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Clinical Rheumatology Feb 2023Cryoglobulinemic vasculitis (CV) or mixed cryoglobulinemic syndrome (MCS) is a systemic small-vessel vasculitis characterized by the proliferation of B-cell clones... (Review)
Review
Cryoglobulinemic vasculitis (CV) or mixed cryoglobulinemic syndrome (MCS) is a systemic small-vessel vasculitis characterized by the proliferation of B-cell clones producing pathogenic immune complexes, called cryoglobulins. It is often secondary to hepatitis C virus (HCV), autoimmune diseases, and hematological malignancies. CV usually has a mild benign clinical course, but severe organ damage and life-threatening manifestations can occur. Recently, evidence in favor of rituximab (RTX), an anti-CD 20 monoclonal antibody, is emerging in CV: nevertheless, questions upon the safety of this therapeutic approach, especially in HCV patients, are still being issued and universally accepted recommendations that can help physicians in MCS treatment are lacking. A Consensus Committee provided a prioritized list of research questions to perform a systematic literature review (SLR). A search was made in Medline, Embase, and Cochrane library, updated to August 2021. Of 1227 article abstracts evaluated, 27 studies were included in the SLR, of which one SLR, 4 RCTs, and 22 observational studies. Seventeen recommendations for the management of mixed cryoglobulinemia with rituximab from the Italian Study Group of Cryoglobulinemia (GISC) were developed to give a valuable tool to the physician approaching RTX treatment in CV.
Topics: Humans; Rituximab; Cryoglobulinemia; Consensus; Hepatitis C; Hepacivirus; Vasculitis
PubMed: 36169798
DOI: 10.1007/s10067-022-06391-w -
British Journal of Haematology Jun 2013Gaucher disease is an autosomal, recessively inherited, lysosomal storage disease, which has been associated with gammopathies and malignancies. This report represents... (Meta-Analysis)
Meta-Analysis Review
Gaucher disease is an autosomal, recessively inherited, lysosomal storage disease, which has been associated with gammopathies and malignancies. This report represents the results of a systematic review of the literature on the prevalence of monoclonal gammopathies and malignancies in Gaucher disease. A PubMed search identified 365 studies, of which 80 reported on concomitant Gaucher disease and malignancies and/or gammopathies (15 cohort/cross sectional studies, and 65 case reports/series). Based on these studies, we conclude that compared to the general population, Gaucher patients have an increased risk of cancer in general [pooled relative risk of 1·70 (95% confidence interval 1·27-2·31)], and multiple myeloma and haematological malignancies in particular (estimated risk between 25·0 and 51·1 and 3·5 and 12·7, respectively). In addition, an increased risk has been reported for hepatocellular carcinoma and renal cell carcinoma. Several factors have been hypothesized to play a role in the pathophysiology. These include: splenectomy, immune dysregulation, endoplasmic reticulum stress, genetic modifiers, altered iron metabolism and insulin resistance.
Topics: Gaucher Disease; Humans; Neoplasms; Paraproteinemias; Prevalence; Risk
PubMed: 23594419
DOI: 10.1111/bjh.12335 -
The Chinese Journal of Dental Research 2015To provide an overview of internal organ involvement (IOI) in immunoglobulin G4-related sialadenitis (IgG4-RS) patients, with a focus on the prevalence and clinical... (Review)
Review
OBJECTIVE
To provide an overview of internal organ involvement (IOI) in immunoglobulin G4-related sialadenitis (IgG4-RS) patients, with a focus on the prevalence and clinical features of IOI, the analysis of serum IgG4 levels in patients with or without IOI, and the usefulness of positron emission tomography (PET) for examination of the whole body.
METHODS
A systematic search was performed using PubMed, CNKI, Wanfang Data and CQVIP databases.
