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Annals of Hematology Feb 2021Autologous stem cell transplantation as a frontline treatment for patients with multiple myeloma (MM) requires an adequate peripheral blood stem cell (PBSC) collection... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of the efficiency, safety, and survival outcomes in two stem cell mobilization regimens with cyclophosphamide plus G-CSF or G-CSF alone in multiple myeloma: a meta-analysis.
Autologous stem cell transplantation as a frontline treatment for patients with multiple myeloma (MM) requires an adequate peripheral blood stem cell (PBSC) collection before processing. Granulocyte-colony stimulating factor (G-CSF) with or without cyclophosphamide (CTX) is a common regimen for PBSC mobilization; their benefits and risks are controversial. To compare the efficiency, safety, and survival outcomes between the two regimens, we conducted a meta-analysis including 18 studies with 4 prospective and 14 retrospective studies; a total of 2770 patients with MM were analyzed. The CTX plus G-CSF regimen had higher yields of total CD34 cells (SMD = 0.39, 95% CI (0.30, 0.49)), and higher mobilization rates of the target ⩾ 2 × 10/kg (OR = 3.34, 95% CI (1.82, 6.11)) and 4 × 10/kg (OR = 2.16, 95% CI (1.69, 2.76)) cells. A favorable event-free survival (EFS) (HR = 0.73, 95% CI (0.58, 0.93), p = 0.01) and better 3-year EFS rate (OR = 1.65, 95% CI (1.1, 2.47), p = 0.02) were also reached in the patients with CTX plus G-CSF mobilization, although the risks of admission (OR = 26.49, 95% CI (7.31, 95.97)) and fever (OR = 13.66, 95% CI (6.21, 30.03)) during mobilization were increased, the treatment-related mortality was consistent (p = 0.26). The CTX plus G-CSF regimen was superior to the G-CSF-alone regimen for PBSC mobilization in patients with MM.
Topics: Autografts; Cyclophosphamide; Disease-Free Survival; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Multiple Myeloma; Safety; Survival Rate
PubMed: 33404694
DOI: 10.1007/s00277-020-04376-w -
Medicine Sep 2020Lupus nephritis (LN) remains a predominant cause of morbidity and mortality in SLE. Here we performed a meta-analysis to evaluate the efficacy and safety of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lupus nephritis (LN) remains a predominant cause of morbidity and mortality in SLE. Here we performed a meta-analysis to evaluate the efficacy and safety of the induction treatment with mycophenolate mofetil (MMF) and cyclophosphamide (CYC) for LN.
METHODS
Relevant literature was searched by computer from the establishment of the database to November 2019. A meta-analysis was conducted to analysis the efficacy and safety between mycophenolate mofetil and cyclophosphamide as induction therapy in LN patients. The primary end-point was response to urine protein, serum creatinine (Scr) and serum complement C3, and the secondary end-points were complete remission and adverse reactions.
RESULTS
Eighteen articles were selected for the final meta-analysis, involving 1989 patients with LN, of which the renal biopsy result could be classified into class III-V according to the standards of WHO/ISN. The results revealed that MMF was superior to CYC in increasing the level of serum complement C3 [SMD = 0.475, 95%CI (0.230-0.719)] and complete remission [RR = 1.231, 95%CI (1.055-1.437)]. Furthermore, the subgroup analysis showed that it was in Asian patients, rather than in Caucasian patients, that CYC exerted a better effect on lowering the level of urine protein (UPRO) than MMF [SMD = 0.405, 95%CI (0.081-0.730)]. Besides, when the initial UPRO level was less than 4 g/day, the effect of CYC was better than MMF [SMD = 0.303, 95%CI (0.014-0.591)]. There was no significant difference between MMF and CYC in improving Scr [SMD = 0.090, 95%CI (-0.060-0.239)]. When it came to the comparison of safety between MMF and CYC, the meta-analysis showed that MMF was superior to CYC in decreasing infection in Caucasian patients [RR = 0.727, 95%CI (0.532-0.993)], reducing the risk of leukopenia and menstrual abnormalities in Asian patients and lowering the frequency of gastrointestinal symptoms [RR = 0.639, 95%CI (0.564-0.724)], independent of race.
