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The Cochrane Database of Systematic... Jan 2020Renal vasculitis presents as rapidly progressive glomerulonephritis and comprises of a group of conditions characterised by acute kidney injury (AKI), haematuria and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Renal vasculitis presents as rapidly progressive glomerulonephritis and comprises of a group of conditions characterised by acute kidney injury (AKI), haematuria and proteinuria. Treatment of these conditions involve the use of steroid and non-steroid agents in combination with plasma exchange. Although immunosuppression overall has been very successful in treatment of these conditions, many questions remain unanswered in terms of dose and duration of therapy, the use of plasma exchange and the role of new therapies. This 2019 publication is an update of a review first published in 2008 and updated in 2015.
OBJECTIVES
To evaluate the benefits and harms of any intervention used for the treatment of renal vasculitis in adults.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 21 November 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
Randomised controlled trials investigating any intervention for the treatment of renal vasculitis in adults.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as risk ratio (RR) with 95% confidence intervals (CI) for dichotomous outcomes or mean difference (MD) for continuous outcomes.
MAIN RESULTS
Forty studies (3764 patients) were included. Studies conducted earlier tended to have a higher risk of bias due to poor (or poorly reported) study design, broad inclusion criteria, less well developed disease definitions and low patient numbers. Later studies tend to have improved in all areas of quality, aided by the development of large international study groups. Induction therapy: Plasma exchange as adjunctive therapy may reduce the need for dialysis at three (2 studies: RR 0.43, 95% CI 0.23 to 0.78; I = 0%) and 12 months (6 studies: RR 0.45, 95% CI 0.29 to 0.72; I = 0%) (low certainty evidence). Plasma exchange may make little or no difference to death, serum creatinine (SCr), sustained remission or to serious or the total number of adverse events. Plasma exchange may increase the number of serious infections (5 studies: RR 1.26, 95% CI 1.03 to 1.54; I = 0%; low certainty evidence). Remission rates for pulse versus continuous cyclophosphamide (CPA) were equivalent but pulse treatment may increase the risk of relapse (4 studies: RR 1.79, 95% CI 1.11 to 2.87; I = 0%) (low certainty evidence) compared with continuous cyclophosphamide. Pulse CPA may make little or no difference to death at final follow-up, or SCr at any time point. More patients required dialysis in the pulse CPA group. Leukopenia was less common with pulse treatment; however, nausea was more common. Rituximab compared to CPA probably makes little or no difference to death, remission, relapse, severe adverse events, serious infections, or severe adverse events. Kidney function and dialysis were not reported. A single study reported no difference in the number of deaths, need for dialysis, or adverse events between mycophenolate mofetil (MMF) and CPA. Remission was reported to improve with MMF however more patients relapsed. A lower dose of steroids was probably as effective as high dose and may be safer, causing fewer infections; kidney function and relapse were not reported. There was little of no difference in death or remission between six and 12 pulses of CPA. There is low certainty evidence that there were less relapses with 12 pulses (2 studies: RR 1.57, 95% CI 0.96 to 2.56; I = 0%), but more infections (2 studies: RR 0.79, 95% CI 0.36 to 1.72; I = 45%). One study reported severe adverse events were less in patients receiving six compared to 12 pulses of CPA. Kidney function and dialysis were not reported. There is limited evidence from single studies about the effectiveness of intravenous immunoglobulin, avacopan, methotrexate, immunoadsorption, lymphocytapheresis, or etanercept. Maintenance therapy: Azathioprine (AZA) has equivalent efficacy as a maintenance agent to CPA with fewer episodes of leucopenia. MMF resulted in a higher relapse rate when tested against azathioprine in remission maintenance. Rituximab is an effective remission induction and maintenance agent. Oral co-trimoxazole did not reduce relapses in granulomatosis with polyangiitis. There were fewer relapses but more serious adverse events with leflunomide compared to methotrexate. There is limited evidence from single studies about the effectiveness of methotrexate versus CPA or AZA, cyclosporin versus CPA, extended versus standard AZA, and belimumab.
