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Bone Marrow Transplantation May 2023Cardiovascular diseases are an emerging cause of mortality and morbidity in survivors of hematopoietic stem cell transplantation (HSCT); however, the incidence of... (Meta-Analysis)
Meta-Analysis Review
Cardiovascular diseases are an emerging cause of mortality and morbidity in survivors of hematopoietic stem cell transplantation (HSCT); however, the incidence of cardiovascular events (CVEs) in this population is not well described. This systematic review summarizes the evidence on the incidence of CVEs in HSCT recipients. Medline and Embase were searched from inception to December 2020. Inclusion criteria were cohort studies and phase 3 randomized controlled trials that reported CVEs among adults who underwent HSCT for hematological malignancies. After reviewing 8386 citations, 57 studies were included. The incidence of CVEs at 100 days was 0.19 (95% CI: 0.17-0.21) per 100 person-days after autologous HSCT and 0.06 (95% CI: 0.05-0.07) per 100 person-days after allogeneic HSCT. This higher incidence after autologous HSCT was driven by reports of arrhythmia from one population-based study in patients with multiple myeloma. The incidence of long-term CVEs was 3.98 (95% CI; 3.44-4.63) per 1000 person-years in survivors of autologous HSCT and 3.06 (95% CI; 2.69-3.48) per 1000 person-years in survivors of allogeneic HSCT. CVEs remain an important but under-reported cause of morbidity and mortality in recipients of HSCT. Future studies are required to better understand the incidence and risk factors for CVEs in HSCT recipients.
Topics: Adult; Humans; Hematopoietic Stem Cell Transplantation; Transplantation, Autologous; Cohort Studies; Risk Factors; Cardiovascular Diseases
PubMed: 36849807
DOI: 10.1038/s41409-023-01928-2 -
Journal of Cancer Survivorship :... Apr 2023The purpose of this systematic review with meta-analysis was to evaluate the safety, feasibility and effectiveness of exercise in the palliative care phase for people... (Meta-Analysis)
Meta-Analysis
PURPOSE
The purpose of this systematic review with meta-analysis was to evaluate the safety, feasibility and effectiveness of exercise in the palliative care phase for people with advanced cancer.
METHODS
Electronic databases were searched for exercise randomised controlled trials involving individuals with incurable cancer that were published prior to April 14, 2021. Meta-analyses were performed to evaluate the effects of exercise on health outcomes. Subgroup effects for exercise mode, supervision, intervention duration and cancer diagnosis were assessed.
RESULTS
Twenty-two trials involving interventions ranging between 2 weeks and 6 months were included. Interventions comprised of aerobic (n = 3), resistance (n = 4), mixed-mode (n = 14) and other exercise (n = 1) modalities. Cancer types consisted of lung (n = 6), breast (n = 3), prostate (n = 2), multiple myeloma (n = 1) and mixed cancer types (n = 10). Meta-analysis of 20 RCTs involving 1840 participants showed no difference in the risk of a grade 2-4 adverse event between exercise and usual care (n = 110 adverse events (exercise: n = 66 events; usual care: n = 44 events), RD = - 0.01 (91% CI = - 0.01, 0.02); p = 0.24). Overall median recruitment, retention and adherence rates were 56%, 80% and 69%, respectively. Meta-analysis of health outcomes showed effects in favour of exercise for quality of life, fatigue, aerobic fitness and lower-body strength (SMD range = 0.27-0.48, all p < 0.05).
CONCLUSIONS
Participants who engaged in exercise experienced an increase in quality of life, fitness and strength and a decrease in fatigue.
IMPLICATIONS FOR CANCER SURVIVORS
Physical activity programs were found to be safe and feasible for people with advanced cancer in the palliative care phase.
Topics: Male; Humans; Quality of Life; Palliative Care; Cancer Survivors; Neoplasms; Exercise; Fatigue
PubMed: 35040076
DOI: 10.1007/s11764-021-01153-0 -
Journal of Clinical Medicine Jul 2022The involvement of the larynx in plasma cell myeloma (PCM) may manifest as solitary extramedullary plasmacytoma of the larynx (sEMP-L) or as infiltration of the larynx...
Solitary Extramedullary Plasmacytoma of the Larynx and Secondary Laryngeal Involvement in Plasma Cell Myeloma: Single-Centre Retrospective Analysis and Systematic Literature Review.
