186/s12885-023-11259-6 -
Frontiers in Medicine 2023Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus causing the coronavirus disease of 2019. The disease has caused millions of deaths since the...
INTRODUCTION
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus causing the coronavirus disease of 2019. The disease has caused millions of deaths since the first pandemic at the end of 2019. Immunocompromised individuals are more likely to develop severe infections. Numerous mutations had developed in SARS-CoV-2, resulting in strains (Alfa Beta Delta Omicron) with varying degrees of virulence disease severity. In CML (chronic myeloid leukemia) patients, there is a lot of controversy regarding the effect of the treatment on the patient outcome. Some reports suggested potential better outcomes among patients with CML, likely due to the use of TKI; other reports showed no significant effects. Additionally, it is unknown how much protection immunization provides for cancer patients.
METHOD
In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards, we conducted a systematic review. Retrospective, prospective studies, reviews, case series, and case reports of chronic myeloid leukemia patients aged above 18 years who had SARS-CoV-2 infection were included. English literature was screened using PubMed, SCOPUS, and Google Scholar. Search terms include chronic myeloid leukemia, chronic myelogenous leukemia, and SARS-CoV-2 and Coronavirus disease 2019 (COVID-19). We searched the reference lists of the included studies for any new articles. The search included all articles published up to April 20, 2023. The review is registered in PROSPERO (registration number CRD42022326674).
RESULTS
We reviewed 33 articles of available published literature up to April 2023 and collected data from a total of 682 CML patients with COVID-19. Most patients were in the chronic phase, seven were in the accelerated phase, and eight were in the blast phase. Disease severity was classified according to WHO criteria. Mortality was seen in 45 patients, and there were no reports of thrombotic events. Two hundred seventy-seven patients were in the era before vaccination; among them, eight were in the intensive care unit (ICU), and mortality was 30 (11%). There were 405 patients after the era of vaccination; among them, death was reported in 15 (4%) patients and ICU in 13 patients.
LIMITATIONS AND CONCLUSION
The major limitation of this review is the lack of details about the use or hold of TKIs during SARS-CoV-2 infection. Additionally, after the appearance of the different variants of the SARS-CoV-2 virus, few studies mentioned the variant of the virus, which makes it difficult to compare the outcome of the other variants of the SARS-CoV-2 virus in patients with CML. Despite the limitations of the study, CML patients with COVID-19 have no significant increase in mortality compared to other hematological malignancy. Hematological cancers are associated with an increased risk of thrombosis, which is expected to increase in patients with COVID-19. However, patient with CML has not been reported to have a significant increase in thrombosis risk. The available data indicates that COVID-19's effect on patients with chronic myeloid leukemia (CML) still needs to be better understood due to the limited data.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php? RecordID:326674.
PubMed: 38327268
DOI: 10.3389/fmed.2023.1280271 -
Leukemia Research Oct 2023Venetoclax (VEN) in combination with intensive chemotherapy (IC) is increasingly used to treat patients with high-risk acute myeloid leukemia (AML). We conducted a...
Safety and efficacy of FLAG-Ida-based therapy combined with venetoclax for the treatment for newly diagnosed and relapsed/refractory patients with AML - A systematic review.
Venetoclax (VEN) in combination with intensive chemotherapy (IC) is increasingly used to treat patients with high-risk acute myeloid leukemia (AML). We conducted a systematic review to assess the safety and efficacy outcomes of FLAG-IDA in combination with VEN. The primary safety outcome was infection rate; the primary efficacy outcome was response to treatment (composite complete remission (CRc) and overall response rate (ORR). Risk of bias was assessed according to the ROBINS-I tool. Six studies including 221 patients with newly-diagnosed (ND AML (n = 120)) and R/R AML (n = 101) disease, were included in this systematic review. Pooling of results was not conducted due to major differences between studies. The reported rates of neutropenic fever, bacteremia, pneumonia and invasive fungal infections were at 44-55 %, 24-48 %, 12-30 % and 11-36 % of assessed patients, respectively. Time to ANC and platelet recovery ranged between 23 and 29 and 23-31 days, respectively. Early death rate was 8.7 % (14/160) patients: four patients at 30 days, additional ten in 60 days. CRc rates ranged between 53 % and 78 % for R/R AML. CRc for ND was reported by one study only (89 %). ORR were reported in 60-78 % of patients with R/R AML. Only one study reported an ORR for ND patients of 98 %. In our systematic review, FLAG-Ida plus VEN proved to be a potentially tolerable and effective regimen in ND and R/R AML patients. We suggest further evaluation and confirmation for the safety and efficacy of this new protocol in future RCTs.
