To see the other types of publications on this topic, follow the link: Educational Bureau.
Journal articles on the topic 'Educational Bureau'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Educational Bureau.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Steudeman, Michael J. "From Civic Imperative to Bird's-Eye View: Renegotiating the Idioms of Education Governance during the Reconstruction Era." History of Education Quarterly 58, no. 2 (April 13, 2018): 199–228. http://dx.doi.org/10.1017/heq.2018.3.
Full textAbstract:
The nineteenth-century debate about the role of the US Bureau of Education was marked by negotiations between the civic republican language of antebellum common school advocacy and a social scientific language of educational professionalism. To advance this argument, this essay traces how members of Congress defined, criticized, and delimited the Bureau's institutional role between 1865 and 1872. First, avoiding calls for direct federal intervention, the Bureau's initial congressional advocates defined the Bureau as a vehicle for indirect influence on the states through the use of data and statistics. Second, after the Bureau's founding, its legislative critics used rhetoric to chastise and question both the Bureau's comprehensive vision and power. Finally, beginning with Commissioner John Eaton's tenure in 1870, the Bureau's functions were narrowed. Due to Eaton's reimagining of the Commissioner role, further congressional critique, and failed efforts to expand Bureau authority, the Bureau eventually became a government-sanctioned purveyor of social scientific expertise—one with little direct authority to intervene in education.
2
Tardy, Anne. "Dans le bureau du juge." Enfances & Psy 23, no. 3 (2003): 55. http://dx.doi.org/10.3917/ep.023.0055.
Full text
3
Dix, Guus. "Microeconomic forecasting: Constructing commensurable futures of educational reforms." Social Studies of Science 49, no. 2 (March 18, 2019): 180–207. http://dx.doi.org/10.1177/0306312719837364.
Full textAbstract:
According to economists from the Netherlands Bureau for Economic Policy Analysis, the introduction of performance pay for primary and secondary school teachers would lead to an increase in Dutch GDP of one-and-a-half percent in 2070. A new epistemic practice of microeconomic forecasting undergirded this attempt to make the distant future part of the political present. Taking the construction of the economic growth potential of performance pay as a starting point, this article analyzes how microeconomic forecasting emerged in one of the world’s oldest forecasting bureaus – and to what consequences. First, it highlights the institutional preconditions for this ‘turn to micro’ in an institution that had pioneered in the field of macroeconomic forecasting. Second, the article analyzes microeconomic forecasting as a distinct epistemic practice that brings different forms of economic expertise together to make the future of educational reforms commensurable. Finally, it analyzes the political consequences of this new epistemic practice in the sense that it not only enables but simultaneously limits the provision of policy-relevant evidence. Beyond the specificities of the case, the article contributes to the sociological study of economic policy devices against the background of a predominant market bias in the STS research on economics.
4
Taylor, John. "Luncheon Address — Children's Bureau." Children Australia 11, no. 1 (1986): 23. http://dx.doi.org/10.1017/s0312897000015599.
Full text
5
Ahmedzai, Sam H., John A. Snowden, Angela Cox, David A. Cairns, Cathy D. Williams, Anna Hockaday, Jamie Cavenagh, et al. "Patient-Reported Outcomes (PRO) in the Setting of Relapsed Myeloma: The Influence of Treatment Strategies and Genetic Variants Predict Quality of Life and Pain Experience." Blood 126, no. 23 (December 3, 2015): 3180. http://dx.doi.org/10.1182/blood.v126.23.3180.3180.
