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Current Oncology (Toronto, Ont.) Mar 2023Inflammatory proteins activate platelets, which have been observed to be directly related to cancer progression and development. The aim of this systematic review is to... (Review)
Review
Inflammatory proteins activate platelets, which have been observed to be directly related to cancer progression and development. The aim of this systematic review is to investigate the possible association between Mean Platelet Volume (MPV) and cancer (diagnostic capacity of MPV, relation to survival, the severity of the disease, and metastasis). A literature review was performed in the online database PubMed and Google Scholar for the period of 2010-2022. In total, 83 studies including 21,034 participants with 12 different types of cancer (i.e., gastric cancer, colon cancer, esophageal squamous cell carcinoma, renal cancer, breast cancer, ovarian cancer, endometrial cancer, thyroid cancer, lung cancer, bladder cancer, gallbladder cancer, and multiple myeloma) were identified. The role of MPV has been extensively investigated in several types of cancer, such as gastric, colon, breast, and lung cancer, while few data exist for other types, such as renal, gallbladder cancer, and multiple myeloma. Most studies in gastric, breast, endometrium, thyroid, and lung cancer documented an elevated MPV in cancer patients. Data were less clear-cut for esophageal, ovarian, and colon cancer, while reduced MPV was observed in renal cell carcinoma and gallbladder cancer. Several studies on colon cancer (4 out of 6) and fewer on lung cancer (4 out of 10) indicated an unfavorable role of increased MPV regarding mortality. As far as other cancer types are concerned, fewer studies were conducted. MPV can be used as a potential biomarker in cancer diagnosis and could be a useful tool for the optimization of treatment strategies. Possible underlying mechanisms between cancer and MPV are discussed. However, further studies are needed to elucidate the exact role of MPV in cancer progression and metastasis.
Topics: Female; Humans; Mean Platelet Volume; Gallbladder Neoplasms; Esophageal Neoplasms; Multiple Myeloma; Esophageal Squamous Cell Carcinoma; Lung Neoplasms; Colonic Neoplasms
PubMed: 36975471
DOI: 10.3390/curroncol30030258 -
American Journal of Hematology Jul 2022Bruton tyrosine kinase inhibitors (BTKi) are important treatment options in Waldenström's macroglobulinemia (WM). Whether second-generation BTKi are associated with... (Meta-Analysis)
Meta-Analysis
Bruton tyrosine kinase inhibitors (BTKi) are important treatment options in Waldenström's macroglobulinemia (WM). Whether second-generation BTKi are associated with improved outcomes and/or better safety profile remains unclear. We did a systematic review and meta-analysis of clinical trials that reported data on the outcomes of patients with WM who received either first- or second-generation BTKi in the period between January 2010 and August 2021. Studies with twenty or fewer patients were excluded. The primary outcomes were efficacy measured by response and survival data. Eleven studies met the eligibility criteria and were included in the final analysis (n = 730 patients). A total of 298 patients received 1st-generation BTKi and 432 received a 2nd-generation BTKi. Pooled overall response rate (ORR) and major response rate (MRR) for both generations were similar (94.2% and 78.5% in 1st vs. 88.9% and 75.1% in 2nd, respectively). MRR for both generations was higher in MYD88 Mut/CXCR4 WT patients compared to MYD88 Mut/CXCR4 Mut patients (odds ratio [OR]: 3.9, 95% CI: 2.2 to 5.5). Pooled 18-mo progression-free survival (PFS) was similar for both generations (88.5% vs. 87.3%). Grade 3/4 atrial fibrillation was higher in 1st-generation BTKi (3.1% vs. 0.4%); however, grade-3/-4 infections and neutropenia were more frequent in 2nd-generarion BTKi (20.9% vs. 13.2%, 17.7% vs. 12%, respectively). The efficacy of 1st- and 2nd-generation BTKis is comparable. The 1st-generation BTKi were associated with a higher risk of atrial fibrillation, whereas infections and neutropenia occurred more frequently in 2nd-generation BTKi.
