High Dose Chemotherapy and Autologous Stem Cell Transplantation in the Primary Therapy of Advanced Follicular Lymphoma in Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2314-2314
Author(s):  
Murtadha K. Al-Khabori ◽  
John de Almeida ◽  
Gordon Guyatt ◽  
John Kuruvilla ◽  
Michael Crump
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
P Value ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
American Society

Abstract Abstract 2314 Poster Board II-291 Background: The impact of high dose therapy and autologous stem cell transplantation (ASCT) in the upfront management of adults with advanced follicular lymphoma (FL) on overall survival remains uncertain. A number of randomized clinical trials (RCTs) compared ASCT to conventional dose chemotherapy regimens. We performed a systematic review to address this question. Objective: To compare the overall survival (OS), event free survival (EFS), treatment related mortality (TRM), incidence of secondary myelodysplasia/acute myeloid leukemia (t-MDS/AML) and secondary solid tumors within the ASCT strategy and chemotherapy. Methods: We performed a search of MEDLINE, EMBASE, CENTRAL, American Society of Hematology (ASH), American Society of Clinical Oncology (ASCO), BIOSIS, PAPERSFIRST, PROCEEDINGS, clinical trials registries (National Cancer Institute, clinicaltrials.gov) and bibliographies of relevant studies for randomized controlled trials comparing myelo-ablative chemotherapy with ASCT to any chemotherapy in adults with untreated advanced (Ann Arbor stage III-IV) FL. Two reviewers recorded study characteristics, methodology and outcomes. Disagreement was resolved by discussion. Results: Seven trials were identified and included in the systematic review but only four with available data reporting 941 patients were included in the meta-analysis. Three trials excluded: one was never reported; the second was stopped early due to the increased toxicities in the transplant arm; and the third showed no significant difference in EFS or OS at an interim analysis with insufficient data for the meta-analysis. None of these studies has been published. In one of the 7 trials patients in both arms received rituximab during the induction treatment. High dose therapy and ASCT did not result in improved OS compared to standard therapy, Hazard Ratio (HR) 1.15 (0.85, 1.55). The HR for EFS was 0.61 (0.34, 1.11) with substantial heterogeneity, I2 =91%, Chi2 p value <0.00001. Only the duration of the follow up could explain this heterogeneity with statistically significant subgroup interaction, P <0.00001. The incidence of t-MDS/AML ranged from 1% to 7% in the ASCT arms of the four studies, with a difference in favour of standard chemotherapy, Risk Difference (RD) 4% (95%CI: -1%, 8%), and significant heterogeneity (Chi2 p value of 0.008, I2=75%) due to difference in duration of follow up (p=0.005 for the subgroup differences).There was no increase in mortality directly attributable to treatment (RD 0%, 95%CI: -2%, 1%) nor in secondary solid tumors (RD 1%, 95%CI: -2%, 4%). Conclusions: High dose therapy and ASCT as part of initial does not improve overall survival despite a trend towards better disease control, likely because of the effectiveness of second and subsequent lines of treatment for FL. T-MDS/AML occurs more commonly following ASCT and represents a significant risk to patients. With one exception, these studies were conducted before the introduction of monoclonal B cell antibodies. Future trials of ASCT in the context of current chemo-immunotherapy approaches to FL would further inform this issue. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Value of PD-L1 Expression as Predictive Biomarker in Metastatic Renal Cell Carcinoma Patients: A Meta-Analysis of Randomized Clinical Trials

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1945 ◽  
Author(s):  
Alberto Carretero-González ◽  
David Lora ◽  
Isabel Martín Sobrino ◽  
Irene Sáez Sanz ◽  
María T. Bourlon ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Clinical Trials ◽  
Renal Cell ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Standard Of Care ◽  
Predictive Biomarker ◽  
P Value ◽  
Metastatic Rcc