Full textAbstract:
Abstract Introduction. The impact of therapy in the management of disease relapse in patients with myeloma (MM) needs to be balanced with the impact on quality of life (QoL). The benefit of a salvage autologous stem cell transplant (ASCT2) has been demonstrated in terms of durability of response over non-transplant consolidation (NTC) (G Cook, et al., Lancet Oncology, 2013 Vol. 15, No. 8, p874-885). However, the impact of ASCT2 on patient reported outcomes (PRO) has not been reported to date. Therefore, patients' experience of pain and global measures of QoL, as part of a systematic assessment of PRO were measured at key points before, during and after randomisation in this multi-centre national phase III trial. Methods. 174 patients were randomised and data are presented on 171 who completed self-rated QoL assessments using EORTC QLQ-C30 and the EORTC myeloma module (MY-20). Pain assessments using BPI-SF were also incorporated. Genomic DNA was prepared from PBMNC using standardised GLP methods. Results. Completion rates for EORTC QoL and BPI-SF assessments were 83.3% and 77.1% at registration, and 59.6% and 53.8% at randomisation, respectively. Over half of patients reaching 1 year post-randomisation completed both assessments. EORTC QoL and BPI-SF forms had average 6% and 10% missing data, respectively. These completion rates are commensurate with previous longitudinal studies. EORTC QLQ-C30 Global health status/QoL subscale scores were significantly higher (better) in the NTC arm at 100 days and 6 month post-randomisation (P=0.0496), but not at later time points. BPI-SF pain scores showed significantly higher pain severity in the NTC (4.3/10) than the ASCT2 (2.9/10) patients only at 2 years post-randomisation. However, for pain interference with aspects of daily living, NTC patients reported significantly lower scores at 6 months (P=0.0155), 1 year post-randomisation (P=0.0466) and 2 years post-randomisation (P=0.0348). The MY-20 assessment showed that at 100 days and 6 months post-randomisation, the subscale scores for Side-effects of treatment were significantly higher in the ASCT2 arm than in the NTC arm, but not at later time points up to 2 years. Kaplan-Meier estimate of time-to-progression (TTP) by randomised allocation suggested that patients with an EORTC global QoL score greater than median (ie better QoL) at randomisation and who received ASCT2 had a significant TTP advantage over those receiving NTC (HR 0.3 (95% CI 0.15-0.61), p=0.006). However, with multivariate Cox regression analysis accounting for stratification factors this difference was not significant. Patients who reported a lower (ie better) than median level of concern on the Side-effects of treatment subscale and who received ASCT2 had a significant TTP advantage over those receiving NTC (Kaplan-Meier HR 0.24 (95% CI (0.10-0.55), p=0.003). This survival difference was still observed after multivariate Cox regression analysis (HR 5.02 (95% CI 1.00-25.20), p= 0.0499). We tested for genomic associations of SNPs from key genes reported to be involved in pain perception and analgesic responsiveness, and subjective outcomes. There were no significant associations for the opioid mu-receptor (OPRM1) and pain or QoL. However, the rs2236861 SNP in the opioid delta-receptor (OPRD1) showed nominally significant associations with worst pain (p=0.022), average pain (p=0.03) and pain interference (p=0.02) at baseline. The rs1045642 SNP in the ABCB1 drug transporter gene was nominally associated with worst pain (p=0.047) and average pain (p=0.019) after bortezomib-based induction therapy. A SNP rs13361160 in the chaperonin CCT5 gene was associated with worst pain (p=0.033), least pain (p=0.006) and pain interference (p=0.03). It was also associated with self-reported global QoL (P=0.014). Conclusions. We report the first PROs using self-reported QoL and pain assessments in myeloma patients having salvage ASCT or NTC. Global QoL was worse and side-effects of treatment higher after ASCT2 for up to 6 months post-randomisation but then equalised. Pain caused less interference with daily living after NTC but became more severe at 2 years, possibly associated with relapse. Patients who reported lower concerns about side-effects of treatment after ASCT2 had a significant TTP advantage. The genomic analyses suggest a potential inherited predisposition that influences both pain and quality of life and warrants further exploration. Disclosures Ahmedzai: Mundipharma: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; Grunenthal: Consultancy, Research Funding, Speakers Bureau. Snowden:Sanofi: Consultancy; MSD: Consultancy, Other: Educational support, Speakers Bureau; Janssen: Other: Educational support, Speakers Bureau; Celgene: Other: Educational support, Speakers Bureau. Williams:Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Cavenagh:Janssen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Parrish:Janssen: Speakers Bureau; Celgene: Speakers Bureau. Yong:Amgen: Honoraria; Novartis: Consultancy; Takeda: Honoraria; BMS: Honoraria; Janssen: Honoraria; Autolous: Consultancy. Cavet:Celgene: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau. Bird:Celgene: Speakers Bureau; Janssen: Other: Educational support; Amgen: Consultancy; Novartis: Consultancy; Pfizer: Consultancy. Ashcroft:Janssen: Consultancy, Other: Educational support. Brown:Bayer: Research Funding; Roche: Research Funding; Celgene: Research Funding; Janssen: Research Funding. Morris:Celgene: Other: Meeting support; Janssen: Other: Meeting support. Cook:Celgene: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy; Takeda Oncology: Consultancy, Research Funding, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau.