RESULTS
A total of 99 articles, including 493 IgG4-RS cases, were analysed in this study. The male-to-female ratio was 1.57:1 and the mean age was 61.67 years. IOI was observed in 71.6% patients, including lesions of the pancreas (38.5%), the biliary system and liver (17.8%), distant lymphadenopathy (20.3%), the respiratory system (15.6%), the urinary system (12.0%) and retroperitoneal fibrosis (11.4%). The lesions could occur homeochronously or metachronously with IgG4-RS. The serum IgG4 levels in the IOI-positive and IOI-negative groups were 1,131 ± 952 mg/dL and 659 ± 843 mg/dL, respectively (P < 0.01). The prevalence of IOI and the number of involved internal organs between the PET and the non-PET groups showed no significant difference (P = 0.399 and P = 0.823, respectively), but were significantly higher in the PET group, amongst patients whose first symptom or chief complaint was salivary gland swelling (P = 0.002 and P = 0.001, respectively).
CONCLUSION
IOI is common in IgG4-RS and almost every organ can be affected. High levels of serum IgG4 represent a potential indicator of IOI. Furthermore, PET is a useful tool for evaluation of the whole body.
Topics: Humans; Autoimmune Diseases; Immunoglobulin G; Paraproteinemias; Positron-Emission Tomography; Sialadenitis; Viscera
PubMed: 26167546
DOI: No ID Found -
Scientific Reports Jun 2016During the past decades, many novel agents have improved response and survival of patients with multiple myeloma. Nevertheless, it remains challenging when they suffer... (Meta-Analysis)
Meta-Analysis Review
During the past decades, many novel agents have improved response and survival of patients with multiple myeloma. Nevertheless, it remains challenging when they suffer relapsing. Thus, novel therapeutic agents are needed. We aimed to assess the efficacy and safety of a novel agent panobinostat for patients with relapsed or/and refractory MM. A systematic literature review identified studies for clinical trials about panobinostat in patients with relapsed or/and refractory MM. We searched studies published between January 2000 and December 2015 in Pubmed, Ovid, EBSCO and the Cochrane library. Random-effect pooled estimates were calculated for overall response rate and rates of common adverse effects. The results showed 11 clinical trials including 700 patients with relapsed or/and refractory MM treated with panobinostat were identified. The ORR varied between 0.08 and 0.67. Pooled analyses showed the results that the ORR was 0.45 (95% CI: 0.31-0.59, I(2) = 90.5%, P = 0.000) for panobinostat combined with any other kind of drugs. The most common Grade3/4 adverse effects were thrombocytopenia, neutropenia, lymphopenia, anemia, diarrhea, fatigue, nausea and so on. In conclusion, based on our analyses, the regimen of panobinostat combining with other agents seems to be well tolerated and efficacious in patients with relapsed or/and refractory MM.
Topics: Antineoplastic Agents; Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Humans; Hydroxamic Acids; Indoles; Multiple Myeloma; Panobinostat; Recurrence; Treatment Outcome
PubMed: 27270478
DOI: 10.1038/srep27361 -
BMC Cancer May 2023Upfront high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains a profitable strategy for newly diagnosed multiple myeloma (MM) patients... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Upfront high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains a profitable strategy for newly diagnosed multiple myeloma (MM) patients in the context of novel agents. However, current knowledge demonstrates a discrepancy between progression-free survival (PFS) and overall survival (OS) benefit with HDT/ASCT.
METHODS
We conducted a systematic review and meta-analysis that included both randomized controlled trials (RCTs) and observational studies evaluating the benefit of upfront HDT/ASCT published during 2012 to 2023. Further sensitivity analysis and meta-regression were also performed.
RESULTS
Among the 22 enrolled studies, 7 RCTs and 9 observational studies had a low or moderate risk of bias, while the remaining 6 observational studies had a serious risk of bias. HDT/ASCT revealed advantages in complete response (CR) with an odds ratio (OR) of 1.24 and 95% confidence interval (CI) 1.02 ~ 1.51, PFS with a hazard ratio (HR) of 0.53 (95% CI 0.46 ~ 0.62), and OS with an HR of 0.58 (95% CI 0.50 ~ 0.69). Sensitivity analysis excluding the studies with serious risk of bias and trim-and-fill imputation fundamentally confirmed these findings. Older age, increased percentage of patients with International Staging System (ISS) stage III or high-risk genetic features, decreased proteasome inhibitor (PI) or combined PI/ immunomodulatory drugs (IMiD) utilization, and decreased follow-up duration or percentage of males were significantly related to a greater survival advantage with HDT/ASCT.
