Efficacy of treatments in children with relapsed/refractory acute lymphocytic leukemia (r/r ALL).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e22001-e22001
Author(s):  
Amber L Martin ◽  
Simu K. Thomas ◽  
Mariana Cota ◽  
Yanni Hao ◽  
Younan Zhang ◽  
...  
Keyword(s):  
Childhood Leukemia ◽  
Pediatric Patients ◽  
Meta Analysis ◽  
Safety Data ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
Treatment Regimens ◽  
Pediatric All ◽  
New Treatments

e22001 Background: Pediatric ALL is the most common childhood leukemia, 20% of children relapse after initial complete response (CR) to first-line treatment and the 5-year overall survival (OS) of pediatric r/r ALL patients is only 30%. A systematic literature review (SLR) and meta-analysis (MA) were conducted to determine the effects of treatments for pediatric r/r ALL. Methods: EMBASE, MEDLINE, and CENTRAL databases were searched from 01/01/2000-12/31/2016 using keywords for r/r ALL paired with terms for pediatric patients and relevant treatments to identify studies reporting efficacy and safety data. Proceedings from 2015-2016 oncology conferences were also searched. Statistical analysis was limited to studies with comparable patient populations and treatment regimens. Random-effects MA of single-arm data were performed to determine the OS rate at 6 and 12 months, median OS, and the rate of CR (timepoint not reported) for pediatric r/r ALL patients treated with clofarabine + cyclophosphamide + etoposide (CCE). Results: The studies included in the review were heterogeneous and just five of the 46 studies identified by the SLR were similar enough for MA in terms of outcomes and populations (median age 8-14 years, median 2 prior lines of therapy). All five studies were single-arm studies evaluating CCE, a treatment with a pooled 6-month OS of 43.5% (95% CI: 32.6% - 55.1%), 1-year OS of 26.7% (95% CI: 17.5% - 38.3%), and pooled median OS of 5.2 (95% CI: 3.2 – 8.6) months. The CR rate was 43.2% (33.7% - 53.3%) across the five studies (timepoint not reported), and the rate was comparatively higher when analysis was limited to those with B-cell immunophenotype (56.3% [95% CI: 22.5% - 85.1%]). Conclusions: This is the first SLR and MA to be conducted on pediatric r/r ALL to date. Available evidence was heterogeneous and MA were only possible for single-arm trials examining CCE. Survival is poor in this population, as just over a quarter of patients receiving CCE were alive at 12 months, with median OS less than 6 months. CR rates were more promising but the lack of data on timepoint of assessment make the results difficult to interpret. New treatments are needed to better manage patients in this r/r population.

Determining the Benefits of Chemotherapy for Achieving Complete Response in Patients with Untreated Advanced Stage Follicular Lymphoma: A Systematic Review and Meta-Analysis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 290-290 ◽  
Author(s):  
Josiah N. Orina ◽  
Susan G. Moore ◽  
Mary Jo Lechowicz ◽  
Christopher R. Flowers
Keyword(s):  
Follicular Lymphoma ◽  
Watchful Waiting ◽  
Meta Analysis ◽  
Single Agent ◽  
Complete Response ◽  
Inclusion Criteria ◽  
First Line ◽  
Treatment Regimens ◽  
American Society ◽  
Meta Analyses