6
Chen, Zhan Fang, Xiao Ming Zhang, Qi Chang Chen, Teng Fei Ma, Huan Wang, and Xin Feng. "Design and Implementation of an Elementary School Online Registration and Enrollment Position Allocation System Based on Three-Tier Architecture." Applied Mechanics and Materials 373-375 (August 2013): 1843–48. http://dx.doi.org/10.4028/www.scientific.net/amm.373-375.1843.
Full textAbstract:
With extensive and thorough research on the three-tier B/S/D architecture and software development theory, we develop an elementary school online registration and allocation system using the bit-operation and template layered management technology in authorization management and implemented a three-tier management information system for Changchun city educational bureau, districts educational bureau to local elementary schools. In the allocation module, we propose an isometric random sample algorithm which is a fair and efficient allocation algorithm. Later, we discuss our in-depth analysis on the overall framework of the platform and each function module of the elementary school online registration and allocation system.
7
Burmester, G. R., J. M. Alvaro-Gracia, N. Betteridge, J. Calvo, B. Combe, P. Durez, R. J. O. Ferreira, et al. "THU0579 “EVOLVING THE MANAGEMENT OF RA” PROGRAMME: EDUCATIONAL TOOLS TO SUPPORT DAILY PRACTICE." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 531.1–531. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1219.
Full textAbstract:
Background:The eRA (evolving the management of RA) programme was initiated in Europe to provide practical educational tools that address unmet needs in the management of rheumatoid arthritis (RA). Several eRA tools – covering early access to care, management of comorbidities, treat-to-target strategies, and patient empowerment – are available to the rheumatology community. Through ongoing activities, the eRA Steering Committee (SC) identified a need for tools on non-pharmacological management of RA.Objectives:To improve accessibility to eRA tools for rheumatology professionals; to review the evidence base of non-pharmacological interventions to create new eRA resources that may support management decisions.Methods:A web platform providing information on eRA programme and tools was developed in 2019. The platform collects survey-based metrics to quantify perception of eRA and use of eRA tools in clinical practice. Platform and tools are translated to further support access and use across Europe.To address unmet needs in non-pharmacological patient management, the eRA SC reviewed the core literature on agreed priority interventions, including physical activity, diet, patient education and self-management, psychosocial interventions, occupational therapy and orthotics, hand exercises, and hydrotherapy/balneotherapy. Available evidence for each intervention was assessed and graded according to the Oxford Centre for Evidence-based Medicine Levels of Evidence.Results:The eRA web platform is now live in 3 countries (www.evolvingthemanagementofRA.com), hosting translated copies of the eRA tools, with additional countries launching throughout 2020.From a review of core literature on non-pharmacological interventions, the eRA SC determined that strong evidence exists to support use of physical activity, patient education and self-management, psychosocial interventions, and occupational therapy and orthotics. Evidence was lacking or conflicting for diet and nutrition, hand exercises, and balneotherapy/hydrotherapy. A set of educational slides was produced by the eRA SC to summarise the evidence (Fig. 1) and provide top-line guidance on use of interventions in practice that should engage relevant members of the multi-disciplinary team. These slides are available through eRA dissemination activities.Conclusion:The eRA programme content is now freely available to health care professionals in several countries on a web platform, supported by translations of the eRA tools. An additional slide set on non-pharmacological management serves to further increase the practical guidance of this programme’s educational offering.Acknowledgments:The eRA programme is funded by Sanofi Genzyme. Programme direction and content creation are driven by an independent Steering CommitteeDisclosure of