AUTHORS' CONCLUSIONS
Plasma exchange was effective in patients with severe AKI secondary to vasculitis. Pulse cyclophosphamide may result in an increased risk of relapse when compared to continuous oral use but a reduced total dose. Whilst CPA is standard induction treatment, rituximab and MMF were also effective. AZA, methotrexate and leflunomide were effective as maintenance therapy. Further studies are required to more clearly delineate the appropriate place of newer agents within an evidence-based therapeutic strategy.
Topics: Acute Kidney Injury; Adult; Azathioprine; Cyclophosphamide; Glomerulonephritis; Humans; Immunosuppressive Agents; Kidney; Kidney Diseases; Kidney Failure, Chronic; Plasma Exchange; Randomized Controlled Trials as Topic; Vasculitis
PubMed: 31927782
DOI: 10.1002/14651858.CD003232.pub4 -
Cell Transplantation 2023High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard of care for selected patients with refractory/relapsed Hodgkin's lymphoma... (Meta-Analysis)
Meta-Analysis
BeEAM (Bendamustine, Etoposide, Cytarabine, Melphalan) Versus BEAM (Carmustine, Etoposide, Cytarabine, Melphalan) as Conditioning Regimen Before Autologous Haematopoietic Cell Transplantation: A Systematic Review and Meta-Analysis.
High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard of care for selected patients with refractory/relapsed Hodgkin's lymphoma (HL) or non-Hodgkin's lymphoma (NHL), and it is also used as first-line clinical consolidation option for some aggressive NHL subtypes. Conditioning regimen prior to ASCT is one of the essential factors related with clinical outcomes post transplant. The conditioning regimen of carmustine, etoposide, cytarabine, and melphalan (BEAM) traditionally is considered the standard of care for patients with lymphoma who are eligible for transplantation. Replacement of carmustine with bendamustine (BeEAM) was described as an alternative conditioning regimen in the autograft setting for patients with lymphoma. Several studies have reported inconsistent clinical outcomes comparing BeEAM and BEAM. Therefore, in the lack of well-designed prospective comparative studies, the comparison of BeEAM versus BEAM is based on retrospective trials. To compare the clinical outcomes between BeEAM and BEAM, we performed a meta-analysis of 10 studies which compared the outcomes between BeEAM and BEAM in patients autografted for lymphoma disease (HL or NHL). We searched article titles and compared transplantation with BeEAM versus BEAM in MEDLINE (PubMed), Cochrane library, and EMBASE database. Here, we report the results of nine main endpoints in our meta-analysis comparing BeEAM and BEAM, including neutrophil engraftment (NE), platelet engraftment (PE), overall survival (OS), progression free survival (PFS), non-relapse mortality (NRM), relapse rate (RR), grade 3 mucositis, renal toxicity, and cardiotoxicity. We discovered that the BeEAM regimen was associated with a slightly better PFS [pooled odds ratio (OR) of 0.70, 95% confidence interval (CI), 0.52-0.94, = 0.02], lower RR (0.49, 95% CI, 0.31-0.76, = 0.002), higher mucositis (3.43, 95% CI, 2.29-5.16, = 0.001), renal toxicity (4.49, 95% CI, 2.68-7.51, = 0.001), and cardiotoxicity (1.88, 95% CI, 1.03-3.40, = 0.03). We also discovered that the two groups had equivalent NE (pooled WMD -0.64, 95% CI, -1.46 to 0.18, = 0.13), PE (pooled WMD -0.3, 95% CI, -1.68 to 2.28, = 0.77), OS (0.73, 95% CI, 0.52-1.01, = 0.07), and NRM (1.51, 95% CI, 0.76-2.98, = 0.24). The results of this meta-analysis show that the BeEAM regimen is a viable alternative to BEAM. More prospective comparisons between BeEAM and BEAM are required.
Topics: Humans; Carmustine; Transplantation, Autologous; Bendamustine Hydrochloride; Hematopoietic Stem Cell Transplantation; Cytarabine; Etoposide; Melphalan; Cardiotoxicity; Mucositis; Retrospective Studies; Neoplasm Recurrence, Local; Lymphoma, Non-Hodgkin
PubMed: 37350429
DOI: 10.1177/09636897231179364 -
Transplantation and Cellular Therapy Sep 2021Haploidentical hematopoietic cell transplantation (haplo-HCT) with post-transplantation cyclophosphamide (PTCy) may be the sole available curative option for several... (Meta-Analysis)
Meta-Analysis
Outcomes after Haploidentical Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide: A Systematic Review and Meta-Analysis Comparing Myeloablative with Reduced-Intensity Conditioning Regimens and Bone Marrow with Peripheral Blood Stem Cell Grafts.