CONCLUSIONS
MMF precedes CYC in improving serum complement C3 and complete remission regardless of race, as well as shows fewer adverse drug reactions in the induction treatment of LN belonging to type III-V. But for Asian patients or those initial UPRO levels are less than 4 g/day, CYC may be superior to MMF.
Topics: Adult; Cyclophosphamide; Female; Humans; Lupus Nephritis; Male; Mycophenolic Acid; Randomized Controlled Trials as Topic; Remission Induction
PubMed: 32957400
DOI: 10.1097/MD.0000000000022328 -
Clinical & Translational Oncology :... Jun 2021Considering the increased cancer patient survivorship, the focus is now on addressing the impacts of treatment on quality of life. In young people, altered reproductive...
PURPOSE
Considering the increased cancer patient survivorship, the focus is now on addressing the impacts of treatment on quality of life. In young people, altered reproductive function is a major issue and its effects in young males are largely neglected by novel research. To improve clinician awareness, we systematically reviewed side effects of chemotherapy for Hodgkin lymphoma (HL) in young males.
METHODS
The review was prospectively registered (PROSPERO N. CRD42019122868). Three databases (Medline via PUBMED, SCOPUS, and Cochrane Library) were searched for studies featuring males aged 13-51-years who underwent chemotherapy for HL using ABVD (Adriamycin® (doxorubicin), bleomycin, vinblastine, and dacarbazine) or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) regimens. These chemotherapy regimens were compared against each other using sperm characteristics, FSH, and inhibin B levels to measure fertility levels.
RESULTS
Data were extracted from five studies featuring 1344 patients. 6 months post-ABVD saw marked deterioration in sperm count, further reduced by more cycles (P = 0.05). Patients treated with BEACOPP rather than ABVD were more prone to oligospermia. Receiving fewer cycles of both regimens increased the likelihood of sperm production recovering. Patients treated with 6-8 cycles of BEACOPP did not recover spermiogenesis.
CONCLUSIONS
ABVD and BEACOPP regimens significantly reduce fertility function to varying effects depending on treatment duration. ABVD temporarily causes significant reductions in male fertility, whereas BEACOPP's effects are more permanent. Therefore, clinicians should discuss fertility preservation with male patients receiving infertility-inducing gonadotoxic therapy. Further high-quality studies are required to more adequality describe the risk to fertility by chemotherapy.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Fertility; Hodgkin Disease; Humans; Infertility, Male; Male; Prednisone; Procarbazine; Vinblastine; Vincristine
PubMed: 32944834
DOI: 10.1007/s12094-020-02483-8 -
Medicine Aug 2020Mycophenolate mofetil (MMF) has been recommended for the treatment of lupus nephritis (LN). Although inter-racial differences exist regarding the appropriate dose and... (Meta-Analysis)
Meta-Analysis
BACKGROUD
Mycophenolate mofetil (MMF) has been recommended for the treatment of lupus nephritis (LN). Although inter-racial differences exist regarding the appropriate dose and efficacy of MMF in patients with LN, no definitive meta-analysis has yet been conducted in Chinese patients. This analysis investigated the efficacy and safety of MMF in Chinese patients with proliferative LN.
METHODS
A systematic literature search was conducted to select randomized controlled trials that reported at least one of the following: complete remission (CR), partial remission, total remission (TR; defined as complete remission + partial remission), relapse rate, serum creatinine, creatinine clearance, end-stage renal disease, death, infections, amenorrhea, leukopenia, alopecia, gastrointestinal symptoms, or liver damage.
RESULTS
Eighteen trials (927 patients) were included; 14 (750 patients) reported CR, partial remission, and TR. Two trials (58 patients) reported relapse rates during maintenance treatment. MMF induction significantly improved CR and TR vs cyclophosphamide (relative risk 1.34, 95% confidence interval: 1.13-1.58; P < .001; relative risk 1.16, 95% confidence interval: 1.02-1.33; P = .03), and was associated with significantly lower risks of infection (P < .001), amenorrhea (P < .001), leukopenia, and alopecia. No significant difference in relapse rate was evident between the MMF and azathioprine groups (P = .66).
CONCLUSION
According to this meta-analysis of 18 trials, MMF is significantly more effective than cyclophosphamide induction, and is associated with reduced incidences of infections, amenorrhea, leukopenia, and alopecia in Chinese patients with proliferative LN.