Abstract Background:Although advanced stage follicular lymphoma (FL) is considered incurable with standard therapy, and early institution of therapy has not demonstrated benefits over watchful waiting, novel strategies such as lymphoma vaccines and maintenance rituximab(R) provide opportunities for achieving prolonged disease-free intervals. Promoting the benefits of these strategies will depend upon improving the complete response rate(CR) with initial treatment. To date, the optimal first-line therapy remains undefined. To address this issue, we conducted a systematic literature review and meta-analyses comparing first-line chemotherapy regimens for FL. Methods:We searched the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 1, 2003), MEDLINE (1/1966–6/2005), EMBASE (1/1980–7/2005), American Society of Hematology Annual Meeting abstracts (2002–2004), and American Society of Clinical Oncology Annual Meeting abstracts (1995–2005). Each search used combinations of the term follicular lymphoma and terms for medications and treatment regimens. Criteria for including studies were: Inclusion of patients with untreated stage III/IV FL; Intervention with chemotherapy and/or immunotherapy, radioimmunotherapy, or watchful waiting; Reporting in English of the following treatment outcome measures for patients with FL: CR/CR-unconfirmed, overall response rate (OR), and at least one form of survival data. Extracted data included pre-treatment disease status, treatment regimen, median follow-up time, progression free survival, overall survival, CR and OR. The following treatment strategies from peer-review publications were analyzed: single-agent fludarabine(F), fludarabine-combinations(F-com), single-agent alkylators(A), alkylator-combinations (without anthracycline), and anthracycline-combinations. In meta-analyses of selected studies, we utilized the Mantel-Haenszel (fixed effects model) and DerSimonain and Laird (random effects) methods to calculate the risk difference comparing treatment regimens’ CR/CRu to the spontaneous CR in patients undergoing watchful waiting (4.6%; Ardeshna et al. Lancet, 2003). Results:Over 1800 abstracts were reviewed yielding 37 reported treatments that met inclusion criteria and included 2709 patients. The benefits of initial chemotherapy for achieving CR are shown in Figure 1. Single-agent F and A had similar benefits, as did F-com and CHOP. Substantial heterogeneity existed among other alkylator and anthracycline combinations limiting their ability to be combined using meta-analysis. Overall, chemotherapy provided a 49% improvement in the chances of attaining CR (95% CI:41%–57%). Meta-analyses of single agent R and RCHOP showed CR of 26% (95% CI:18%–34%) and 74% (95% CI:65%–83%) respectively (Figure 1B). Insufficient numbers of studies met inclusion criteria to examine the benefits of adding R to other regimens. Conclusions:CHOP and F-com provide the greatest likelihood of achieving CR in untreated FL. This benefit is even greater in CHOP patients who receive R. Selection of an initial regimen for patients with FL will depend on patient-specific factors and future plans for other therapies. Figure Figure

Abstract 16653: Ventricular Arrhythmias With Ibrutinib Use: A Systematic Review and Meta-Analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Yaser Khallid ◽  
Neethi Dasu ◽  
Ankit Shah ◽  
Michael G Fradley ◽  
Kirti Dasu ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Ventricular Arrhythmias ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Lymphocytic Leukemia ◽  
Duration Of Treatment ◽  
Treatment Regimens ◽  
Mantle Cell ◽  
Meta Regression ◽  
Meta Regression Analysis

Introduction: Ibrutinib is a widely used treatment option for patients with chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom’s macroglobulinemia. There is limited investigation on the relationship between ibrutinib and the development of ventricular arrhythmias. Hypothesis: We hypothesized that the incidence of ventricular arrhythmias in patients taking ibrutinib compared to the patients on other treatment regimens would be higher. Methods: We performed an aggregate data meta-analysis on nine studies to examine the incidence of ventricular arrhythmias. We further assessed a meta-regression analysis to evaluate the effect of duration of therapy on incidence of ventricular arrhythmias. Relative risk (RR) and 95% confidence intervals (CI) were estimated using a random-effects model. Results: Of 3809 patients being treated with ibrutinib, the incidence of ventricular arrhythmias was almost 8-fold higher in patients being treated with ibrutinib compared to other tyrosine kinase inhibitors (TKIs), other chemotherapies, or immunotherapy. (RR 8.13, 95% CI 4.37-15.10, p <0.0001). On meta-regression analysis, the incidence increased further with longer duration of treatment (coefficient = 0.0206, p=0.049); patient populations greater than 60 years have a higher incidence of ventricular arrhythmias (coefficient = 0.0237, p=0.044). Over 50% of patients diagnosed with ventricular arrhythmias on ibrutinib died of sudden death. Conclusions: For patients treated with ibrutinib, there was a markedly higher rate of ventricular arrhythmias and an increased incidence with longer duration of treatment. These data highlight the need for guidelines on surveillance and management for ventricular arrhythmias for patients taking ibrutinib.