Haploidentical hematopoietic cell transplantation (haplo-HCT) with post-transplantation cyclophosphamide (PTCy) may be the sole available curative option for several hematologic malignancies. However, the best choice of conditioning regimen and graft source has not been established. This study was conducted to compare myeloablative conditioning (MAC) regimens with reduced-intensity conditioning (RIC) regimens and peripheral blood stem cell (PBSC) grafts with bone marrow (BM) grafts in the haplo-HCT setting with PTCy. We performed a systematic review and meta-analysis of studies comparing MAC with RIC and PBSC with BM in the haplo-HCT. The search was conducted in PubMed and TRIALS on February 2, 2021, without a date limit. We excluded studies with >30% non-PTCy graft-versus-host disease (GVHD) prophylaxis and >30% nonmalignant diseases. We screened 570 abstracts from PubMed and TRIALS and selected 20 for full-text review and 17 for inclusion in the qualitative and quantitative analyses. For PBSC versus BM grafts, we found no difference in overall survival (OS; hazard ratio [HR], 1.05; P = .61; nPBSC = 1983; nBM = 2124), progression-free survival (PFS; HR, 0.95; P = .52; nPBSC = 2663, nBM = 2769), graft-versus-host disease (GVHD)-free relapse-free survival (GRFS; HR, 1.16; P = .07; nPBSC = 1454; pBM = 1647), or nonrelapse mortality (HR, 1.14; P = .13; nPBSC = 1664; nBM = 1862). Relapse was lower with the use of PBSC grafts (HR, 0.84; P = .001; nPBSC = 2663; nBM = 2769). The rates of acute GVHD (aGVHD) and chronic GVHD (cGVHD) were higher with PBSC grafts (aGVHD grade II-IV: HR, 1.67; P < .001; nPBSC = 2663; nBM = 2802; aGVHD grade III-IV: HR, 1.82; P < .001; nPBSC = 1826; nBM = 2000; cGVHD: HR, 1.46; P = .002; nPBSC = 2686; nBM = 2815). Engraftment was higher with PBSC grafts (HR, 1.27; P < .001; nPBSC = 1461; nBM = 1717). Comparing MAC and RIC, the use of MAC was associated with less relapse (HR, 0.70; P < .001; nMAC = 1929; nRIC = 2662), higher nonrelapse mortality (HR, 1.24; P = .002; nMAC = 2016; nRIC = 2790), but better PFS (HR, 0.86; P = .002; nMAC = 1929; nRIC = 2662). There were no differences between the 2 conditioning regimens in OS (HR, .95; P = .32; nMAC = 2123; nRIC = 3155), GRFS (HR, 0.97; P = .67; nMAC = 1182; nRIC = 1330), grade II-IV aGVHD (HR, 1.01; P = .81; nMAC = 2099; nRIC = 3090), or cGVHD (HR, 1.05; P = .44; nMAC=1929; nRIC = 2662). This analysis shows that the use of BM grafts is associated with comparable outcomes as seen with PBSC grafts despite a lower incidence of GVHD and a higher relapse rate. The use of MAC regimens is associated with improved PFS. These results suggest that for fit patients, MAC remains the optimal conditioning regimen in terms of mortality, and that the use of PBSC grafts may further decrease relapse risk and hasten engraftment, provided that further strategies can be incorporated to decrease GVHD. Prospective comparisons are awaited.
Topics: Bone Marrow; Cyclophosphamide; Hematopoietic Stem Cell Transplantation; Humans; Neoplasm Recurrence, Local; Peripheral Blood Stem Cells; Prospective Studies
PubMed: 34146733
DOI: 10.1016/j.jtct.2021.06.011 -
BMC Nephrology Feb 2022Hypocomplementemic urticarial vasculitis (HUV) is a rare systemic vasculitis. We aimed to describe the kidney involvement of HUV in a multicenter national cohort with an...