Topics: Asian People; China; Cyclophosphamide; Enzyme Inhibitors; Humans; Immunosuppressive Agents; Lupus Nephritis; Mycophenolic Acid; Randomized Controlled Trials as Topic
PubMed: 32871981
DOI: 10.1097/MD.0000000000021121 -
RMD Open Apr 2020A few studies on antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treatments have shown the therapeutic efficacy of mycophenolate mofetil (MMF).... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVES
A few studies on antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treatments have shown the therapeutic efficacy of mycophenolate mofetil (MMF). However, the therapeutic efficacy of MMF compared with that of cyclophosphamide (CYC) in patients with AAV has not been established. We conducted a systematic review and meta-analysis to assess the efficacy of MMF as a remission induction therapy in patients with AAV comparing it with the efficacy of CYC.
METHODS
We searched randomised controlled trials (RCTs) comparing the efficacy of MMF with that of CYC in patients with AAV on three different websites: PubMed, Cochrane Library and Google Scholar. We compared the difference in the relative risk (RR) of each outcome based on a Mantel-Haenszel random-effects model.
RESULTS
We analysed data from four RCTs with 300 patients for the study. The 6-month remission rate (RR 1.09, 95% CI 0.86 to 1.38, p=0.48), the 6-month ANCA negativity (RR 1.31, 95% CI 0.91 to 1.90, p=0.15) and the long-term relapse rate (RR 1.36, 95% CI 0.80 to 2.31, p=0.26) were all similar between the two treatments. The rates of death, infection and leucopenia were also similar between the two groups (RR 1.05, 95% CI 0.40 to 2.74, p=0.93; RR 1.26, 95% CI 0.79 to 2.01, p=0.33; RR 0.45, 95% CI 0.16 to 1.32, p=0.15, respectively).
CONCLUSIONS
We found no difference between the therapeutic efficacy of MMF and that of CYC in patients with AAV. MMF may be an alternative remission induction therapy in patients with non-life-threatening AAV.
Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Cyclophosphamide; Humans; Immunosuppressive Agents; Leukopenia; Mycophenolic Acid; Randomized Controlled Trials as Topic; Recurrence; Remission Induction; Treatment Outcome
PubMed: 32371435
DOI: 10.1136/rmdopen-2020-001195 -
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 -
The Cochrane Database of Systematic... Apr 2020About 80% of children with steroid-sensitive nephrotic syndrome (SSNS) have relapses. Of these children, half relapse frequently, and are at risk of adverse effects from... (Meta-Analysis)
Meta-Analysis
BACKGROUND
About 80% of children with steroid-sensitive nephrotic syndrome (SSNS) have relapses. Of these children, half relapse frequently, and are at risk of adverse effects from corticosteroids. While non-corticosteroid immunosuppressive medications prolong periods of remission, they have significant potential adverse effects. Currently, there is no consensus about the most appropriate second-line agent in children who are steroid sensitive, but who continue to relapse. In addition, these medications could be used with corticosteroids in the initial episode of SSNS to prolong the period of remission. This is the fourth update of a review first published in 2001 and updated in 2005, 2008 and 2013.
OBJECTIVES
To evaluate the benefits and harms of non-corticosteroid immunosuppressive medications in SSNS in children with a relapsing course of SSNS and in children with their first episode of nephrotic syndrome.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 10 March 2020 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 (RCTs) or quasi-RCTs were included if they involved children with SSNS and compared non-corticosteroid immunosuppressive medications with placebo, corticosteroids (prednisone or prednisolone) or no treatment; compared different non-corticosteroid immunosuppressive medications or different doses, durations or routes of administration of the same non-corticosteroid immunosuppressive medication.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed study eligibility, risk of bias of the included studies and extracted data. Statistical analyses were performed using a random-effects model and results expressed as risk ratio (RR) for dichotomous outcomes or mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). The certainty of the evidence was assessed using GRADE.