The involvement of the larynx in plasma cell myeloma (PCM) may manifest as solitary extramedullary plasmacytoma of the larynx (sEMP-L) or as infiltration of the larynx during newly diagnosed or relapsed systemic disease with bone marrow involvement (plasma cell myeloma with laryngeal involvement, PCM-L). To increase knowledge about these rare conditions, we performed a retrospective analysis along with a comprehensive literature review of cases of sEMP-L or PCM-L. Six patients (two sEMP-L and four PCM-L) were identified in our tertiary laryngological centre from 2009 to 2021, constituting 0.88% of all malignant laryngeal tumours. The literature search yielded 187 cases, including 152 sEMP-L and 35 sPCM-L. A comparison of baseline characteristics between sEMP-L and PCM-L performed in the combined cohort of cases from literature review and retrospective analysis revealed that patients with sEMP-L were younger (56 vs. 64 years, ≤ 0.001) and presented less commonly with thyroid or cricoid cartilage involvement (2.2% vs. 30.8%, ≤ 0.001). The prognosis of sEMP-L was better than PCM-L (overall survival 86% vs. 55% at 5 years, = 0.002). Analysis of potential factors that could influence progression-free survival (PFS) in the group of sEMP-L revealed that male sex and cartilage involvement negatively affected PFS in univariate analyses, while only cartilage involvement retained statistical significance in multivariate analysis (HR = 19.94, = 0.024). In conclusion, PCM with laryngeal involvement is sporadic. Secondary involvement of the larynx during PCM might be more common than sEMP-L and is associated with worse survival. The involvement of cartilage adversely influences the outcome of sEMP-L.
PubMed: 35956004
DOI: 10.3390/jcm11154390 -
Technology and Health Care : Official... 2023Currently, the frequency of coagulation dysfunction associated with chimeric antigen receptor-T cell (Car-T) therapy cannot yet be determined. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Currently, the frequency of coagulation dysfunction associated with chimeric antigen receptor-T cell (Car-T) therapy cannot yet be determined.
OBJECTIVE
We performed a systematic review and meta-analysis to examine the prevalence of abnormal laboratory tests related to coagulation disorders in patients receiving Car-T therapy and provide a reference for future risk assessment mechanisms.
METHODS
We searched PubMed, Embase, and Web of Science for relevant studies and evaluated their quality using the methodology index of non-random research (MINORS). 2672 quotations were retrieved via systematic searches. After screening of titles, abstracts and full-text, 45 trials involving 2541 patients were ultimately included. 41 studies reported the incidence of thrombocytopenia, 8 studies reported the rate of low fibrin, 4 trials reported the rate of APTT or PT abnormalities and only 3 trials reported the incidence of venous thromboembolism (VTE). We performed a quantitative meta-analysis to explore the incidence of thrombocytopenia following Car-T treatment. The incidence of hypofibrinogenemia, VTE, and abnormal APTT or PT was only qualitatively assessed, as fewer reports were included in this study.
RESULTS
The overall incidence of thrombocytopenia associated with Car-T therapy was 45.8% (95%[CI], 0.384-0.533). The highest rates of thrombocytopenia occurred in patients with multiple myeloma (60.1%, 95%[CI], 0.507-0.688) and aged between 18 to 60 (50%, 95%[CI], 0.367-0.633). There was greater prevalence of thrombocytopenia in BCMA-Car-T therapy of 58.7% (95%[CI], 0.482-0.685). Thrombocytopenia occurred most frequently in Car-T patients treated with a dosage of 1 × 105-1 × 106 cell/kg, at a rate of 66.2% (95%[CI], 0.561-0.749).
CONCLUSION
Overall, 45.8 percent of patients receiving Car-T treatment suffered from thrombocytopenia. Multiple myeloma patients, ages between 18-60, a dose of 1 × 105-1 × 106 cell/kg and BCMA-Car-T therapy are all considered high-risk factors.
Topics: Humans; Adolescent; Young Adult; Adult; Middle Aged; Receptors, Chimeric Antigen; Multiple Myeloma; B-Cell Maturation Antigen; Venous Thromboembolism; Hematologic Neoplasms; Blood Coagulation Disorders; Risk Factors; Thrombocytopenia; Cell- and Tissue-Based Therapy
PubMed: 37545264
DOI: 10.3233/THC-220537 -
Cancer Cell International Nov 2021High-dose melphalan (HDMEL, 200 mg/m) is considered as the standard conditioning regimen for autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple... (Review)
Review
Long-term outcomes of busulfan plus melphalan-based versus melphalan 200 mg/m conditioning regimens for autologous hematopoietic stem cell transplantation in patients with multiple myeloma: a systematic review and meta-analysis.