CONCLUSIONS
Upfront ASCT remains a beneficial treatment for newly diagnosed MM patients in the period of novel agents. Its advantage is especially acute in high-risk MM populations, such as elderly individuals, males, those with ISS stage III or high-risk genetic features, but is attenuated with PI or combined PI/IMiD utilization, contributing to divergent survival outcomes.
Topics: Male; Humans; Aged; Multiple Myeloma; Antineoplastic Combined Chemotherapy Protocols; Hematopoietic Stem Cell Transplantation; Transplantation, Autologous; Disease-Free Survival; Stem Cell Transplantation
PubMed: 37193978
DOI: 10.1186/s12885-023-10907-1 -
Journal of Environmental Science and... 2016This systematic review and meta-analysis rigorously examines the relationship between glyphosate exposure and risk of lymphohematopoietic cancer (LHC) including NHL,... (Meta-Analysis)
Meta-Analysis
This systematic review and meta-analysis rigorously examines the relationship between glyphosate exposure and risk of lymphohematopoietic cancer (LHC) including NHL, Hodgkin lymphoma (HL), multiple myeloma (MM), and leukemia. Meta-relative risks (meta-RRs) were positive and marginally statistically significant for the association between any versus no use of glyphosate and risk of NHL (meta-RR = 1.3, 95% confidence interval (CI) = 1.0-1.6, based on six studies) and MM (meta-RR = 1.4, 95% CI = 1.0-1.9; four studies). Associations were statistically null for HL (meta-RR = 1.1, 95% CI = 0.7-1.6; two studies), leukemia (meta-RR = 1.0, 95% CI = 0.6-1.5; three studies), and NHL subtypes except B-cell lymphoma (two studies each). Bias and confounding may account for observed associations. Meta-analysis is constrained by few studies and a crude exposure metric, while the overall body of literature is methodologically limited and findings are not strong or consistent. Thus, a causal relationship has not been established between glyphosate exposure and risk of any type of LHC.
Topics: Glycine; Herbicides; Hodgkin Disease; Humans; Leukemia; Multiple Myeloma; Neoplasms; Risk Factors; Glyphosate
PubMed: 27015139
DOI: 10.1080/03601234.2016.1142748 -
The Cochrane Database of Systematic... Oct 2012Several clinical studies have compared single with tandem (also called double) autologous stem cell transplantation (ASCT) as first-line treatment in patients with... (Review)
Review
First-line tandem high-dose chemotherapy and autologous stem cell transplantation versus single high-dose chemotherapy and autologous stem cell transplantation in multiple myeloma, a systematic review of controlled studies.
BACKGROUND
Several clinical studies have compared single with tandem (also called double) autologous stem cell transplantation (ASCT) as first-line treatment in patients with symptomatic multiple myeloma (MM), one of the leading indications for ASCT worldwide.
OBJECTIVES
The present Cochrane Review compares tandem autologous stem cell transplantation (TASCT) with single autologous stem cell transplantation (SASCT) as first-line treatment in patients with symptomatic MM with respect to overall survival (OS), event-free survival (EFS), quality of life (QoL) and treatment- or transplantation-related mortality.
SEARCH METHODS
We systematically identified controlled trials published between January 1995 and May 2011 in two bibliographic databases (MEDLINE and CENTRAL) and in clinical trial registries.
SELECTION CRITERIA
One researcher screened references for controlled trials to determine eligibility for the systematic review (SR) according to pre-specified inclusion and exclusion criteria, reflecting characteristics of disease and the interventions. We required a minimal set of details to be reported for observational studies for the studies to be included.