MAIN RESULTS
We identified 43 studies (91 reports) and included data from 2428 children. Risk of bias assessment indicated that 21 and 24 studies were at low risk of bias for sequence generation and allocation concealment respectively. Nine studies were at low risk of performance bias and 10 were at low risk of detection bias. Thirty-seven and 27 studies were at low risk of incomplete and selective reporting respectively. Rituximab (in combination with calcineurin inhibitors (CNI) and prednisolone) versus CNI and prednisolone probably reduces the number of children who relapse at six months (5 studies, 269 children: RR 0.23, 95% CI 0.12 to 0.43) and 12 months (3 studies, 198 children: RR 0.63, 95% CI 0.42 to 0.93) (moderate certainty evidence). At six months, rituximab resulted in 126 children/1000 relapsing compared with 548 children/1000 treated with conservative treatments. Rituximab may result in infusion reactions (4 studies, 252 children: RR 5.83, 95% CI 1.34 to 25.29). Mycophenolate mofetil (MMF) and levamisole may have similar effects on the number of children who relapse at 12 months (1 study, 149 children: RR 0.90, 95% CI 0.70 to 1.16). MMF may have a similar effect on the number of children relapsing compared to cyclosporin (2 studies, 82 children: RR 1.90, 95% CI 0.66 to 5.46) (low certainty evidence). MMF compared to cyclosporin is probably less likely to result in hypertrichosis (3 studies, 140 children: RR 0.23, 95% CI 0.10 to 0.50) and gum hypertrophy (3 studies, 144 children: RR 0.09, 95% CI 0.07 to 0.42) (low certainty evidence). Levamisole compared with steroids or placebo may reduce the number of children with relapse during treatment (8 studies, 474 children: RR 0.52, 95% CI 0.33 to 0.82) (low certainty evidence). Levamisole compared to cyclophosphamide may make little or no difference to the risk for relapse after 6 to 9 months (2 studies, 97 children: RR 1.17, 95% CI 0.76 to 1.81) (low certainty evidence). Cyclosporin compared with prednisolone may reduce the number of children who relapse (1 study, 104 children: RR 0.33, 95% CI 0.13 to 0.83) (low certainty evidence). Alkylating agents compared with cyclosporin may make little or no difference to the risk of relapse during cyclosporin treatment (2 studies, 95 children: RR 0.91, 95% CI 0.55 to 1.48) (low certainty evidence) but may reduce the risk of relapse at 12 to 24 months (2 studies, 95 children: RR 0.51, 95% CI 0.35 to 0.74), suggesting that the benefit of the alkylating agents may be sustained beyond the on-treatment period (low certainty evidence). Alkylating agents (cyclophosphamide and chlorambucil) compared with prednisone probably reduce the number of children, who experience relapse at six to 12 months (6 studies, 202 children: RR 0.44, 95% CI 0.32 to 0.60) and at 12 to 24 months (4 studies, 59 children: RR 0.20, 95% CI 0.09 to 0.46) (moderate certainty evidence). IV cyclophosphamide may reduce the number of children with relapse compared with oral cyclophosphamide at 6 months (2 studies, 83 children: RR 0.54, 95% CI 0.34 to 0.88), but not at 12 to 24 months (2 studies, 83 children: RR 0.99, 95% CI 0.76 to 1.29) and may result in fewer infections (2 studies, 83 children: RR 0.14, 95% CI 0.03 to 0.72) (low certainty evidence). Cyclophosphamide compared to chlorambucil may make little or no difference in the risk of relapse after 12 months (1 study, 50 children: RR 1.31, 95% CI 0.80 to 2.13) (low certainty evidence).
AUTHORS' CONCLUSIONS
New studies incorporated in this review indicate that rituximab is a valuable additional agent for managing children with steroid-dependent nephrotic syndrome. However, the treatment effect is temporary, and many children will require additional courses of rituximab. The long-term adverse effects of this treatment are not known. Comparative studies of CNIs, MMF, levamisole and alkylating agents have demonstrated little or no differences in efficacy but, because of insufficient power; clinically important differences in treatment effects have not been completely excluded.
Topics: Adolescent; Alkylating Agents; Azathioprine; Child; Child, Preschool; Chlorambucil; Cyclophosphamide; Cyclosporine; Humans; Immunosuppressive Agents; Infant; Levamisole; Mycophenolic Acid; Nephrotic Syndrome; Prednisolone; Prednisone; Randomized Controlled Trials as Topic; Recurrence; Ribonucleosides; Rituximab; Secondary Prevention
PubMed: 32297308
DOI: 10.1002/14651858.CD002290.pub5 -
Strahlentherapie Und Onkologie : Organ... Jun 2020Whole lung irradiation (WLI) represents an important part of multimodal therapy in Ewing sarcoma (EwS) patients diagnosed with pulmonary metastases. This review...