Interests:Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Jose-Maria Alvaro-Gracia Grant/research support from: Abbvie, Elli-Lilly, MSD, Novartis, Pfizer, Consultant of: Abbvie, BMS, Janssen-Cilag, Elli-Lilly, MSD, Novartis, Pfizer, Sanofi, Tigenix, Roche, UCB, Paid instructor for: Elli-Lilly, Pfizer, Roche, Speakers bureau: Abbvie, BMS, Janssen-Cilag, Elli-Lilly, Gedeon Richter, MSD, Novartis, Pfizer, Sanofi, Tigenix, Roche, UCB, Neil Betteridge Consultant of: Amgen, Eli Lilly and Company, Grunenthal, GSK, Sanofi Genzyme, Jaime Calvo Grant/research support from: Lilly, UCB, Consultant of: Abbvie, Jansen, Celgene, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp & Dohme; Pfizer; Roche-Chugai; UCB, Patrick Durez Speakers bureau: AbbVie, Bristol-Myers Squibb, Celltrion, Eli Lilly, Pfizer, Sanofi, Ricardo J. O. Ferreira Grant/research support from: Abbvie, Consultant of: Sanofi Genzyme, Amgen, MSD, Paid instructor for: UCB, Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant of: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Medac MSD France, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi Aventis, SOBI and UCB, Annamaria Iagnocco Grant/research support from: Abbvie, MSD and Alfasigma, Consultant of: AbbVie, Abiogen, Alfasigma, Biogen, BMS, Celgene, Eli-Lilly, Janssen, MSD, Novartis, Sanofi and Sanofi Genzyme, Speakers bureau: AbbVie, Alfasigma, BMS, Eli-Lilly, Janssen, MSD, Novartis, Sanofi, Carlomaurizio Montecucco: None declared, Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Sofia Ramiro Grant/research support from: MSD, Consultant of: Abbvie, Lilly, Novartis, Sanofi Genzyme, Speakers bureau: Lilly, MSD, Novartis, Andrea Rubbert-Roth Consultant of: Abbvie, BMS, Chugai, Pfizer, Roche, Janssen, Lilly, Sanofi, Amgen, Novartis, Tanja Stamm Grant/research support from: AbbVie, Roche, Consultant of: AbbVie, Sanofi Genzyme, Speakers bureau: AbbVie, Roche, Sanofi, Zoltán Szekanecz Grant/research support from: Pfizer, UCB, Consultant of: Sanofi, MSD, Abbvie, Pfizer, Roche, Novertis, Lilly, Gedeon Richter, Amgen, Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Mart van de Laar Consultant of: Sanofi Genzyme, Speakers bureau: Sanofi Genzyme
8
Cook, Gordon, Cathy Williams, David A. Cairns, Anna Hockaday, Jamie Cavenagh, John A. Snowden, Christopher Parrish, et al. "A Salvage Autologous Stem Cell Transplant (ASCT2) Induces Superior Overall Survival Following Bortezomib-Containing Re-Induction Therapy for Relapsed Multiple Myeloma (MM): Results from the Myeloma X (Intensive) Trial." Blood 126, no. 23 (December 3, 2015): 394. http://dx.doi.org/10.1182/blood.v126.23.394.394.
Full textAbstract:
Abstract Introduction: Autologous transplantation (ASCT) in myeloma (MM) is standard consolidative therapy in first line therapy in eligible patients. We have shown definitely that a salvage ASCT in relapse setting can induce superior durability of responses (time-to-progression; TTP) over non-transplant consolidation with oral cyclophosphamide after a proteasome inhibitor-based re-induction schedule (ISRCTN601231201). The secondary end point of this multi-centre phase III randomised controlled trial was to evaluate the impact of salvage ASCT on the overall survival (OS_ of patients relapsing after a prior ASCT and delineate patient subgroups that may benefit the most. Patients and Methods: Eligible patients with MM relapsing after a prior ASCT were enrolled. All patients were re-induced with Bortezomib, Doxorubicin and Dexamethasone (PAD) therapy delivered in 2-4 21-day cycles before 1:1 randomization to either a second ASCT (melphalan 200mg/m2 iv; ASCT2 supported by either stored or remobilized stem cells) or low dose consolidation with weekly cyclophosphamide 400mg/m2 PO for 12 weeks (Non-Transplant Consolidation; NTC). Response was assessed (by IMWG criteria) after re-induction and 100 days post-randomization with TTP being determined as the primary end-point. Patients were stratified by β2microglobulin (β2M) at trial entry, ASCT1 TTP and response to re-induction, analyzed according to cytogenetic abnormalities by iFISH (unfavorable: t(4;14), t(14;16) and del17p) with OS was a key secondary endpoint. Results: 297 patients were entered into the study and 174 randomized from April 2008 to November 2012: ASCT2 n=89, NTC n=85. Median age was 61 (range 38-75) with 73.6% of patients relapsing more than 24 months from first ASCT. ORR to re-induction therapy was 79.4% with a 16.0% sCR/CR rate. Post-randomization, sCR/CR was significantly higher after ASCT2 (39.3% [95% CI 29.1,50.3] vs 22.4% [95% CI 14.0,32.7]; p=0á012). The median follow-up is 52 months (IQR range 41, 62) and the up-dated TTP demonstrates continued advantage in ASCT2 cohort compared to NTC (19 months [95% CI 16,26] vs 11 months [95% CI 9,12]; Log Rank p<0.0001). 