DATA COLLECTION AND ANALYSIS
We critically evaluated eligible trials with respect to quality of design and actual performance. One researcher extracted individual trial results, which were checked by another researcher. We recapitulated the results of the individual trials in a standardised way for the SR in order to allow a systematic assessment of potential sources of bias.
MAIN RESULTS
Overall, we identified 14 controlled studies. One registered randomised controlled trial (RCT) is still recruiting patients at the time of this review and no clinical results have been published. Two registered RCTs have remained unpublished despite their termination. Publications on one RCT had been retracted. We excluded five observational studies since neither patients nor treatment regimens were sufficiently characterised to allow an assessment of potential confounding by indication. We conducted a SR of study designs, definition of endpoints, treatment regimens and baseline characteristics of patients in the five included RCTs (two full-text publications, three conference presentations) enrolling1506 patients in total. Because we identified substantial clinical and methodological heterogeneity, we refrained from conducting a formal meta-analysis.While we included only previously untreated, symptomatic patients with MM the treatment regimens differed notably with respect to acute toxicity, between trials and also between study arms. Compared to state of the art treatment standards, the treatment regimens applied in all trials have to be considered as below standard from a contemporary perspective in at least one component.Three trials were likely to have the potential of being highly biased while two RCTs had a moderate potential for bias. The observed treatment effects in the set of included trials may have been influenced by a steep decrease in compliance with the second ASCT and the concomitant selection of patients. In addition, OS data were confounded by the treatment subsequent to first-line therapy.OS was statistically significantly improved in one trial only. While EFS was prolonged in four of the five trials, the median prolongation ranged between three to 12 months, with an uncertain direction of bias in the individual trials. QoL was not reported in any study. Results concerning treatment- or transplantation-related mortality could not be adequately assessed due to substantial differences in definitions between trials and low reporting quality.
AUTHORS' CONCLUSIONS
We did not consider any study to be sufficiently informative for contemporary treatment decisions concerning the question single versus tandem ASCT in view of inherent biases. In addition, none of the trials integrated the so-called "novel agents" which are now considered standard treatment for MM. To improve the quality of future studies, sample size calculations should consider the potentially steep decrease in compliance with the second ASCT. Reporting of results of treatment- or transplantation-related mortality should clearly specify the type and number of events (the numerator) in a well-defined population (the denominator).
Topics: Adult; Aged; Antineoplastic Agents; Bone Marrow Transplantation; Combined Modality Therapy; Disease-Free Survival; Hematopoietic Stem Cell Transplantation; Humans; Middle Aged; Multiple Myeloma; Quality of Life; Randomized Controlled Trials as Topic; Transplantation, Autologous
PubMed: 23076906
DOI: 10.1002/14651858.CD004626.pub3 -
The Cochrane Database of Systematic... Mar 2015Paraproteinaemic neuropathy refers to those neuropathies associated with a monoclonal gammopathy or paraprotein. The most common of these present with a chronic,... (Review)
Review
BACKGROUND
Paraproteinaemic neuropathy refers to those neuropathies associated with a monoclonal gammopathy or paraprotein. The most common of these present with a chronic, predominantly sensory, symmetrical neuropathy, similar to chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but with relatively more sensory involvement, both clinically and neurophysiologically. The optimal treatment for neuropathies associated with IgG and IgA monoclonal gammopathy of uncertain significance is not known. This is an update of a review first published in 2007.
OBJECTIVES
To assess the effects of any treatment for IgG or IgA paraproteinaemic peripheral neuropathy.
SEARCH METHODS
On 18 January 2014 we searched the Cochrane Neuromuscular Disease Group Trials Specialized Register, CENTRAL, MEDLINE and EMBASE. We also checked bibliographies for controlled trials of treatments for IgG or IgA paraproteinaemic peripheral neuropathy. We checked clinical trials registries for ongoing studies in November 2014.