Topics: Atrial Fibrillation; Humans; Lymphoma, B-Cell; Mutation; Myeloid Differentiation Factor 88; Neutropenia; Protein Kinase Inhibitors; Pyrimidines; Waldenstrom Macroglobulinemia
PubMed: 35358350
DOI: 10.1002/ajh.26552 -
British Journal of Haematology Mar 2006The activity of thalidomide in relapsed or refractory multiple myeloma is widely accepted but not yet demonstrated in a randomised-controlled trial. A systematic review... (Review)
Review
The activity of thalidomide in relapsed or refractory multiple myeloma is widely accepted but not yet demonstrated in a randomised-controlled trial. A systematic review of the published clinical trials of these patients could reduce the possible bias of single phase-II studies. A systematic search identified 42 communications reporting on 1674 patients. Thirty-two trials used an escalating dosing regimen and four a fixed dose regimen (one dose with 50 mg/d, three doses with 200 mg/d). The target dose in the dose escalating trials was 800 mg/d in 17 trials, 400-600 mg/d in 10 and 200 mg/d in one trial. The intention-to-treat population for efficacy was 1629 patients with a median age of 62 years. The complete and partial (>50% reduction in monoclonal protein) response rate was 29.4% (95%-confidence interval, 27-32%). The rates for minor responses or stable disease were 13.8% (12-16%) and 11.0% (9-13%). Progressive disease was reported in 9.9% (8-11%). The median overall survival from all trials was reported at 14 months. Severe adverse events (grade III-IV) included somnolence 11%, constipation 16%, neuropathy 6%, rash 3%, thrombo-embolism 3%, cardiac 2%. In conclusion, thalidomide monotherapy achieved complete and partial responses in 29.4% of patients with relapsed or refractory multiple myeloma.
Topics: Clinical Trials, Phase II as Topic; Data Collection; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Immunosuppressive Agents; Multiple Myeloma; Neoplasm Recurrence, Local; Peripheral Nervous System Diseases; Survival Rate; Thalidomide; Treatment Outcome
PubMed: 16445831
DOI: 10.1111/j.1365-2141.2005.05914.x -
The Cochrane Database of Systematic... 2003Early stage multiple myeloma (MM) represents about 20% of MM. Most of the patients are asymptomatic. Thus, it is far less dramatic than advanced disease and may require... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Early stage multiple myeloma (MM) represents about 20% of MM. Most of the patients are asymptomatic. Thus, it is far less dramatic than advanced disease and may require different treatment strategies. For these patients, it is not clear whether it is better to start chemotherapy right after the diagnosis or to delay the treatment until symptoms become obvious as the disease progresses.
OBJECTIVES
To identify and synthesize all available research evidence on whether early treatment intervention results in improved clinical outcomes when compared with observation alone. The main outcomes of interest that were examined included mortality, disease progression, response rate, and toxicity of early treatment.
SEARCH STRATEGY
Searches of the following electronic databases were undertaken: MEDLINE, EMBASE, CANCERLIT, LILLIACS and Cochrane Database of RCTs. We have recently compiled a comprehensive database of RCTs in myeloma. This search was updated and supplemented by hand-search of abstracts from main society meetings such as the ASH (American Society of Hematology), ASCO (American Society of Clinical Oncology), and EHA (European Haematology Association). In addition, we compared our list with a list of RCTs maintained by the Oxford Clinical Trial Service Unit.
SELECTION CRITERIA
Randomized controlled trials (RCT) with a parallel design that compared early versus deferred treatment of patients with early stage multiple myeloma based on Durie-Salmon (D-S) staging system. We also considered those trials that did not define early stage myeloma according to D-S staging system, but enrolled patients according to clinical uncertainty about the benefits of immediate intervention.
DATA COLLECTION AND ANALYSIS
Data synthesis was performed for all studies and according to the defined quality criteria. The first reviewer and the contact reviewer of this proposal independently extracted data. Disagreement was resolved by consensus. Revman software (ver 4.1) was used to combine results from all studies and expressed as an overall odds ratio or Peto's Odds Ratio, with 95% confidence interval.