75 patients (43.1%) have died since randomization, primarily from disease progression (59.4%). The median survival was 67 months (95% CI 55, °) in the ASCT2 cohort compared with 52 months (95% CI 42,60) in the NTC cohort (Log Rank p=0.022). Cox proportional hazards regression (adjusted for stratification factors including whether PBSC was remobilized) showed a reduced hazard of death in the ASCT2 group compared to NTC (HR=0.56, 95%CI [0.35, 0.90], p=0.0169). CR/sCR to re-induction therapy (HR 0.14, p=0.032), ASCT1 TTP > 24m (HR0.60, p=0.089), β2M level <3.5mg/L (HR 0.35, p=0.039) and the absence of high risk iFISH (HR 0.36, p=0.007) were associated with improved OS in favour of ASCT2 (Fig. 1A). To-date, following progression on protocol, 88.7% in the ASCT2 and 84% in the NTC cohorts have received 3rd line therapy, primarily consisting of a lenalidomide based combination (88.9% in the ASCT2 and 81% in the NTC cohorts). 20 patients (26.7%) in the NTC cohort underwent salvage ASCT in 3rd/4th line (NTC/ASCT2), with 1 patient in each cohorts proceeding to allogeneic SCT. The PFS2 was significantly better in the ASCT2 compared with both NTC/ASCT2 and NTC cohorts (ASCT2: 67m, [95%CI 52,°] vs NTC/ASCT2: 31m, [95%CI 23,42] vs NTC 39m, [95%CI 32,47]; p<0.0001). Consequently, the 4-year OS demonstrated a superiority of a salvage ASCT in second line over 3rd line or not (ASCT2: 69% [95%CI 58,79] vs NTC/ASCT2: 61% [95%CI 52,69] vs NTC 50% [95%CI 36,64]) where the OS in NTC groups split by 3rd line ASCT were not significantly different (p = 0.139, Fig. 1b). Conclusion: This long-term follow-up analysis demonstrates a clear advantage in terms of OS when salvage ASCT consolidates bortezomib-based re-induction therapy in patients with MM at first relapse. The delay of salvage ASCT to third line, though being suggestive of benefit over no salvage ASCT, does not confer the same degree of OS advantage as shown with a salvage transplant in second line. This data is key for patient-centered clinical decision-making. 1. G Cook, et al.. The Lancet Oncology, Vol. 15, No. 8, p874-885 Figure 1. Forest plots showing (a) heterogeneity of effect of randomised treatment on OS and (b) effect on OS of randomised treatment followed by ASCT at second relapse (NTC/ASCT2) Figure 1. Forest plots showing (a) heterogeneity of effect of randomised treatment on OS and (b) effect on OS of randomised treatment followed by ASCT at second relapse (NTC/ASCT2) Figure 1B. Figure 1B. Disclosures Cook: Amgen: Consultancy, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy; Sanofi: Consultancy, Speakers Bureau; Takeda Oncology: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau. Williams:Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. Cavenagh:Amgen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau. Snowden:MSD: Consultancy, Other: Educational support, Speakers Bureau; Janssen: Other: Educational support, Speakers Bureau; Celgene: Other: Educational support, Speakers Bureau; Sanofi: Consultancy. Parrish:Janssen: Speakers Bureau; Celgene: Speakers Bureau. Yong:Takeda: Honoraria; Autolous: Consultancy; Janssen: Honoraria; Novartis: Consultancy; BMS: Honoraria; Amgen: Honoraria. Cavet:Celgene: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau. Bird:Janssen: Other: Educational support; Celgene: Speakers Bureau; Amgen: Consultancy; Novartis: Consultancy; Pfizer: Consultancy. Heartin:Celgene: Speakers Bureau; Janssen: Consultancy. O'Connor:Celgene: Research Funding. Ashcroft:Janssen: Consultancy, Other: Educational support. Brown:Janssen: Research Funding; Roche: Research Funding; Celgene: Research Funding; Bayer: Research Funding. Morris:Janssen: Other: Meeting support; Celgene: Other: Meeting support.