SELECTION CRITERIA
We considered for inclusion randomised controlled trials (RCTs) and quasi-RCTs using any treatment for IgG or IgA paraproteinaemic peripheral neuropathy. We excluded people with IgM paraproteins. We excluded people where the monoclonal gammopathy was considered secondary to an underlying disorder. We included participants of any age with a diagnosis of monoclonal gammopathy of uncertain significance with a paraprotein of the IgG or IgA class and a neuropathy. Included participants were not required to fulfil specific electrophysiological diagnostic criteria.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology to select studies, extract data and analyse results. One trial author provided additional data and clarification.
MAIN RESULTS
We identified one RCT, with 18 participants, that fulfilled the predetermined inclusion criteria. The trial compared plasma exchange to sham plasma exchange in participants with IgG or IgA paraproteinaemic neuropathy over a three-week follow-up period. We identified four other studies but these were not RCTs or quasi-RCTs. The included RCT did not report our predefined primary outcome measure, change in disability six months after randomisation. The trial revealed a modest benefit of plasma exchange in the weakness component of the Neuropathy Disability Score (NDS, now the Neuropathy Impairment Score); the mean improvement with plasma exchange was 17 points (95% confidence interval (CI) 5.2 to 28.8 points) versus 1 point (95% CI -7.7 to 9.7 points) in the sham exchange group at three weeks' follow-up (mean difference (MD) 16.00; 95% CI 1.37 to 30.63, low quality evidence). There was no statistically significant difference in the overall NDS (MD 18.00; 95% CI -2.03 to 38.03, low quality evidence), vibration thresholds or neurophysiological indices. Adverse events were not reported. The trial was at low risk of bias overall, although limitations of trial size and duration reduce the quality of the evidence in support of its conclusions.
AUTHORS' CONCLUSIONS
The evidence from RCTs for the treatment of IgG or IgA paraproteinaemic neuropathy is currently inadequate. More RCTs of treatments are required. These should have adequate follow-up periods and contain larger numbers of participants, perhaps through multicentre collaboration, considering the relative infrequency of this condition. Observational or open trial data provide limited support for the use of treatments such as plasma exchange, cyclophosphamide combined with prednisolone, intravenous immunoglobulin, and corticosteroids. These interventions show potential therapeutic promise but the potential benefits must be weighed against adverse effects. Their optimal use and the long-term benefits need to be considered and validated with well-designed RCTs.
Topics: Humans; Immunoglobulin A; Immunoglobulin G; Monoclonal Gammopathy of Undetermined Significance; Peripheral Nervous System Diseases; Plasma Exchange; Randomized Controlled Trials as Topic
PubMed: 25803231
DOI: 10.1002/14651858.CD005376.pub3 -
JAMA Dermatology Mar 2020Necrobiotic xanthogranuloma (NXG) is a non-Langerhans cell histiocytosis classically associated with paraproteinemia attributable to plasma-cell dyscrasias or...
IMPORTANCE
Necrobiotic xanthogranuloma (NXG) is a non-Langerhans cell histiocytosis classically associated with paraproteinemia attributable to plasma-cell dyscrasias or lymphoproliferative disorders. Despite the morbidity of NXG, the literature is limited to case reports and small studies, and diagnostic criteria are lacking.
OBJECTIVE
To evaluate the characteristics of NXG and propose diagnostic criteria.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter cross-sectional study was conducted at tertiary academic referral centers and followed by a systematic review and a consensus exercise. The multicenter cohort included patients with NXG diagnosed at the Brigham and Women's and Massachusetts General Hospitals (2000-2018), the University of Iowa Hospitals and Clinics (2000-2018), and the University of Pennsylvania Health System (2008-2018). The systematic review was conducted in 2018 and included patients with NXG identified in the Cochrane, Ovid EMBASE, PubMed, and Web of Science databases. The consensus exercise was conducted by 8 board-certified dermatologists to identify diagnostic criteria.
MAIN OUTCOMES AND MEASURES
Demographic factors, comorbidities, clinical features, and treatment response.