MAIN RESULTS
Three trials were included with a total of 131 patients in each of the early treatment and deferred treatment groups. Early MM is asymptomatic stage I in these trials. All trials used standard Melphalan treatment but not stem cell transplantation. No statistically significant heterogeneity among the studies was detected. Beneficial effects of early treatment were seen in delay of myeloma progression (Peto's OR = 0.16, 95% CI: 0.09-0.29), and reduced vertebral compression (OR = 0.18, 95%CI: 0.02-1.59, NNT = 23, 95% CI: an NNT of 11, via infinity, to an NNH of 50). No significant effects on mortality and response rate were seen (Peto's OR = 1.11, 95% CI: 0.67-1.84, and OR = 0.63, 95% CI: 0.33-1.23, respectively). Early treatment may increase the risk of acute leukemia (Peto's OR = 3.20, 95% CI: 0.55-18.73, NNH = 44, 95% CI: an NNT of 63, via infinity, to an NNH of 15).
REVIEWER'S CONCLUSIONS
Early treatment of early stage multiple myeloma inhibits disease progression, and may reduce vertebral compression. However, early treatment may increase the risk of acute leukemia. However, the data on vertebral compression and leukaemic transformation may not be interpretable due to very small numbers. Based on the current evidence, mortality and response rate are not significantly affected by introducing early treatment in the progression of myeloma. However, it is quite possible that the lack of beneficial effects of early intervention in myeloma is a false negative result due to the paucity of the existing evidence. In addition, data on quality of life and toxicity were sparsely reported adding to additional difficulties about management decisions in early stage myeloma.
Topics: Disease Progression; Humans; Multiple Myeloma; Randomized Controlled Trials as Topic; Time Factors
PubMed: 12535504
DOI: 10.1002/14651858.CD004023 -
Critical Reviews in Oncology/hematology May 2018Standard induction therapy for multiple myeloma is three-drug combination based on following classes of drugs: proteasome inhibitors, immunomodulators and steroids.... (Review)
Review
Standard induction therapy for multiple myeloma is three-drug combination based on following classes of drugs: proteasome inhibitors, immunomodulators and steroids. Despite its notable efficacy, bortezomib has side effects like peripheral neuropathy (PNP) with reported incidence of grade ≥3 PNP between 2%-23% Schlafer et al., 2017. Carfilzomib (CFZ) has high selectivity and minimal off-target adverse effects including lower rates of PNP. CFZ is already approved for treatment of relapsed and refractory multiple myeloma (RRMM) as single agent as well as in combination with lenalidomide and/or dexamethasone. Extensive literature search identified a total of 1839 articles. Twenty-six articles (n = 5980) met the inclusion criteria, 15 in newly diagnosed multiple myeloma (NDMM) and 11 in RRMM group. CFZ demonstrates comparable or even better efficacy to bortezomib with much favorable AE profile. Deep, rapid and sustainable response using KRd with safer toxicity profile supports extension of KRd therapy to frontline therapy for all risk categories of MM. High incidence of grade ≥3 HTN underscores the importance of serial BP monitoring. In RRMM, CFZ has documented efficacy with standard 20-27mg/m2 dose. Further large-scale trials are needed to study benefit-to-risk profile of 20-56 and 20-70 mg/m2 dose of CFZ vs standard 20-27 mg/m2 dose in NDMM and RRMM.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Dexamethasone; Drug Resistance, Neoplasm; Humans; Lenalidomide; Multiple Myeloma; Oligopeptides; Proteasome Inhibitors; Thalidomide; Treatment Outcome
PubMed: 29650268
DOI: 10.1016/j.critrevonc.2018.02.008 -
Annals of Oncology : Official Journal... Apr 2007The objective of this systematic review is to examine the feasibility and safety of autologous noncryopreserved stem-cell transplants. This technique avoids the cost of... (Review)
Review
The objective of this systematic review is to examine the feasibility and safety of autologous noncryopreserved stem-cell transplants. This technique avoids the cost of establishing and maintaining a cryopreservation facility and may be of value for transplant centers in regions with limited economic resources. The primary outcome was the graft failure rate. In addition, a detailed description of the high-dose therapy regimens employed was undertaken. Secondary outcomes were transplant-related mortality and neutrophil and platelet engraftments times. Sixteen well-conducted nonrandomized studies met the eligibility criteria. Only two cases of graft failure (0.36%) occurred among 560 assessable patients receiving high-dose therapy and autotransplant for non-Hodgkin's lymphoma, Hodgkin's lymphoma, multiple myeloma, germ-cell tumors and acute leukemias. The most traditional high-dose schedules were used, although often modified to shorter regimens. High-dose melphalan appeared especially useful given its short half-life and was used to treat multiple myeloma by most groups. Secondary outcomes were comparable to those reported in the most relevant studies addressing standard (cryopreserved) autotransplant. According to this study, the use of autologous noncryopreserved hematopoietic progenitors to support patients undergoing high-dose therapy is feasible and safe.