Immune checkpoint inhibitors (ICIs) are soluble antibodies that have dramatically changed the outcomes including overall survival in a subset of kidney tumors, specifically in renal cell carcinoma (RCC). To date, there is no a single predictive biomarker approved to be used to select the patients that achieve benefit from ICIs targeting. It seems reasonable to analyze whether the programmed death-ligand 1 (PD-L1) expression could be useful. To assess the role of PD-L1 expression as a potential predictive biomarker for benefit of ICIs in RCC patients, we performed a search of randomized clinical trials (RCTs) comparing ICIs (monotherapy or in combination with other therapies) to standard of care in metastatic RCC patients according to PRISMA guidelines. Trials must have included subgroup analyses evaluating the selected outcomes (progression-free survival (PFS) and overall survival (OS)) in different subsets of patients according to PD-L1 expression on tumor samples. Hazard ratios with confidence intervals were used as the measure of efficacy between groups. A total of 4635 patients (six studies) were included (ICIs arm: 2367 patients; standard of care arm: 2268 patients). Globally, PFS and OS results favored ICIs. Differential expression of PD-L1 on tumor samples could select a subset of patients who could benefit more in terms of PFS (those with higher levels; p-value for difference between subgroups: <0.0001) but it did not seem to impact in OS results (p-value for difference: 0.63). As different methods to assess PD-L1 positivity were used among trials, this heterogeneity could have an influence on the results. PD-L1 could represent a biomarker to test PFS in clinical trials but its value for OS is less clear. In this meta-analysis, the usefulness of PD-L1 expression as a predictive biomarker to select treatment in metastatic RCC patients was not clearly shown.

scholarly journals The Effects of Dairy Intake on Insulin Resistance: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2237 ◽  
Author(s):  
Kristen M. Sochol ◽  
Tanya S. Johns ◽  
Rupinder S. Buttar ◽  
Lovepreet Randhawa ◽  
Edeline Sanchez ◽  
...  
Keyword(s):  
Systematic Review ◽  
Insulin Resistance ◽  
Clinical Trials ◽  
Body Weight ◽  
Waist Circumference ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
P Value ◽  
Low Fat ◽  
Dairy Intake

The incidence of type 2 diabetes mellitus (DM) has increased in the US over the last several years. The consumption of low-fat dairy foods has been linked with decreasing the risk of DM but studies have yet to show a clear correlation. We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) evaluating the effects of dairy intake on homeostatic model assessment of insulin resistance (HOMA-IR), waist circumference, and body weight. In MEDLINE and Embase, we identified and reviewed 49 relevant RCTs: 30 had appropriate data format for inclusion in the meta-analysis. Using the Review Manager 5 software, we calculated the pooled standardized mean differences comparing dairy dietary interventions to control for our outcomes of interest. For HOMA-IR (794 individuals), we found a mean difference of −1.21 (95% CI −1.74 to −0.67; p-value < 0.00001; I2 = 92%). For waist circumference (1348 individuals), the mean difference was −1.09 cm (95% CI 1.68 to −0.58; p-value < 0.00001; I2 = 94%). For body weight (2362 individuals), the dairy intake intervention group weighed 0.42 kg less than control (p-value < 0.00001; I2 = 92%). Our findings suggest that dairy intake, especially low-fat dairy products, has a beneficial effect on HOMA-IR, waist circumference, and body weight. This could impact dietary recommendations to reduce DM risk.

scholarly journals Reduced-Intensity Versus Myeloablative Conditioning for Allogeneic Hematopoietic Cell Transplantation in Patients with Myelodysplastic Syndrome: A Systematic Review and Meta-Analysis of Randomized Clinical Trials & Cohort Studies

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-26
Author(s):  
Arshia Akbar ◽  
Zunairah Shah ◽  
Muhammad Ali Aziz ◽  
Muhammad Yasir Anwar ◽  
Saman Bahram ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Myelodysplastic Syndrome ◽  
Cohort Studies ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Chronic Gvhd ◽  
P Value ◽  
Grade 3 ◽  
Risk Of Relapse