9
Turner, J. Neville. "The Childrens Bureau of Australia." Children Australia 11, no. 4 (1986): 21. http://dx.doi.org/10.1017/s0312897000015782.
Full text
10
Dawkins, Monique D., Firas El Chaer, Leigh Boehmer, Ashkan Emadi, Elias Jabbour, Jeffrey Kendall, Barbara B. Rogers, Sandra Kurtin, Mohamed Hersi, and Meredith Barnhart. "Education and Promotion of MRD Testing within the Multidisciplinary Cancer Care Team for Adults with Acute Lymphoblastic Leukemia in the Community Setting." Blood 134, Supplement_1 (November 13, 2019): 5834. http://dx.doi.org/10.1182/blood-2019-123461.
Full textAbstract:
Background: The Association of Community Cancer Centers (ACCC) is an education and advocacy organization with a diverse membership, representing all cancer program types with the largest majority (75%) being community-based cancer programs and private practices. Beyond the academic setting, ACCC seeks to expand education on the advancements in all cancer care and since measurable residual disease (MRD) is the most important prognostic factor that guides the therapy for patients with acute lymphoblastic leukemia (ALL), this project aimed to emphasize the importance of MRD testing for adult patients with ALL in the community oncology setting. Objective: The ACCC led a national initiative, in partnership with the Leukemia & Lymphoma Society (LLS), to improve the diagnosis, treatment and management of adult patients diagnosed with ALL in community oncology practices. This educational program focused on understanding the benefits of knowing patients' MRD testing and interpretation and the need to integrate this testing into standard of care practice in community oncology practice settings. Methods: This one-year programmatic initiative was designed by a group of multidisciplinary oncology faculty and structured around a peer-to-peer learning format that enabled ALL expert faculty to share effective practices for the treatment, care coordination and management of adult patients with ALL. An environmental scan was conducted to understand the landscape for utilization of MRD data in the community setting. Challenges and barriers identified in six key areas ((Initial Diagnostic Workup, Shared Decision Making, MRD Testing, Patient Access, Cost, and Reimbursement, Side-effect Management and Transitions in Care) were addressed by the development of healthcare professional-focused educational tools. Results: The educational material developed as part of the program include an environmental scan, blog series and webinar series that was viewed over 300 times by engaged ACCC members representing more than 75 cancer programs across 27 states. The four-part blog series covered a pathologist's perspective on the importance of MRD testing, a pharmacist's views on incorporating health literacy for patients, and social work and nursing perspectives on challenges with helping adult patients manage an ALL diagnosis. The three-part webinar series included an informative ASH 2018 update that included key abstracts and findings, a webinar that included a patient and care providers which shed light on the support needed along a patient's journey, and a webinar that explored critical insights for treating adult ALL from the perspective of a pharmacist, pathologist and oncologist. These enduring resources are available on-demand for the multidisciplinary care team. Conclusions: This program demonstrated the success of adopting a peer-to-peer educational learning platform to educate the multidisciplinary team providing care for adult patients diagnosed with ALL. Given rapid technological advances and emerging indications, the comprehensive educational materials developed were useful for the education of both the treating team and the patients in the community oncology setting. Disclosures Emadi: Jazz Pharmaceuticals: Research Funding; NewLink Genetics: Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; KinaRx: Membership on an entity's Board of Directors or advisory committees, Other: Co-Founder and Scientific Advisor, Patents & Royalties; Genentech: Consultancy, Honoraria. Jabbour:Takeda: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Cyclacel LTD: Research Funding. Kendall:Eli Lilly: Speakers Bureau; Novartis: Speakers Bureau; Pfizer: Speakers Bureau. Rogers:Teva: Speakers Bureau; Takeda: Honoraria; Genentech: Speakers Bureau; Seattle Genetics: Speakers Bureau; Abbvie: Speakers Bureau; Cardinal Health: Honoraria; Genentech: Honoraria; Mylan: Honoraria; Coherus: Speakers Bureau.