BACKGROUND
Hypocomplementemic urticarial vasculitis (HUV) is a rare systemic vasculitis. We aimed to describe the kidney involvement of HUV in a multicenter national cohort with an extended follow-up.
METHODS
All patients with HUV (international Schwartz criteria) with a biopsy-proven kidney involvement, identified through a survey of the French Vasculitis Study Group (FVSG), were included. A systematic literature review on kidney involvement of HUV was performed.
RESULTS
Twelve patients were included, among whom 8 had positive anti-C1q antibodies. All presented with proteinuria, from mild to nephrotic, and 8 displayed acute kidney injury (AKI), requiring temporary haemodialysis in 2. Kidney biopsy showed membrano-proliferative glomerulonephritis (MPGN) in 8 patients, pauci-immune crescentic GN or necrotizing vasculitis in 3 patients (with a mild to severe interstitial inflammation), and an isolated interstitial nephritis in 1 patient. C1q deposits were observed in the glomeruli (n = 6), tubules (n = 4) or renal arterioles (n = 3) of 8 patients. All patients received corticosteroids, and 9 were also treated with immunosuppressants or apheresis. After a mean follow-up of 8.9 years, 6 patients had a preserved renal function, but 2 patients had developed stage 3-4 chronic kidney disease (CKD) and 4 patients had reached end-stage kidney disease (ESKD), among whom 1 had received a kidney transplant.
CONCLUSION
Renal involvement of HUV can be responsible for severe AKI, CKD and ESRD. It is not always associated with circulating anti-C1q antibodies. Kidney biopsy shows mostly MPGN or crescentic GN, with frequent C1q deposits in the glomeruli, tubules or arterioles.
Topics: Adrenal Cortex Hormones; Adult; Aged; Biopsy; Blood Component Removal; Child; Child, Preschool; Complement C1q; Cyclophosphamide; Female; Follow-Up Studies; Glomerulonephritis, Membranoproliferative; Humans; Immunosuppressive Agents; Male; Middle Aged; Retrospective Studies; Rituximab; Syndrome; Urticaria; Vasculitis
PubMed: 35172758
DOI: 10.1186/s12882-022-02689-8 -
Oxidative Medicine and Cellular... 2022Chagas disease is an anthropozoonosis caused by the protozoan and is characterized as a neglected disease. It is currently endemic in 21 countries on the Latin American... (Review)
Review
Chagas disease is an anthropozoonosis caused by the protozoan and is characterized as a neglected disease. It is currently endemic in 21 countries on the Latin American continent, including Bolivia, Argentina, and Paraguay. Unfortunately, there are no optimally effective treatments that can reduce the damage caused in the digestive form of the disease, such as the neuronal destruction of the myenteric plexus of both the esophagus and the colon. Therefore, the objective of this systematic review was to report the possible pharmacological neuroprotective agents that were tested in murine models of the digestive form of Chagas disease. Inclusion criteria are experimental studies that used different murine models for digestive forms of Chagas disease related to pharmacological interventions with neuroprotective potential, without year and language restriction. On the other hand, the exclusion criteria were studies that did not approach murine models with the digestive form of the disease or did not use neuroprotective treatments, among others. The search in the PubMed, Web of Science, Embase, and LILACS databases was performed on September 4, 2021. In addition, a manual search was performed using the references of the included articles. The risk of bias assessment of the studies was performed based on the SYRCLE tool guidelines, and the data from the selected articles are presented in this review as a narrative description and in tables. Eight articles were included, 4 of which addressed treatment with acetylsalicylic acid, 3 with cyclophosphamide, and 1 with Lycopodium clavatum 13c. In view of the results of the studies, most of them show neuroprotective activity of the treatments, with the potential to reduce the number of damaged neurons, as well as positive changes in the structure of these cells. However, more studies are needed to understand the mechanisms triggered by each drug, as well as their safety and immunogenicity. Systematic review registration is as follows: PROSPERO database (CRD42022289746).