Comparative Efficacy of First-Line Chemotherapy-Free Combinations in Chronic Lymphocytic Leukemia (CLL): A Network Meta-Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-26
Author(s):  
Philip A Haddad ◽  
Nowell Ganey ◽  
Kevin M. Gallagher
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
English Language ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Meta Analysis ◽  
The Elderly ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
Significant Difference ◽  
Anti Cd20

Introduction: Chronic Lymphocytic Leukemia (CLL) is an incurable B-cell malignancy which disproportionately affects the elderly. Although first-line chemoimmunotherapy (CIT) improved CLL clinical outcomes, recent randomized trials revealed superior outcomes with novel chemotherapy-free combinations (CFC) incorporating anti-CD20 monoclonal antibodies and inhibitors of BTK or Bcl-2. So far, these CFC have not been compared head-to-head. We conducted this network meta-analysis to evaluate their relative efficacy to each other. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language; diagnosis of CLL; trials that explored the efficacy of first-line CFC with Obinutuzumab (O), Rituximab (R), Ibrutinib (IB), Acalabrutinib (ACAL), Venetoclax (VEN) compared to standard CIT that included Chlorambucil (CHLOR) with either R or O, Bendamustine+Rituximab, or Fludarabine+ Cyclophosphamide+R; and phase 3 randomized studies reporting responses, progression, death, and adverse (AE) events. A frequentists network meta-analysis was conducted using netmeta package and random-effects model. Results: Five studies comprising a total of 2,272 participants were included. When O-based CFC data was analyzed, only ACAL-O had a significant lower relative risk (RR) of progression and death (P&D). There were no significant differences with respect to overall response rates (ORR), complete remission (CR), minimal residual disease (MRD), or grade &gt;3 adverse events (Grd3+) among O-based CFC. When R-based CFC data was analyzed, IB and IB-R were not different with respect to RR of P&D, ORR, CR, MRD, or Grd3+. When the data was analyzed as CFC versus combined CIT, only ACAL-O was found to be significantly superior to other O- and R-based CFC with respect to RR of P&D. ORR and Grad3+ rates of O- and R-based CFC were not significantly different. While ACAL-O, IB-O, and VEN-O had superior CR and MRD rates compared to other CFC, there were no significant differences among each other. Conclusions: This network meta-analysis is the first to compare and rank first-line CFC therapies in CLL. It indicates that ACAL-O has a superior profile having the lowest RR of P&D without significant difference in Grd3+ among CFC. Disclosures No relevant conflicts of interest to declare.

Determining the Benefits of Rituximab + Chemotherapy for Patients with Untreated Follicular Lymphoma: A Comprehensive Meta-Analysis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3330-3330 ◽  
Author(s):  
Josiah N. Orina ◽  
Christopher R. Flowers
Keyword(s):  
Follicular Lymphoma ◽  
Watchful Waiting ◽  
Meta Analysis ◽  
Single Agent ◽  
Inclusion Criteria ◽  
First Line ◽  
Treatment Regimens ◽  
First Line Therapy ◽  
American Society ◽  
Meta Analyses