11
Ashcroft, John, David A. Cairns, Cathy Williams, A. Hockaday, J. D. Cavenagh, John A. Snowden, Christopher Parrish, et al. "Outcomes Following Salvage Autologous Stem Cell Transplant (ASCT2) Vs Low Dose Alkylating Consolidation Therapy Following Bortezomib-Containing Re-Induction for Relapsed Multiple Myeloma (MM) May be Dependent on Age and Symptomatic Status Initiation of Re-Induction: Results from the Myeloma X (Intensive) Trial." Blood 126, no. 23 (December 3, 2015): 1981. http://dx.doi.org/10.1182/blood.v126.23.1981.1981.
Full textAbstract:
Abstract Introduction: The impact of biological variables on treatment outcomes for patients with multiple myeloma (MM) are key to a stratified medicine approach. Whether to re-start therapy at relapse on serological vs symptomatic progression is an important clinical question. Though salvage autologous transplantation (ASCT2) in MM has been shown to induce superior durability of responses over low-dose alkylating consolidation therapy in the relapsed setting (ISRCTN601231201), who benefits most from this strategy remains to be defined. An important subgroup comparison in Myeloma X was to evaluate the impact of age & disease stage on outcomes after ASCT2 vs non-transplant consolidation (NTC). Patients and Methods: Eligible patients with MM relapsing after prior ASCT were enrolled. All patients received Bortezomib, Doxorubicin & Dexamethasone (PAD) prior to 1:1 randomization between ASCT2 or NTC with weekly cyclophosphamide for 12 weeks. Response was assessed (by IMWG criteria) after re-induction & 100 days post-randomization. Patients were stratified by β2M at trial entry & ASCT1 time-to-progression (TTP). The 10 endpoint was TTP. Overall survival (OS) was a key 20 endpoint with subgroup analysis of stage, age, symptomatic status & cytogenetic risk. Results: 297 patients were entered & 174 randomized: ASCT2 n=89, NTC n=85. Median age was 61 (range 38-75) with 22% of patients >65 years. The median TTP from ASCT1 was 31 months (range 8-149) with no impact in terms of age at trial entry. 43% of patients were deemed to have symptomatic relapse (sRel) at trial entry based on CRAB criteria (anaemia 30%, renal disease 16% and hypercalcaemia 5%). There was no significant difference in the median ASCT1 TTP between trial entrants with sRel compared to asymptomatic relapse (aRel: 35 months [95%CI 32,38] vs sRel: 36 months [95%CI 32,40]; Mann-Whitney p=0.657). Post-randomization, sCR/CR rate was significantly higher after ASCT2 (odds ratio (OR) = 0.42 [95%CI 0.21,0.85]; p=0á012), with no significant age effect identified (likelihood ratio test (LRT) p=0.131). The impact of aRel compared to SRel demonstrated a non-significant trend towards benefit in sCR/CR rate for aRel patients (aRel: OR=0.28 [95%CI 0.11,0.76] vs sRel: OR=0.66 [95%CI 0.23,1.93]; LRT p=0.343). The median follow-up is 52 months (IQR 41, 62) & updated TTP demonstrates continued advantage of ASCT2 over NTC (hazard ratio (HR)=0.45 [95%CI 0.31,0.64]; p<0.0001). Age was not found to have an independent impact on TTP. However, when the impact of aRel was compared with sRel, a non-significant trend towards benefit was demonstrable (aRel: HR=0.34 [95%CI 0.21,0.57]; sRel: HR=0.52 [95%CI 0.30,0.89]; LRT p=0.082) (Fig 1a). Following progression, 88.7% in the ASCT2 and 84.0% in the NTC cohorts have received 3rd line therapy (primarily lenalidomide-based). The impact of both age at trial entry (²65 yrs: HR=0.36 [95%CI 0.22,0.58]; >65 yrs: HR=1.02 [95%CI 0.30,3.52]; LRT p=0.827) & symptomatic status (aRel: HR=0.34 [95%CI 0.18,0.64]; sRel: HR=0.36 [95%CI 0.18,0.71]; LRT p=0.697) on PFS2 showed non-significant trends towards benefit. In particular, older patients appearing to derive less benefit from ASCT2 in terms of PFS2. When