Topics: Animals; Aspirin; Chagas Disease; Cyclophosphamide; Humans; Mice; Neuroprotective Agents; Trypanosoma cruzi
PubMed: 36199427
DOI: 10.1155/2022/9397290 -
The Cochrane Database of Systematic... Jun 2021This an update of a Cochrane Review. Paraquat is a widely used herbicide, but is also a lethal poison. In some low- and middle-income countries (LMICs) paraquat is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This an update of a Cochrane Review. Paraquat is a widely used herbicide, but is also a lethal poison. In some low- and middle-income countries (LMICs) paraquat is commonly available and inexpensive, making poisoning prevention difficult. Most of the people poisoned by paraquat have taken it as a means of self-poisoning. Standard treatment for paraquat poisoning prevents further absorption and reduces the load of paraquat in the blood through haemoperfusion or haemodialysis. The effectiveness of standard treatments is extremely limited. The immune system plays an important role in exacerbating paraquat-induced lung fibrosis. Immunosuppressive treatment using glucocorticoid and cyclophosphamide in combination has been developed and studied as an intervention for paraquat poisoning.
OBJECTIVES
To assess the effects of glucocorticoid with cyclophosphamide for moderate to severe oral paraquat poisoning.
SEARCH METHODS
The most recent searches were run in September 2020. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Injuries Trials Register), Ovid MEDLINE(R), Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid OLDMEDLINE, Embase Classic + Embase (Ovid), ISI WOS (SCI-EXPANDED, SSCI, CPCI-S, and CPSI-SSH), and trials registries. We also searched the following three resources: China National Knowledge Infrastructure database (CNKI ); Wanfang Data (); and VIP () on 12 November 2020. We examined the reference lists of included studies and review papers.
SELECTION CRITERIA
We included randomised controlled trials (RCTs). For this update, in accordance with Cochrane Injuries' Group policy (2015), we included only prospectively registered RCTs for trials published after 2010. We included trials which assessed the effects of glucocorticoid with cyclophosphamide delivered in combination. Eligible comparators were standard care (with or without a placebo), or any other therapy in addition to standard care. Outcomes of interest included mortality and infections.
DATA COLLECTION AND ANALYSIS
We calculated the mortality risk ratio (RR) and 95% confidence interval (CI). Where possible, we summarised data for all-cause mortality at relevant time periods (from hospital discharge to three months after discharge) in meta-analysis, using a fixed-effect model. We conducted sensitivity analyses based on factors including whether participants were assessed at baseline for plasma paraquat levels. We also reported data on infections within one week after initiation of treatment.
MAIN RESULTS
We included four trials with a total of 463 participants. The included studies were conducted in Taiwan (Republic of China), Iran, and Sri Lanka. Most participants were male. The mean age of participants was 28 years. We judged two of the four included studies, including the largest and most recently conducted study (n = 299), to be at low risk of bias for key domains including sequence generation. We assessed one study to be at high risk of selection bias and another at unclear risk, since allocation concealment was either not mentioned in the trial report or explicitly not undertaken. We assessed three of the four studies to be at unclear risk of selective reporting, as no protocols could be identified. An important source of heterogeneity amongst the included studies was the method of assessment of participants' baseline severity using analysis of plasma levels (two studies employed this method, whilst the other two did not). No studies assessed the outcome of mortality at 30 days following ingestion of paraquat. Low-certainty evidence from two studies indicates that glucocorticoids with cyclophosphamide in addition to standard care may slightly reduce the risk of death in hospital compared to standard care alone ((RR 0.82, 95% CI 0.68 to 0.99; participants = 322); results come from sensitivity analysis excluding studies not assessing plasma at baseline). However, we have limited confidence in this finding as heterogeneity was high (I = 77%) and studies varied in terms of size and comparators. A single large study provided data showing that there may be little or no effect of treatment at three months post discharge from hospital (RR 0.98, 95% CI 0.85 to 1.13; 1 study, 293 participants; low-certainty evidence); however, analysis of long-term results amongst participants whose injuries arose from self-poisoning must be interpreted with caution. We remain uncertain of the effect of glucocorticoids with cyclophosphamide on infection within one week after initiation of the treatment; this outcome was assessed by two small studies only (31 participants, very low-certainty evidence) that considered leukopenia as a proxy or risk factor for infection. Neither study reported infections in any participants.