Abstract Background: Current guidelines offer numerous options for initiating therapy in patients with untreated, advanced stage follicular lymphoma (FL). Selecting among these options that include watchful waiting, single-agent and combination chemotherapy, monoclonal antibodies, and radioimmunotherapy, remains challenging. Recent data suggest that chemotherapy combined with a monoclonal antibody may alter patterns of relapse and overall survival for pts with FL (Fisher, Blood 2004). While rituximab (R) chemotherapy combinations have become commonly used for untreated pts with FL, to date, the optimal first-line therapy remains undefined. To address this issue, we updated a systematic literature review and performed a meta-analysis of first-line therapy for untreated FL that examined the effect of various chemotherapy regimens combined with R on response rates and survival in patients with untreated FL. Methods: The comprehensive systematic review included searches the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 1, 2003), MEDLINE (1/1996–6/2006), EMBASE (1/1980–7/2006), American Society of Hematology Annual Meeting abstracts (2002–2005), and American Society of Clinical Oncology Annual Meeting abstracts (1995–2006). Each database was searched using combinations of the term follicular lymphoma and the terms for medications and treatment regimens. Inclusion criteria for studies were as follows: 1) Inclusion of patients with untreated stage III/IV FL grades 1, 2, or 3; 2) Intervention with chemotherapy and/or immunotherapy, radioimmunotherapy, or watchful waiting; 3) Reporting in English of the following treatment outcome measures specifically for patients with FL: CR/CR-unconfirmed, overall response rate (OR), and at least one form of survival data. Abstracts subsequently published as papers were excluded. Extracted data included pre-treatment disease status, treatment regimen, median follow-up time, progression free survival, overall survival, CR and OR. The following treatment strategies from peer-review publications were analyzed: single agent R, R-CVP, R-CHOP, and fludarabine-combinations with R (R-Fcom). In meta-analyses of selected studies, we utilized the Mantel-Haenszel (fixed effects model) and DerSimonain and Laird (random effects) methods to calculate the risk difference comparing treatment regimens’ CR/CRu to the spontaneous CR in patients undergoing watchful waiting (4.6%; Ardeshna et al. Lancet, 2003). Results: In total, over 3135 abstracts were reviewed to identify 11 studies meeting the inclusion criteria for this analysis. These studies included data from 3144 patients. Only one study presenting CR data for R-CVP (36%, 95% confidence interval: 28%–44%) met inclusion criteria. The meta-analyses estimated the CR rate associated with single-agent R to be 30% (95% CI: 20%–40%), R-CHOP to be 62% (30%–94%), and R-Fcom to be 85% (76%–94%) (random effects; see Figure). Conclusions: R-CHOP and R-fludarabine combinations appear to produce the highest CR rates for untreated pts with FL. Meta-analysis can aid clinicians in therapeutic decision making as they weight the risks and benefits of various regimens for newly diagnosed pts. Figure Figure

Indirect Comparison of the Efficacy of Melphalan-Prednisone-Bortezomib Relative to Melphalan-Prednisone-Thalidomide and Melphalan-Prednisone for the First Line Treatment of Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2367-2367
Author(s):  
Yating Yeh ◽  
James Chambers ◽  
Sabine Gaugris ◽  
Jeroen Jansen
Keyword(s):  
Multiple Myeloma ◽  
Meta Analysis ◽  
Indirect Comparison ◽  
Complete Response ◽  
Similar Efficacy ◽  
Line Treatment ◽  
Relative Efficacy ◽  
First Line ◽  
Overall Response ◽  
First Line Treatment