Topics: Humans; Idarubicin; Leukemia, Myeloid, Acute; Cytarabine; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic
PubMed: 37598660
DOI: 10.1016/j.leukres.2023.107368 -
Cancers Sep 2023In recent years, the association of venetoclax (VEN) with hypomethylating agents (HMAs) significantly improved the outcome of patients with newly diagnosed acute myeloid... (Review)
Review
In recent years, the association of venetoclax (VEN) with hypomethylating agents (HMAs) significantly improved the outcome of patients with newly diagnosed acute myeloid leukemia (AML) who were unfit for intensive chemotherapy and became the standard of care after the publication of the pivotal RCT VIALE-A. However, it is still not clear to what extent the results observed in the VIALE-A apply to a real-world setting. For this reason, we carried out a systematic review and meta-analysis of real-world studies on newly diagnosed patients with AML, ineligible for intensive induction chemotherapy, receiving first-line VEN+HMA. We then compared their results in term of survival with those from the VIALE-A. Kaplan-Meier curves were extracted from all included studies and individual survival data was reconstructed. We then estimated a pooled survival curve and compared it with the results of the VIALE-A using the log-rank test. We also conducted a secondary analysis including only studies considering VEN plus azacytidine (AZA) as treatment, as this was the schedule originally used in the VIALE-A. Nineteen real-world studies met the inclusion criteria and were included in the systematic review. Most of them reported a worse survival than the VIALE-A. The pooled survival curve was similar to that reported in the VIALE-A during the first three months of treatment but diverged thereafter (-value = 0.0001). The pooled median survival among the real-world studies was 9.37 months (95%CI 8.81-10.5), substantially lower than that reported in the VIALE-A (14.7 months; 95%CI 11.9-18.7). Results slightly increased when the analysis was restricted to the studies using VEN+AZA as treatment (median survival: 11.5 months; 95%CI 10.2-14.8). Survival of newly diagnosed AML patients treated with VEN+HMAs in a real-world setting seems to be lower than previously reported in the VIALE-A, while the effect of VEN+AZA is more in line with expected results. Future studies are needed to evaluate whether this apparent discrepancy is due to the different characteristics of enrolled patients or to a non-optimal adherence to therapy, and whether alternative regimens can provide better results in terms of safety and effectiveness.
PubMed: 37760587
DOI: 10.3390/cancers15184618 -
Cancer Oct 2023Acute myeloid leukemia (AML) has been considered an oncologic emergency that requires initiation of chemotherapy immediately after diagnosis. With the introduction of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute myeloid leukemia (AML) has been considered an oncologic emergency that requires initiation of chemotherapy immediately after diagnosis. With the introduction of novel targeted therapies, there is a potential benefit associated with delaying definitive treatment for identification of actionable therapeutic targets. Unfortunately, cytogenetic/molecular testing can take >7 days to return, and there is not a consensus regarding the prognostic impact of time from diagnosis to treatment (TDT) in AML.
METHODS
A literature review and meta-analysis of studies done to date that evaluate TDT was conducted. Studies that reported baseline characteristics, TDT, and outcomes for patients with AML were selected. Outcomes included overall survival (OS), complete remission (CR), and mortality. Studies that measured CR rates within each TDT range and data to calculate odds ratios were included in the meta-analysis. The remaining outcomes were synthesized descriptively for literature review.
RESULTS
Thirteen studies were identified, which comprised a total of 14,946 patients. Median TDT values were between 1 and 8 days. Several studies found a significant association between prolonged TDT and older age and lower proliferation burden. Four of 11 studies did not detect a significant relationship between TDT and OS. No studies found a significant association between TDT and early death. Six of eight studies did not find a significant association between TDT and CR rate. The meta-analysis found a significant association between prolonged TDT and decreased achievement of CR (p < .05).
CONCLUSIONS
Results were highly variable but suggest it may be feasible to pursue cytogenetic/molecular testing in patients who are clinically stable, particularly in those aged 60 years and older.
Topics: Humans; Middle Aged; Aged; Prognosis; Leukemia, Myeloid, Acute; Remission Induction
PubMed: 37254580
DOI: 10.1002/cncr.34894