AUTHORS' CONCLUSIONS
Low-certainly evidence suggests that glucocorticoids with cyclophosphamide in addition to standard care may slightly reduce mortality in hospitalised people with oral paraquat poisoning. However, we have limited confidence in this finding because of substantial heterogeneity and concerns about imprecision. Glucocorticoids with cyclophosphamide in addition to standard care may have little or no effect on mortality at three months after hospital discharge. We are uncertain whether glucocorticoid with cyclophosphamide puts patients at an increased risk of infection due to the limited evidence available for this outcome. Future research should be prospectively registered and CONSORT-compliant. Investigators should attempt to ensure an adequate sample size, screen participants for inclusion rigorously, and seek long-term follow-up of participants. Investigators may wish to research the effects of glucocorticoid in combination with other treatments.
Topics: Adult; Bias; Cause of Death; Cyclophosphamide; Drug Therapy, Combination; Female; Glucocorticoids; Herbicides; Humans; Immunosuppressive Agents; Male; Paraquat; Poisoning; Pulmonary Fibrosis; Randomized Controlled Trials as Topic; Time Factors
PubMed: 34190331
DOI: 10.1002/14651858.CD008084.pub5 -
Medicine Apr 2020Rituximab (RTX) is considered to be a promising drug for curing membranous nephropathy. However, the efficacy and safety of RTX in treating membranous nephropathy remain... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND AND OBJECTIVES
Rituximab (RTX) is considered to be a promising drug for curing membranous nephropathy. However, the efficacy and safety of RTX in treating membranous nephropathy remain uncertain. This meta-analysis aimed to investigate the efficacy and safety of RTX in patients with membranous nephropathy.
METHODS
A literature search was performed using Pubmed, Embase, OVID, and Cochrane Library and randomized controlled trials (RCTs) case-controls and cohort studies published till 30 July 2019 were assessed. The studies assessing the efficacy and safety of RTX in patients with membranous nephropathy were included.
RESULTS
Eight relevant trials involving 542 patients were included in the meta-analysis. It was found that RTX did not significantly improve serum albumin levels and e-GFR when compared with the control group (including cyclosporine and cyclophosphamide, chlorambucil, prednisone, non-immunosuppressive anti-proteinuria treatment), serum albumin levels (OR = 0.31, 95%CI-0.12-0.74, P = .15), e-GFR (OR = -1.49, 95%CI-17.14-14.17, P = .85). However, RTX did reduce the serum creatinine (OR = -0.01, 95%CI-0.36-0.34, P = .95) and urinary protein (OR = -2.39, 95%CI -7.30 -2.53, P = .34) levels. Also, in comparison to the control group, RTX did improve the total remission rate (OR = 1.63, 95%CI 0.48-5.54, P = .43), achieve a higher rate of complete remission (OR = 2.54, 95%CI 1.65-3.90, P < .01) and also reduced the amount of M-type phospholipase A2 receptor-Antibody depletion in patients (OR = 5.59, 95%CI 1.81-17.2, P = .003). RTX-related adverse events were mostly mild (most infusion-related reactions) in nature and serious adverse events were rare.
CONCLUSION
RTX proved to be efficient, well-tolerated and a safe drug in the treatment of membranous nephropathy. Most patients reach complete remission during the follow-up period, and relapse is rare. RTX may turn out to be promising in membranous nephropathy patients.
Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Case-Control Studies; Chlorambucil; Cyclophosphamide; Cyclosporine; Female; Glomerular Filtration Rate; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Male; Middle Aged; Prednisone; Proteinuria; Randomized Controlled Trials as Topic; Receptors, Phospholipase A2; Remission Induction; Rituximab; Safety; Serum Albumin; Treatment Outcome
PubMed: 32311997
DOI: 10.1097/MD.0000000000019804 -
Medicine Oct 2018The clinical benefits provided by using anthracycline-contained regimens in patients with early breast cancer (EBC) remain uncertain. This meta-analysis used data from... (Comparative Study)
Comparative Study Meta-Analysis Review
PURPOSE
The clinical benefits provided by using anthracycline-contained regimens in patients with early breast cancer (EBC) remain uncertain. This meta-analysis used data from all relevant trials to compare treatment outcomes for patients with EBC receiving adjuvant chemotherapy with non-anthracycline-contained regimens or anthracycline-contained regimens.