Abstract Melphalan-prednisone (MP) combination has been considered a standard of care for front line treatment of multiple myeloma in patients non eligible for transplant. Melphalan-prednisone-bortezomib (MPV) combination has been approved in the United States in patients non eligible for high-dose chemotherapy (HD-C) and has recently received a positive opinion from the CHMP in Europe. Melphalan-prednisone-thalidomide (MPT) was approved in Europe in patients &gt;65 or not eligible for HD-C. There is no head-to-head trial directly comparing MPV to MPT. The objective of the current study was to compare the efficacy of MPV to MP and MPT as first line treatment of multiple myeloma in patients non eligible for transplant. Six randomized placebo controlled trials investigating the efficacy of MPT (5) and MPV (1) relative to MP were identified with a systematic literature review. The endpoints of interest were overall survival (OS), progression free survival (PFS) and overall and complete response. Relative efficacy estimates of MPT versus MP as obtained from the MPT-MP trials were combined with meta-analysis techniques and simultaneously indirectly compared with the relative efficacy of MPV versus MP from the MPV-MP trial (VISTA). This adjusted indirect comparison was performed with Bayesian fixed and random effects models. As compared to frequentist approach, Bayesian meta-analysis offers a more informative summary of the likely value of efficacy after observing the data and allows for direct probabilistic inferences. Of the three interventions compared, there was an 81% probability that MPV was the most efficacious intervention in terms of overall response and a &gt;99% probability in terms of complete response. With MPV a patient was two times more likely to show a complete response than with MPT (Relative Risk=2.15; 95%Credible Interval (CrI): 0.99–4.45). Both MPV and MPT showed greater OS than MP (HR=0.61; 95%CrI: 0.42–0.88 and HR=0.61; 95%CrI: 0.47–0.78 respectively); the indirect comparison showed similar efficacy in terms of OS between MPV and MPT (MPV vs MPT: Hazard Ratio=1.00; 95%CrI 0.64–1.57). Both MPV and MPT also displayed greater PFS than MP (MPV versus MP: HR=0.61; 95%CrI 0.49–0.76 and MPT versus MP HR=0.51; 95%CrI 0.41–0.63 respectively) and showed similar efficacy (MPV vs MPT: HR=1.19; 95%CrI: 0.87–1.63). In this study, both MPV and MPT are more efficacious than MP in terms of response, PFS and OS. MPV is expected to result in a greater complete and overall response than MPT. No difference in OS or PFS was displayed. Further analyses will need to be undertaken once evidence base data is more mature.

scholarly journals Time to Next Treatment, Healthcare Resource Utilization, and Healthcare Costs Among Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Following First-Line Ibrutinib

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4016-4016
Author(s):  
Swetha Challagulla ◽  
Bruno Emond ◽  
Raisa R. Volodarsky ◽  
Alex Young ◽  
Ameur Manceur ◽  
...  
Keyword(s):  
Healthcare Costs ◽  
Healthcare Resource ◽  
Healthcare Resource Utilization ◽  
Lymphocytic Leukemia ◽  
Emergency Room Visits ◽  
Small Lymphocytic Lymphoma ◽  
Publicly Traded ◽  
First Line ◽  
Treatment Regimens ◽  
Outpatient Visits