Topics: Bone Marrow Transplantation; Cryopreservation; Humans; Leukemia; Lymphoma; Multiple Myeloma; Peripheral Blood Stem Cell Transplantation; Transplantation, Autologous
PubMed: 17355952
DOI: 10.1093/annonc/mdm069 -
Cancer Apr 2012The goal of this study was to conduct a comparative analysis of whole body X-ray (WBXR) and (18) F-fluoro-deoxyglucose positron emission tomography ((18) FDG PET) in... (Comparative Study)
Comparative Study Review
BACKGROUND
The goal of this study was to conduct a comparative analysis of whole body X-ray (WBXR) and (18) F-fluoro-deoxyglucose positron emission tomography ((18) FDG PET) in staging and response assessment of multiple myeloma.
METHODS
We performed a systematic review of studies comparing (18) FDG PET with WBXR and/or magnetic resonance imaging in terms of sensitivity for myeloma-related bone disease at staging and during follow-up.
RESULTS
Eighteen studies involving 798 patients met the inclusion criteria. The mean Quality Assessment of Diagnostic Accuracy Studies (QUADAS) score, expressed as a percentage of the maximum score, was 61%. In 7 studies (n = 242 patients), concordance assessment between WBXR and (18) FDG PET scan was possible, showing a higher sensitivity of the (18) FDG PET in the detection of myeloma bone lesions in 6 studies. The only study reporting on the prognostic value of (18) FDG PET at staging found that the number of FDG-avid focal lesions was an independent prognostic parameter. In addition, the limited studies on response monitoring showed that normalization of (18) FDG PET during treatment correlated with a superior clinical outcome.
CONCLUSIONS
In general, (18) FDG PET has a superior sensitivity for myeloma bone lesions compared with WBXR. Future studies have to validate the additive value of myeloma-related bone disease detected on (18) FDG PET-computed tomography (CT) in predicting outcome. Response monitoring with the use of (18) FDG PET-CT during treatment is promising, allowing more precise prediction of prognosis compared with the standard response monitoring. In view of the expanding treatment options for multiple myeloma, this may provide important information for treatment decisions in the future.
Topics: Bone Neoplasms; Fluorodeoxyglucose F18; Humans; Magnetic Resonance Imaging; Multiple Myeloma; Positron-Emission Tomography; Radiopharmaceuticals; Sensitivity and Specificity; Whole-Body Irradiation
PubMed: 21887677
DOI: 10.1002/cncr.26467 -
Clinical Lymphoma, Myeloma & Leukemia Jun 2023This systematic literature review (SLR) was conducted to better understand the impact of disease progression, line of therapy, and clinical response on health-related... (Review)
Review
This systematic literature review (SLR) was conducted to better understand the impact of disease progression, line of therapy, and clinical response on health-related quality of life (HRQoL) in patients with multiple myeloma (MM). Multiple databases were searched to identify records relating to HRQoL in adult patients with MM. Titles and abstracts were independently screened by 2 reviewers for inclusion based on pre-defined criteria. Records flagged for inclusion had full texts subsequently screened using the same method. A third round of screening was then conducted to identify studies that assessed the relationship of HRQoL to disease progression, line of therapy, or clinical response. Quality assessment was conducted on utility studies using the National Institute for Health and Care Excellence Quality Assessment Checklist for Health State Utility Values. After all rounds of screening were complete, 44 records (representing 41 studies) were included in the SLR. Thirty records reported data relating HRQoL to disease progression, 5 reported data relating HRQoL to line of therapy, and 19 reported data relating HRQoL to response. Despite a lack of homogeneity and small number of studies, the data show overall that progressive disease and increasing lines of therapy were associated with worsened patient HRQoL and increasing depth of response was associated with improved patient HRQoL. The findings from this SLR support that desirable treatment outcomes such as delayed progression, fewer lines of therapy, and achieving the deepest possible clinical response result in improved HRQoL in patients with MM.