PATIENTS AND METHODS
Individual patient data were collected on 7 randomized trials comparing non-anthracycline-contained regimens with anthracycline-contained regimens, a total of 14,451 women were analyzed. The hazard ratios (HR) of disease-free survival (DFS) and overall survival (OS), and the risk ratios for grades 3 to 4 toxicities were extracted from the retrieved studies and analyzed using various statistical methods. A pooled analysis was accomplished and HR with 95% confidence intervals (95% CIs) was derived. The significant differences in DFS and OS were explored. A heterogeneity test was applied as well.
RESULTS
Among 7 eligible trials, significant differences in favor of anthracycline-contained regimens were seen in DFS (HR: 0.86; 95% CI: 0.78-0.95; P = .003) and in OS (HR: 0.85; 95% CI: 0.75-0.97; P = .01). Subgroup analyses of DFS showed similar treatment effects by hormone-receptor status and nodal status, but differential effects by human epidermal growth factor receptor 2 status, menopausal status, and malignancy grade. Sensitive analysis showed that the DFS of taxanes and cyclophosphamide (TC) was noninferior to anthracycline-contained regiments.
CONCLUSION
Despite failing to show noninferior to the anthracycline-contained regimens in patients with EBC, it provides evidence that both regimens significantly improved the DFS and OS, and TC regimen may be noninferior to anthracycline-contained regimens.
Topics: Adolescent; Adult; Aged; Anthracyclines; Antineoplastic Agents; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Disease-Free Survival; Female; Humans; Middle Aged; Taxoids; Treatment Outcome; Young Adult
PubMed: 30335021
DOI: 10.1097/MD.0000000000012908 -
The Cochrane Database of Systematic... Oct 2016The majority of children who present with their first episode of nephrotic syndrome achieve remission with corticosteroid therapy. Children who fail to respond may be... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The majority of children who present with their first episode of nephrotic syndrome achieve remission with corticosteroid therapy. Children who fail to respond may be treated with immunosuppressive agents including calcineurin inhibitors (cyclosporin or tacrolimus) and with non-immunosuppressive agents such as angiotensin-converting enzyme inhibitors (ACEi). Optimal combinations of these agents with the least toxicity remain to be determined. This is an update of a review first published in 2004 and updated in 2006 and 2010.
OBJECTIVES
To evaluate the benefits and harms of different interventions used in children with idiopathic nephrotic syndrome, who do not achieve remission following four weeks or more of daily corticosteroid therapy.
SEARCH METHODS
We searched Cochrane Kidney and Transplant's Specialised Register (up to 2 March 2016) through contact with the Information Specialist using search terms relevant to this review.
SELECTION CRITERIA
RCTs and quasi-RCTs were included if they compared different immunosuppressive agents or non-immunosuppressive agents with placebo, prednisone or other agent given orally or parenterally in children aged three months to 18 years with SRNS.
DATA COLLECTION AND ANALYSIS
Two authors independently searched the literature, determined study eligibility, assessed risk of bias and extracted data. For dichotomous outcomes, results were expressed as risk ratios (RR) and 95% confidence intervals (CI). Data were pooled using the random effects model.