Abstract Background: Ibrutinib is an oral once-daily Bruton's tyrosine kinase inhibitor (BTKi) and is the only targeted treatment that has demonstrated significant progression-free survival (PFS) and overall survival (OS) benefit in multiple phase 3 trials for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). With ibrutinib established as a preferred first-line (1L) treatment option, it is important to better understand the treatment sequence after 1L ibrutinib and the characteristics of patients who are treated with a second-line (2L) therapy. Using a real-world US administrative claims database, this study aimed to compare time to next treatment (TTNT), healthcare resource utilization (HRU), and healthcare costs between different 2L treatment regimens (cohorts) used after ibrutinib. Methods: Adults with CLL/SLL treated with 1L ibrutinib were identified in a US claims database (Optum's de-identified Clinformatics ® Data Mart Database; 02/12/2013-03/31/2020). Those receiving a 2L therapy were considered eligible for the study. Retreatment with ibrutinib, in-class switch to another BTKi, or treatment with anti-CD20 immunotherapy-only were not considered eligible 2L treatment options for this evaluation. The most commonly used treatment regimens were categorized into the following clinically-relevant treatment cohorts: 1) chemoimmunotherapy (CIT) or chemotherapy (CT)-only, and 2) venetoclax (VEN)- or idelalisib (IDELA)-based regimens (monotherapy or combination regimens). Comparisons of TTNT, HRU (inpatient admissions, outpatient visits, emergency room visits, other ancillary services), and per patient per month healthcare costs (inpatient admissions, outpatient visits, emergency room visits, other ancillary services, pharmacy) were evaluated based on the sum of the payer and patient paid amount during 2L treatment. Comparisons were adjusted using multivariate regression including confounders observed in the baseline period and during 1L ibrutinib therapy. For costs and HRU, 95% confidence intervals and p-values were obtained from 499 bootstrap resamples. Results: A total of 132 CLL/SLL patients who received ibrutinib as a 1L treatment and had a subsequent eligible 2L therapy were included; mean age was 74 years old, 64% were male. Eligible patients received 2L CIT/CT-only (63/132, 48%), or VEN/IDELA-based regimens (69/132, 52%). TTNT was significantly longer for 2L VEN/IDELA-based regimens than for CIT/CT (hazard ratio at 12 months: 0.37; P=0.0337) (Figure 1). The number of outpatient visits for antineoplastic drug administration was significantly lower for patients receiving 2L VEN/IDELA-based regimens compared to CIT/CT (rate ratio=0.44; P=0.004). Total mean monthly healthcare cost (includes CLL/SLL and non-CLL/SLL-related medical/pharmacy costs) was $1,754 higher, but not significantly different (P=0.593), for patients receiving VEN/IDELA-based regimens compared with CIT/CT (Figure 2). Total mean monthly medical cost (non-pharmacy) was significantly lower ($-5,202; P=0.036) for patients receiving VEN/IDELA-based regimens compared to CIT/CT (Figure 2). Conclusions: This study demonstrates that VEN/IDELA-based regimens may be a more viable treatment option post-1L ibrutinib use for CLL/SLL patients compared to CIT/CT. When compared to 2L CIT/CT, use of VEN/IDELA-based regimens post-1L ibrutinib use was associated with significantly longer TTNT and lower medical costs, signifying reduced disease burden to the patients and lessened burden to the healthcare system. These findings also suggest that treatment convenience associated with 2L oral targeted regimens may play an important role in improving treatment outcomes. These results support the need for evaluating treatment sequencing strategies in the real-world setting to further improve clinical outcomes and reduce the burden of total cost of care for patients with CLL/SLL. Figure 1 Figure 1. Disclosures Challagulla: Pharmacyclics LLC, an AbbVie Company: Current Employment; AbbVie: Current equity holder in publicly-traded company. Emond: Janssen: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy; GlaxoSmithKline: Consultancy. Volodarsky: Pharmacyclics LLC, an AbbVie Company: Current Employment; AbbVie: Current equity holder in publicly-traded company. Young: AbbVie: Current equity holder in publicly-traded company; Pharmacyclics LLC, an AbbVie Company: Current Employment. Manceur: AbbVie: Consultancy; Actelion, part of the Janssen Pharmaceutical Companies of Johnson & Johnson: Consultancy; Bristol-Myers Squibb: Consultancy; Daiichi-Sankyo: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy. Karve: AbbVie: Current Employment, Current equity holder in publicly-traded company.

scholarly journals “Subtherapeutic concentrations of first-line antitubercular agents in pediatric patients and its association with tuberculosis treatment outcome: protocol for a systematic review and meta-analysis”

2020 ◽  
Author(s):  
Jorge Chachaima-Mar ◽  
Diana Sánchez-Velazco ◽  
Cesar Ugarte-Gil
Keyword(s):  
Systematic Review ◽  
Pediatric Patients ◽  
Conflicts Of Interest ◽  
Data Extraction ◽  
Meta Analysis ◽  
Serum Levels ◽  
Reference Ranges ◽  
Antitubercular Agents ◽  
First Line ◽  
Antitubercular Drugs