Topics: Humans; Multiple Myeloma; Quality of Life; Treatment Outcome; Disease Progression
PubMed: 37061416
DOI: 10.1016/j.clml.2023.03.005 -
BMJ Open Jan 2024Multiple myeloma (MM) is a malignant plasma cell disorder. The most widely accepted staging system for MM is the revised International Staging System based on... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Multiple myeloma (MM) is a malignant plasma cell disorder. The most widely accepted staging system for MM is the revised International Staging System based on cytogenetic and clinical biomarkers. The circulating clonal plasma cells (CPCs) were reported to have potential prognostic impact on MM. Among various diagnostic approaches, multiparametric flow cytometry (FCM) offers heightened sensitivity, minimal invasiveness and reproducibility. We conducted a meta-analysis to evaluate the prognostic value of quantifying CPCs via FCM in newly diagnosed symptomatic MM (NDMM) patients.
DESIGN
Systematic review and meta-analysis.
DATA SOURCE
PubMed, Web of Science, Embase and references of included studies.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
We included observational studies that evaluated the prognostic value of CPCs detected by FCM in NDMM.
DATA EXTRACTION AND SYNTHESIS
Data were screened and extracted independently by two investigators. The pooled results originated from random effects models. The primary endpoint was overall survival (OS). The secondary endpoint was progression-free survival (PFS). To evaluate the prognostic value of CPCs in NDMM, HRs and their 95% CI for both OS and PFS were derived using COX multivariable models. These values were then used to compute the pooled estimated effect.
RESULTS
Our meta-analysis encompassed a total of 2704 NDMM patients from 11 studies up to 27 August 2022. The pooled HR for OS and PFS in CPC-positive (CPCs+) group and CPC-negative group were 1.95 (95% CI 1.24 to 3.07) and 2.07 (95% CI 1.79 to 2.39), respectively. The autologous stem cell transplantation (ASCT) failed to eliminate the adverse impact on OS and PFS. The heterogeneity may stem from the use of novel agents or traditional chemotherapy as initial treatment.
CONCLUSION
This meta-analysis indicates CPCs+ had an adverse impact on the prognosis of NDMM patients in the total population, and the adverse impact could not be eliminated by ASCT.
PROSPERO REGISTRATION NUMBER
CRD42021272381.
Topics: Humans; Multiple Myeloma; Prognosis; Plasma Cells; Flow Cytometry; Hematopoietic Stem Cell Transplantation; Reproducibility of Results; Transplantation, Autologous
PubMed: 38216195
DOI: 10.1136/bmjopen-2022-071548 -
International Archives of Allergy and... 2023Intravenous immunoglobulin (IVIg), which is used to treat multiple neurological conditions, may be associated with serious adverse reactions. The individual neurological... (Review)
Review
Intravenous immunoglobulin (IVIg), which is used to treat multiple neurological conditions, may be associated with serious adverse reactions. The individual neurological disease characteristics associated with adverse reactions, along with strategies to prevent and treat adverse reactions, are uncertain. A systematic review was conducted of the databases PubMed, Embase, and Cochrane Library to summarise studies that report adverse reactions of IVIg therapy in patients with neurological disease. There were 65 studies included in the review. The reported rates of adverse reactions vary widely, but the best evidence suggests rates between 25 and 34% per patient. Common adverse reactions include headache and laboratory abnormalities. Less common but serious adverse reactions included thromboembolic complications and anaphylaxis. Overall, there is a lack of high-quality comparative data to definitively determine if any specific neurological indications are associated with a higher risk of adverse reactions. However, individual neurological disease characteristics possibly associated with an increased likelihood of adverse reactions include limited mobility (as in certain neuromuscular conditions), paraproteinaemia (as in certain peripheral neuropathies), and cardiomyopathy (as in certain myopathies). There is limited evidence to support the effectiveness of prevention and treatment strategies, which may include modification to dose, reduced infusion rate, and premedication. Further studies regarding methods to prevent and treat IVIg-ARs in neurology patients are required.
Topics: Humans; Immunoglobulins, Intravenous; Peripheral Nervous System Diseases; Nervous System Diseases; Anaphylaxis
PubMed: 37015212
DOI: 10.1159/000529110