BACKGROUND
High-dose melphalan (HDMEL, 200 mg/m) is considered as the standard conditioning regimen for autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM). However, whether the combination of melphalan with busulfan (BUMEL) conditioning outperforms HDMEL remains controversy. Accordingly, a systematic review and meta-analysis was carried out to compare the outcomes of HDMEL and BUMEL-based conditioning regimens in newly diagnosed MM patients having undergone auto-HSCT.
METHODS
A systematic literature search was conducted in PubMed, Embase and Cochrane Library database until July 31, 2021, to identify all eligible studies comparing progression-free survival (PFS), overall survival (OS), optimal treatment response after auto-HSCT, duration of stem cell engraftment and incidence of toxic events between patients undergoing BUMEL-based and HDMEL conditioning regimens. Hazard ratio (HR), mean difference (MD) or odds ratio (OR) corresponding to 95% confidence interval (CI) were determined to estimate outcomes applying RevMan 5.4 software. Publication biases were assessed by performing Egger's test and Begg's test by Stata 15 software.
RESULTS
Ten studies with a total of 2855 MM patients were covered in the current meta-analysis. The results of this study demonstrated that patients having received BUMEL-based regimen was correlated with longer PFS (HR 0.77; 95% CI 0.67~0.89, P = 0.0002) but similar OS (HR 1.08; 95% CI 0.92~1.26, P = 0.35) compared with those having received HDMEL. The differences of best treatment response after auto-HSCT and duration of neutrophil or platelet engraftment did not have statistical significance between the two groups of patients. With respect to adverse effects, the patients in BUMEL-based group were less frequently subject to gastrointestinal toxicity while the patients in HDMEL group less often experienced mucositis and infection. No significant difference was observed in hepatic toxicity between the two groups of patients.
CONCLUSIONS
In the present study, BUMEL-based conditioning was identified as a favorable regimen for a better PFS and equivalent OS as compared with HDMEL, which should be balanced against higher incidences of mucositis and infection. BUMEL-based conditioning is likely to act as an alternative strategy to more effectively improve auto-HSCT outcomes in MM.
PubMed: 34758834
DOI: 10.1186/s12935-021-02313-z -
Blood Cancer Journal Sep 2023Rituximab-based chemo-immunotherapy is currently the standard first-line treatment for Waldenstrom macroglobulinaemia (WM), while ibrutinib has emerged as an... (Meta-Analysis)
Meta-Analysis
Rituximab-based chemo-immunotherapy is currently the standard first-line treatment for Waldenstrom macroglobulinaemia (WM), while ibrutinib has emerged as an alternative. In the absence of randomised trials (RCTs) comparing these regimens, the optimal first-line treatment for WM remains uncertain. In this systematic review and meta-analysis, we sought to assess the efficacy and safety of first-line treatment regimens for WM. We searched key databases from January 2007 to March 2023, including phase II and III trials, including treatment-naïve WM patients treated with rituximab-based regimens or ibrutinib. Response rates, progression-free survival (PFS), overall survival (OS), and toxicities were evaluated. Four phase III and seven phase II trials were included among 736 unique records. Pooled response rates from all comparative and non-comparative trials were 46%, 33% and 26% for bendamustine rituximab (BR), bortezomib-dexamethasone, cyclophosphamide, rituximab (BDRC) and ibrutinib rituximab (IR), respectively. Two-year pooled PFS was 89%, 81% and 82% with BR, BDRC and IR, respectively. Neuropathy was more frequent with bortezomib, while haematologic and cardiac toxicities were more common with chemo-immunotherapy and ibrutinib-based regimens respectively. Our findings suggest that BR yields higher response rates than bortezomib or ibrutinib-based combinations. RCTs comparing BR against emerging therapies, including novel Bruton Tyrosine Kinase Inhibitors, are warranted.