RESULTS
Of 235 included patients with NXG (34 from the multicenter cohort and 201 from the systematic review results), the mean (SD) age at presentation was 61.6 (14.2) years; 147 (62.6%) were female. Paraproteinemia was detected in 193 patients (82.1%), most often IgG-κ (117 patients [50.0%]). A malignant condition was detected in 59 patients (25.1%), most often multiple myeloma (33 patients [14.0%]). The overall rate of paraproteinemia and/or a malignant condition was 83.8% (197 patients). In the multicenter cohort, evolution of paraproteinemia into multiple myeloma was observed up to 5.7 years (median [range], 2.4 [0.1-5.7] years) after NXG presentation. Cutaneous lesions consisted of papules, plaques, and/or nodules, typically yellow or orange in color (113 of 187 [60.4%]) with a periorbital distribution (130 of 219 [59.3%]). The eye was the leading site of extracutaneous involvement (34 of 235 [14.5%]). In the multicenter cohort, intravenous immunoglobulin had the best treatment response rate (9 of 9 patients [100%]), followed by antimalarial drugs (4 of 5 patients [80%]), intralesional triamcinolone (6 of 8 patients [75%]), surgery (3 of 4 patients [75%]), chemotherapy (8 of 12 patients [67%]), and lenalidomide or thalidomide (5 of 8 patients [63%]). The consensus exercise yielded 2 major criteria, which were (1) clinical and (2) histopathological features consistent with NXG, and 2 minor criteria, consisting of (1) paraproteinemia, plasma-cell dyscrasia, and/or other associated lymphoproliferative disorder and (2) periorbital distribution of cutaneous lesions. In the absence of foreign body, infection, or another identifiable cause, fulfillment of both major and at least 1 minor criterion were proposed to establish the diagnosis of NXG.
CONCLUSIONS AND RELEVANCE
Necrobiotic xanthogranuloma is a multisystem disorder associated with paraproteinemia and malignant conditions. The proposed diagnostic criteria may advance clinical research and should be validated.
Topics: Aged; Cohort Studies; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Multiple Myeloma; Necrobiotic Xanthogranuloma; Paraproteinemias; Retrospective Studies
PubMed: 31940000
DOI: 10.1001/jamadermatol.2019.4221 -
PloS One 2013In recent years, a number of randomized controlled trials (RCTs) have reported on lenalidomide as a treatment for multiple myeloma (MM). Herein, we report results of a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In recent years, a number of randomized controlled trials (RCTs) have reported on lenalidomide as a treatment for multiple myeloma (MM). Herein, we report results of a meta-analysis of RCTs examining the efficacy and safety of lenalidomide for MM.
PATIENTS AND METHODS
Databases were searched using the terms "lenalidomide or revlimid AND multiple myeloma."RCTs evaluating initial or maintenance therapeutic outcomes were included. Main outcome measures were response rates, progression-free survival (PFS), overall survival, and adverse events.
RESULTS
Seven trials were included (N = 192-614 participants). Lenalidomide doses and treatment regimens differed between trials. Complete response (CR) and very good partial response (VGPR) risk ratios (RR) favored lenalidomide over placebo (CR = 2.54, 95% confidence interval [CI] = 1.29-5.02; VGPR = 2.82, 95% CI = 1.30-6.09). The PFS hazard ratio favored lenalidomide over placebo (0.37, 95% CI = 0.33-0.41). For adverse events, neutropenia, deep vein thrombosis (DVT), infection, and hematologic cancer RR favored placebo over lenalidomide (neutropenia: 4.74, 95% CI = 2.96-7.57; DVT: 2.52; 95% CI: 1.60-3.98; infection: 1.98; 95% CI: 1.50-2.62; hematologic cancer: 3.20; 95% CI: 1.28-7.98).
CONCLUSIONS
Lenalidomide is an effective treatment for MM; however, treatment-related adverse events must be considered and appropriate adjustments and/or prophylactic treatment should be initiated where possible.
Topics: Disease-Free Survival; Humans; Lenalidomide; Multiple Myeloma; Neoplasms, Second Primary; Randomized Controlled Trials as Topic; Thalidomide; Treatment Outcome
PubMed: 23691202
DOI: 10.1371/journal.pone.0064354