AbstractPediatric tuberculosis is a neglected disease that is receiving more attention lately. Some studies found that serum levels of first line antituberculosis drugs do not reach reference concentrations in children. However, these reference ranges were validated in an adult sample. Thus, we do not know if subtherapeutic concentrations of antitubercular agents in children are associated with negative outcomes.ObjectiveTo estimate the association between subtherapeutic concentrations of first-line antitubercular drugs with clinical outcomes of treatment.MethodsWe propose to do a systematic review and meta-analysis. In order to do so, we will perform an electronic search in Medline, SCOPUS, Web of Science and Global Index Medicus. There will be no restriction of language nor date of publication. First, we will screen titles and abstracts; then we will screen through the full text of the article. Both phases will be done by 2 independent authors. Data extraction will be performed using a data abstraction form by two independent authors. The quality of the studies will be checked with standardized tools according to the design of the study, and will also be performed by duplicate. We will present the main characteristics of each included study through tables. The heterogeneity between studies will be assessed through the I2 statistic. If appropriate, we will use the random-effects model to calculate the pooled estimate. We will evaluate the publication bias through visual inspection of the funnel plot and Egger’s test. Pre-arranged subgroup and sensitivity analysis will be performed.ResultsWe will publish the results of this systematic review in a peer-reviewed journal.ConclusionsThis systematic review will provide up-to-date evidence regarding serum concentration in pediatric patients and its association with outcomes. With the analysis we plan, we will offer important recommendations regarding the dosage of the first line antitubercular agents in children, and the modifications that may be needed.Conflicts of interestAll the authors declare to have no conflict of interest.FundingThis study did not receive funding from the public, commercial or not-for-profit sectors.

A single institutional experience of 261 patients with large granular lymphocytic leukemia (LGLL).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7555-7555
Author(s):  
Magali Van den Bergh ◽  
Leidy Lismeri Isenalumhe ◽  
Emilie Wang ◽  
Braydon Schaible ◽  
Zhenjun Ma ◽  
...  
Keyword(s):  
Nk Cell ◽  
Cell Lineage ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Treatment Modalities ◽  
Categorical Variables ◽  
Cancer Center ◽  
First Line ◽  
Exact Test ◽  
Significant Difference

7555 Background: LGLL is a rare clonal lymphoproliferative disorder of post-thymic T-cell or natural killer (NK)-cell lineage associated with cytopenias, splenomegaly, autoimmune disorders, and recurrent mucocutaneous infections. Treatment is dictated by the presence of these manifestations and consists of immunosuppressive therapy. Methods: This is a retrospective analysis of clinical and laboratory features, treatment modalities, and outcomes of LGLL patients evaluated at Moffitt Cancer Center between 1995 and 2016. Continuous and categorical variables were tested via Kruskal-Wallis ANOVA and Fisher’s Exact Test. Kaplan-Meier curves were used for overall survival (OS). P-values were two-sided with significance set at < 0.05. Results: We identified 261 patients with LGLL (91.6% T, 8.4% NK). Median age was 66 years [21-90] and M:F ratio 1.2:1. Median follow up was 3.07 years [0-21.88]. 42.9% presented with anemia, 37.1% neutropenia, 30.7% thrombocytopenia, 29.1% bicytopenia and 6.9% pancytopenia. Transfusion dependence was noted in 20.3%, splenomegaly in 27.2% and bone marrow (BM) involvement in 69.3%. 24.9% had autoimmune diseases and 9.2% autoimmune cytopenias. 45.6% were observed while the remainder required at least 1 line of therapy. 5-yr and 10-yr OS were 75.0% and 63.1% respectively. There was no statistically significant difference in OS, complete response or duration of response based on first line agent (methotrexate, cyclophosphamide, cyclosporine A). However, there was a statistically significant improved partial response with methotrexate versus other therapies (p=0.01). A marginally significant association between severe anemia/transfusion dependence and poor overall response rate (p=0.075) to any therapy was noted. There was no statistically significant difference in OS based on absolute LGL count. Mean number of therapies was 1.08 (range 0-6) and was higher in those with LGL count <0.5 k/μL (p=0.0078), BM involvement (p<0.0001), and splenomegaly (p<0.0001). Conclusions: In this large retrospective study, we described the frequency of LGLL-associated manifestations and their impact on the course of LGLL. We confirmed that there is no difference in OS among first line therapies.

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