Topics: Humans; Waldenstrom Macroglobulinemia; Rituximab; Bortezomib; Clinical Protocols; Cyclophosphamide
PubMed: 37679351
DOI: 10.1038/s41408-023-00916-5 -
Cancers May 2023Quality pharmacological treatment can improve survival in many types of cancer. Drug repurposing offers advantages in comparison with traditional drug development... (Review)
Review
Quality pharmacological treatment can improve survival in many types of cancer. Drug repurposing offers advantages in comparison with traditional drug development procedures, reducing time and risk. This systematic review identified the most recent randomized controlled clinical trials that focus on drug repurposing in oncology. We found that only a few clinical trials were placebo-controlled or standard-of-care-alone-controlled. Metformin has been studied for potential use in various types of cancer, including prostate, lung, and pancreatic cancer. Other studies assessed the possible use of the antiparasitic agent mebendazole in colorectal cancer and of propranolol in multiple myeloma or, when combined with etodolac, in breast cancer. We were able to identify trials that study the potential use of known antineoplastics in other non-oncological conditions, such as imatinib for severe coronavirus disease in 2019 or a study protocol aiming to assess the possible repurposing of leuprolide for Alzheimer's disease. Major limitations of these clinical trials were the small sample size, the high clinical heterogeneity of the participants regarding the stage of the neoplastic disease, and the lack of accounting for multimorbidity and other baseline clinical characteristics. Drug repurposing possibilities in oncology must be carefully examined with well-designed trials, considering factors that could influence prognosis.
PubMed: 37296934
DOI: 10.3390/cancers15112972 -
Molecular Diagnosis & Therapy May 2023MicroRNA-155 has been discussed as a biomarker in cancer diagnosis and prognosis. Although relevant studies have been published, the role of microRNA-155 remains... (Meta-Analysis)
Meta-Analysis
BACKGROUND
MicroRNA-155 has been discussed as a biomarker in cancer diagnosis and prognosis. Although relevant studies have been published, the role of microRNA-155 remains uncertain because of insufficient data.
METHODS
We conducted a literature search in PubMed, Embase, and Web of Science databases to obtain relevant articles and extract data to evaluate the role of microRNA-155 in cancer diagnosis and prognosis.
RESULTS
The pooled results showed that microRNA-155 presented a remarkable diagnostic value in cancers (area under the curve = 0.90, 95% confidence interval (CI 0.87-0.92; sensitivity = 0.83, 95% CI 0.79-0.87; specificity = 0.83, 95% CI 0.80-0.86), which was maintained in the subgroups stratified by ethnicity (Asian and Caucasian), cancer types (breast cancer, lung cancer, hepatocellular carcinoma, leukemia, and pancreatic ductal adenocarcinoma), sample types (plasma, serum, tissue), and sample size (n >100 and n <100). In prognosis, a combined hazard ratio (HR) showed that microRNA-155 was significantly associated with poor overall survival (HR = 1.38, 95% CI 1.25-1.54) and recurrence-free survival (HR = 2.13, 95% CI 1.65-2.76), and was boundary significant with poor progression-free survival (HR = 1.20, 95% CI 1.00-1.44), but not significant with disease-free survival (HR = 1.14, 95% CI 0.70-1.85). Subgroup analyses in overall survival showed that microRNA-155 was associated with poor overall survival in the subgroups stratified by ethnicity and sample size. However, the significant association was maintained in cancer types subgroups of leukemia, lung cancer, and oral squamous cell carcinoma, but not in colorectal cancer, hepatocellular carcinoma, and breast cancer, and was maintained in sample types subgroups of bone marrow and tissue, but not in plasma and serum.
CONCLUSIONS
Results from this meta-analysis demonstrated that microRNA-155 was a valuable biomarker in cancer diagnosis and prognosis.
Topics: Humans; Female; MicroRNAs; Carcinoma, Hepatocellular; Prognosis; Carcinoma, Squamous Cell; Mouth Neoplasms; Pancreatic Neoplasms; Lung Neoplasms; Breast Neoplasms; Leukemia; Liver Neoplasms; Biomarkers, Tumor
PubMed: 36939982
DOI: 10.1007/s40291-023-00641-6 -
Seminars in Thrombosis and Hemostasis Jul 2021Bleeding and thrombosis are well-known complications to hematological malignancies, and changes in fibrinolysis impact both these issues. In the present systematic...