MAIN RESULTS
Nineteen RCTs (820 children enrolled; 773 evaluated) were included. Most studies were small. Eleven studies were at low risk of bias for allocation concealment and only four studies were at low risk of performance bias. Fifteen, eight and 10 studies were at low risk of detection bias, attrition bias and reporting bias respectively. Cyclosporin when compared with placebo or no treatment significantly increased the number of children who achieved complete remission. However this was based on only eight children who achieved remission with cyclosporin compared with no children who achieved remission with placebo/no treatment in three small studies (49 children: RR 7.66, 95% CI 1.06 to 55.34). Calcineurin inhibitors significantly increased the number with complete or partial remission compared with IV cyclophosphamide (2 studies, 156 children: RR 1.98, 95% CI 1.25 to 3.13; I = 20%). There was no significant differences in the number who achieved complete remission between tacrolimus versus cyclosporin (1 study, 41 children: RR 0.86, 95% CI 0.44 to 1.66), cyclosporin versus mycophenolate mofetil plus dexamethasone (1 study, 138 children: RR 2.14, 95% CI 0.87 to 5.24), oral cyclophosphamide with prednisone versus prednisone alone (2 studies, 91 children: RR 1.06, 95% CI 0.61 to 1.87), IV versus oral cyclophosphamide (1 study, 11 children: RR 3.13, 95% CI 0.81 to 12.06), IV cyclophosphamide versus oral cyclophosphamide plus IV dexamethasone (1 study, 49 children: RR 1.13, 95% CI 0.65 to 1.96), and azathioprine with prednisone versus prednisone alone (1 study, 31 children: RR 0.94, 95% CI 0.15 to 5.84). One study found no significant differences between three agents (cyclophosphamide, mycophenolate mofetil, leflunomide) used in combination with tacrolimus and prednisone. One study found no significant difference in the percentage reduction in proteinuria (31 children: -12; 95% CI -73 to 110) between rituximab with cyclosporin/prednisolone and cyclosporin/prednisolone alone. Two studies reported ACEi significantly reduced proteinuria.
AUTHORS' CONCLUSIONS
To date RCTs have demonstrated that calcineurin inhibitors increase the likelihood of complete or partial remission compared with placebo/no treatment or cyclophosphamide. For other regimens assessed, it remains uncertain whether the interventions alter outcomes because the certainty of the evidence is low. Further adequately powered, well designed RCTs are needed to evaluate other regimens for children with idiopathic SRNS. Since SRNS represents a spectrum of diseases, future studies should enrol children from better defined groups of patients with SRNS.
Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Azathioprine; Child; Child, Preschool; Cyclophosphamide; Cyclosporine; Dexamethasone; Drug Resistance; Glucocorticoids; Humans; Immunosuppressive Agents; Infant; Isoxazoles; Leflunomide; Mycophenolic Acid; Nephrotic Syndrome; Prednisone; Randomized Controlled Trials as Topic; Remission Induction
PubMed: 27726125
DOI: 10.1002/14651858.CD003594.pub5 -
Journal of Healthcare Engineering 2022To observe the therapeutic effect and the incidence of adverse reactions of total body irradiation plus cyclophosphamide (TBI/CY) and busulfan plus cyclophosphamide... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To observe the therapeutic effect and the incidence of adverse reactions of total body irradiation plus cyclophosphamide (TBI/CY) and busulfan plus cyclophosphamide (BU/CY) in the treatment of pediatric hematopoietic stem cell transplantation.
METHODS
By searching the Cochrane Library, PubMed, Web of Knowledge, Embase, Chinese Biomedical Literature Database (CBM), and screening randomized controlled trials (RCTs), quality evaluation and data extraction were performed for the included literature, and meta-analysis was performed for RCTs included at using Review Manager 5.2 software.
RESULTS
A total of 10160 patients were enrolled in 15 RCTs, including 5211 patients in the TBI/CY group and 4949 patients in the BU/CY group. Meta-analysis showed that there was a statistical difference in transplant failure rate (OR = 1.56, 95% CI (1.23, 1.97), = 0.0002, = 56%, = 3.69), transplant mortality (OR = 1.45, 95% CI (1.24, 1.68), < 0.00001, = 76%, = 4.80), transplantation long-term disease-free survival rate (OR = 1.52, 95% CI (1.09, 2.12), = 0.01, = 0%, = 2.50), and transplantation adverse reactions (OR = 1.28, 95% CI (1.08, 1.52), = 0.004, = 0%, = 2.85).
CONCLUSION
Meta-analysis showed that TBI/CY combined pretreatment regimen was more effective than BU/CY regimen alone in the treatment of pediatric hematologic transplantation, with a lower incidence of adverse reactions and significant long-term survival efficacy.
Topics: Busulfan; Child; Cyclophosphamide; Humans; Leukemia; Transplantation Conditioning; Treatment Outcome
PubMed: 35340233
DOI: 10.1155/2022/2825712