Background: Conditioning regimen given before allogeneic hematopoietic stem cell transplantation (allo-HSCT) contributes significantly to the outcomes following transplant for myelodysplastic syndrome (MDS). Myeloablative conditioning (MAC) regimens are often associated with a lower risk of relapse; however, their use is often limited by toxicity and a higher risk of non-relapse mortality (NRM). Reduced-intensity conditioning (RIC) regimens are associated with a higher risk of relapse, a lower NRM, a lower incidence of graft versus host disease (GVHD), and hence is feasible in patients with advanced age or comorbidities. This study highlights the importance of the difference between the two interventions used in allo-HSCT for myelodysplastic syndrome (MDS). Methods: We conducted a comprehensive literature search using PubMed, Clinicaltrial.gov, Embase, Cochrane, and Web of Science on 5th May 2020 with no restriction of language or period. Initial research revealed 1698 articles. After excluding review articles, duplicates, and non-relevant articles, we included two randomized clinical trials and three cohort studies, which reported overall survival (OS), relapse-free survival (RFS), relapse incidence (RI), and incidence of acute and chronic (GVHD). Based on inclusion criteria, two randomized clinical trials (BMT CTN 0901 Trial Scott et al. 2017 & EBMT RICMAC Trial Kroger et al. 2017) and three cohort studies (BBMT 55226 Park et al. 2018, BBMT Orozco et al. 2019, BMT Alatrash et al. 2019) were included. Results: Among combined MDS and acute myeloid leukemia (AML) patients (n=1188) enrolled in 5 studies, 651 patients had MDS. Patients underwent MAC (n=484) or RIC (n=692) followed by either a matched related donor (MRD), n=236, or matched unrelated donor (MUD), n=236, allo-HCT. The median age range at the time of transplant was 50-54 years The use of RIC causes statistically non-significant trend of improved overall survival (OS) (OR 1.11: 95% CI: 0.74-1.67, p-value= 0.61) along with more risk of relapse incidence (RI) (R 1.34: 95% CI: 0.56-3.18, p value= 0.51), and reduced relapse free survival (RFS) (OR 0.88, 95% CI: 0.55-1.44: p value= 0.59). Differences were found in terms of safety of both conditioning regimens. MAC allo-HCT have more acute GVHD, grade 3 and 4 (OR 0.66: 95% CI: 0.29-1.52, p value= 0.33) and chronic GVHD, grade 3 and 4 (OR 0.72: 95% CI: 0.41-1.27: p value= 0.26) and treatment-related mortality (TRM) (OR 0.83, 95% CI: 0.37-1.86, p value= 0.65). The meta-analysis results are shown in figure-1. Conclusion: In adult MDS patients undergoing allo-HSCT, RIC is associated with improved overall survival, but at the cost of reduced RFS, and a higher risk of relapse. MAC, on the other hand, is associated with more treatment-related mortality and GVHD. Results of our analysis point out these trends but these are not statistically significant Figure 1 Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Maternal and Neonatal Effect of Fentanyl as a Premedication before Induction of General Anesthesia in Cesarean Surgery: A Systematic Review and Meta-analysis of Randomized Clinical Trials

2019 ◽  
Vol 15 (4) ◽  
pp. 232-237
Author(s):  
Mir Hadi Musavi ◽  
Behzad Jodeiri ◽  
Keyvan Mirnia ◽  
Morteza Ghojazadeh ◽  
Zeinab Nikniaz
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Cesarean Section ◽  
General Anesthesia ◽  
Apgar Score ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Intravenous Fentanyl ◽  
Neonatal Effect ◽  
Fentanyl Group

Background: Although, some clinical trials investigated the maternal and neonatal effect of fentanyl as a premedication before induction of general anesthesia in cesarean section, to the best of our knowledge, there is no systematic review to summarize these results. Objectives: The present systematic review and meta-analysis evaluated the maternal and neonatal effect of intravenous fentanyl as a premedication before induction of general anesthesia in cesarean section. Methods: The databases of Pubmed, Embase, Scopus and Cochrane library were searched till July 2017 to identify randomized clinical trials which evaluated the effects of intravenous fentanyl as a premedication before induction of general anesthesia compared with placebo on neonate first and fifth minute Apgar score and maternal heart rate and mean arterial pressure (MAP) in cesarean section. Standard Mean difference (SMD) was calculated and I-square statistic test was used for heterogeneity analysis. Results: The present systematic review and meta-analysis consisted of three clinical trials including 180 women in labor. Considering the results of meta-analysis, there is no significant differences between fentanyl and placebo in the case of Apgar score at 1 minute; however, the Apgar score of 5 minutes was significantly lower in fentanyl group compared with placebo (SMD -0.68, 95%CI: - 0.98, -0.38, p<0.001). In the term of maternal hemodynamics, the heart rate (SMD -0.43, 95%CI: - 0.72, -0.13, p=0.004) and MAP (SMD -0.78, 95% CI: -1.09, -0.48, p<0.001) in fentanyl group were significantly lower compared with placebo group. Conclusion: The present meta-analysis showed that using intravenous fentanyl as a premedication before induction of general anesthesia had adverse effects on neonate Apgar score. However, it had positive effects on preventing adverse consequences of intubation on maternal hemodynamics.

Sign in / Sign up

Export Citation Format

Share Document