Bleeding and thrombosis are well-known complications to hematological malignancies, and changes in fibrinolysis impact both these issues. In the present systematic review, we provide an overview and discussion of the current literature in regards to clinical manifestations, diagnosis, and treatment of altered fibrinolysis in patients suffering from hematological malignancies, beyond acute promyelocytic leukemia. We performed a systematic literature search employing the databases Pubmed, Embase, and Web of Science to identify original studies investigating fibrinolysis in hematological malignancies. Studies investigating fibrinolysis in acute promyelocytic leukemia or disseminated intravascular coagulation were excluded. We identified 32 studies fulfilling the inclusion criteria. A majority of the studies were published more than two decades ago, and none of the studies examined all available markers of fibrinolysis or used dynamic clot lysis assays. In acute leukemia L-asparaginase treatment induced a hypofibrinolytic state, and prior to chemotherapy there seemed to be little to no change in fibrinolysis. In studies examining fibrinolysis during chemotherapy results were ambiguous. Two studies examining multiple myeloma indicated hypofibrinolysis prior to chemotherapy, and in another plasma cell disease, amyloid light chain-amyloidosis, clear signs of hyperfibrinolysis were demonstrated. In myeloproliferative neoplasms, the studies reported signs of hypofibrinolysis, in line with the increased risk of thrombosis in this disease. Only one study regarding lymphoma was identified, which indicated no alterations in fibrinolysis. In conclusion, this systematic review demonstrated that only sparse, and mainly old, evidence exists on fibrinolysis in hematological malignancy. However, the published studies showed a tendency toward hypofibrinolysis in myeloproliferative disorders, an increased risk of hyperfibrinolysis, and bleeding in patients with AL-amyloidosis, whereas studies regarding acute leukemias were inconclusive except with regard to L-asparaginase treatment, which induced a hypofibrinolytic state.
Topics: Amyloidosis; Asparaginase; Blood Coagulation Disorders; Fibrinolysis; Hematologic Neoplasms; Hemorrhage; Humans; Leukemia, Promyelocytic, Acute; Thrombosis
PubMed: 34058766
DOI: 10.1055/s-0041-1725099 -
Translational Cancer Research Mar 2022Multiple myeloma (MM) is a malignant tumor originating from plasma cells in the bone marrow. The existing treatment methods can prolong the survival time of patients,...
Efficacy and safety of chimeric antigen receptor (CAR)-T cell therapy in the treatment of relapsed and refractory multiple myeloma: a systematic-review and meta-analysis of clinical trials.
BACKGROUND
Multiple myeloma (MM) is a malignant tumor originating from plasma cells in the bone marrow. The existing treatment methods can prolong the survival time of patients, but they still face the problems of myeloma relapse and refractory disease. Chimeric antigen receptor (CAR)-T cell therapy is a new cellular immunotherapy that can target and recognize antigens and kill tumor cells but the efficacy and safety data varied in different studies. We performed this systematic review and meta-analysis to understand its efficacy and safety.
METHODS
Literature published from January 2015 to November 2021 was obtained by searching the keywords "CAR-T", "CAR-T Cell", and "Multiple Myeloma" by computer using the Embase, PubMed, Web of Science, and Cochrane library databases according to the PICOS (Participants, Interventions, Comparisons, Outcomes, Study type) criteria. The quality of the literature was assessed by the Joanna Briggs Institute (JBI) Critical Appraisal Tool for prevalence studies. The complete response rate, the incidence of cytokine release syndrome (CRS) above grade 3, and the overall incidence of adverse reactions were used as the outcome indicators. The pooled rates were performed and analyzed using the R language toolkit.
RESULTS
A total of 10 studies including 353 study cases were included. Meta-analysis showed that the pooled complete response rate of CAR-T therapy in the treatment of MM was 0.55, 95% confidence interval (CI): (0.50, 0.60), the pooled incidence of CRS was 0.55, 95% CI: (0.50, 0.60), and the pooled incidence of serious adverse reactions was 0.92, 95% CI: (0.88, 0.95). Subgroup analysis was performed based on antigen types or costimulatory molecules, and there was no significant difference in the efficacy of CAR-T and the incidence of CRS between the two subgroups (P>0.05).
CONCLUSIONS
As a new immunotherapy strategy with great potential, CAR-T has a significant effect in the treatment of MM, but its safety needs to be further improved. The types of costimulatory molecules and CAR-T antigens can affect its efficacy and safety.
PubMed: 35402175
DOI: 10.21037/tcr-22-344