Risk stratification of pulmonary toxicities in the combination of whole lung irradiation and high-dose chemotherapy for Ewing sarcoma patients with lung metastases: a review.
BACKGROUND
Whole lung irradiation (WLI) represents an important part of multimodal therapy in Ewing sarcoma (EwS) patients diagnosed with pulmonary metastases. This review discusses pulmonary toxicity in EwS patients with pulmonary metastases treated with WLI, who received different modes of high-dose chemotheray (HD-Cth).
METHODS
Literature was compiled using the Cochrane Library, PubMed database, and the National Institute of Health (NIH) clinical trials register. Relevant patient information, including nature of HD-Cth, acute and late lung toxicities, and pulmonary function disorders, was selected from the above databases.
RESULTS
Nine reports with a total of 227 patients, including 57 patients from a single randomized trial were included in this review. No acute or chronic symptomatic pulmonary toxicities were observed in patients that received WLI after HD busulfan-melphalan (HD-Bu/Mel), but 8% of these patients were diagnosed with asymptomatic restrictive lung disease. Grade 1 or 2 acute or chronic lung adverse effects were observed in up to 30% of patients that received WLI after HD treosulfan/Mel (HD-Treo/Mel) or HD etoposide (E)/Mel. Interstitial pneumonitis was present in 9% of patients treated concurrently with E/Mel and total body irradiation (TBI) with 8 Gy. Radiation doses as well as time between HD-Cth and WLI were both identified as significant risk factors for pulmonary function disorders.
CONCLUSION
The risk of adverse lung effects after WLI depends on several factors, including cumulative radiation dose and dose per fraction, HD-Cth regimen, and time interval between HD-Cth and WLI. A cumulative radiation dose of up to 15 Gy and a time interval of at least 60 days can potentially lead to a reduced risk of pulmonary toxicities. No evident adverse lung effects were registered in patients that received simultaneous therapy with HD-Cth and TBI. However, pulmonary function testing and lung toxicity reports were lacking for most of these patients.
Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Child; Combined Modality Therapy; Dose Fractionation, Radiation; Dose-Response Relationship, Radiation; Drug Administration Schedule; Etoposide; Female; Humans; Lung; Lung Diseases, Interstitial; Lung Neoplasms; Male; Melphalan; Procedures and Techniques Utilization; Radiation Pneumonitis; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated; Respiratory Function Tests; Risk; Sarcoma, Ewing; Whole-Body Irradiation; Young Adult
PubMed: 32166453
DOI: 10.1007/s00066-020-01599-8 -
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 -
Environmental Science and Pollution... Jan 2020Water contamination with pharmaceutical products is a well-studied problem. Numerous studies have demonstrated the presence of anticancer drugs in different water...
Water contamination with pharmaceutical products is a well-studied problem. Numerous studies have demonstrated the presence of anticancer drugs in different water resources that failed to be eliminated by conventional wastewater treatment plants. The purpose of this report was to conduct a systematic review of anticancer drugs in the aquatic environment. The methodology adopted was carried out in compliance with the PRISMA guidelines. From the 75 studies that met the specific requirements for inclusion, data extracted showed that the most common anticancer drugs studied are cyclophosphamide, tamoxifen, ifosfamide and methotrexate with concentrations measured ranging between 0.01 and 86,200 ng/L. There was significant variation in the methodologies employed due to lack of available guidelines to address sampling techniques, seasonal variability and analytical strategy. The most routinely used technique for quantitative determination was found to be solid-phase extraction followed by LC-MS analysis. The lowest reported recovery percentage was 11%, and the highest limit of detection was 1700 ng/L. This indicated the inadequacy of some methods to analyse anticancer drugs and the failure to obtain reliable results. The significant heterogeneity within methodologies made it difficult to compare results and draw conclusions, nevertheless, this study aids in the extrapolation of proposed recommendations to guide future studies and reviews. Graphical abstract.
Topics: Antineoplastic Agents; Chromatography, Liquid; Cyclophosphamide; Environmental Monitoring; Humans; Ifosfamide; Methotrexate; Pharmaceutical Preparations; Solid Phase Extraction; Tamoxifen; Wastewater; Water Pollutants, Chemical
PubMed: 31832963
DOI: 10.1007/s11356-019-07045-2