OS by randomized treatment is considered in relation to age (²65 yrs: HR=0.53 [95%CI 0.32,0.90]; >65 yrs: HR=2.34 [95%CI 0.59,9.35]; LRT p=0.635) & symptomatic status (aRel: HR=0.44 [95%CI 0.22,0.90]; sRel: HR=0.68 [95%CI 0.34,1.36]; LRT p=0.347) non-significant trends towards further benefit can be observed (Fig 1b), reflected by the 4-year survival (ASCT2 - aRel: 75.5% vs sRel: 60.2%; logrank p=0.080 & NTC - aRel: 55.1% vs sRel: 49.0; logrank p=0.707) & age at trial entry (ASCT2 - ²65 yrs: 71.2% vs >65 yrs: 58.9; logrank p=0.726 & NTC - ²65 yrs: 47.9% vs >65 yrs: 68.2; logrank p=0.653). Conclusion: These results show both a clear OS advantage to ASCT2 post bortezomib based re-induction therapy & that this advantage may well be improved in younger patients with biochemical, rather than symptomatic relapse. This data is key for patient-centered clinical decision-making & adds to previous analysis demonstrating a clear advantage to ASCT2 in terms of TTP and PFS in patients with MM at first relapse1. 1. G Cook, et al. The Lancet Oncology, Vol. 15, No. 8, p874-885. Figure 1. Forest plot showing impact of age & symptomatic status at retreatment on (a) TTP and (b) OS of randomised treatment. To the left favors ASCT2 and to the right NTC. (a) TTP (b) OS Figure 1. Forest plot showing impact of age & symptomatic status at retreatment on (a) TTP and (b) OS of randomised treatment. To the left favors ASCT2 and to the right NTC. / (a) TTP. / (b) OS Disclosures Ashcroft: janssen: Consultancy, Research Funding; celgene: Consultancy, Honoraria; amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Williams:Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Cavenagh:janssen: Consultancy, Speakers Bureau; novartis: Consultancy, Speakers Bureau; celgene: Consultancy, Speakers Bureau; amgen: Consultancy, Speakers Bureau. Snowden:Sanofi: Consultancy; MSD: Consultancy, Other: Educational support, Speakers Bureau; Janssen: Other: Educational support, Speakers Bureau; Celgene: Other: Educational support, Speakers Bureau. Parrish:Celgene: Speakers Bureau; Janssen: Speakers Bureau. Yong:Janssen: Honoraria; BMS: Honoraria; Takeda: Honoraria; Novartis: Consultancy; Autolous: Consultancy; Amgen: Honoraria. Cavet:Celgene: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau. Bird:Pfizer: Consultancy; Novartis: Consultancy; Amgen: Consultancy; Celgene: Speakers Bureau; Janssen: Other: Educational support. Heartin:Janssen: Consultancy; Celgene: Speakers Bureau. O'Connor:Celgene: Research Funding. Brown:Janssen: Research Funding; Celgene: Research Funding; Roche: Research Funding; Bayer: Research Funding. Morris:Celgene: Other: Meeting support; Janssen: Other: Meeting support. Cook:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Chugai: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Jazz Pharma: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria, Speakers Bureau.
12
Peyvandi, Flora, Pier Mannuccio Mannucci, Isabella Garagiola, Mohsen Elalfy, Amal El-Beshlawy, Madatha V. Ramanan, Peyman Eshghi, et al. "Source of Factor VIII Replacement (PLASMATIC OR RECOMBINANT) and Incidence of Inhibitory Alloantibodies in Previously Untreated Patients with Severe Hemophilia a: The Multicenter Randomized Sippet Study." Blood 126, no. 23 (December 3, 2015): 5. http://dx.doi.org/10.1182/blood.v126.23.5.5.
Full textAbstract:
Abstract Background We conducted an investigator-driven, multicenter, open label, randomized study to establish whether the source of factor VIII (FVIII) replacement (plasma-derived, pd; or recombinant, r) affects the rate of inhibitory alloantibodies in previously untreated patients (PUPs) with severe hemophilia A. Methods Between 2010 and 2014, 303 PUPs who provided consent through their tutors were screened at 42 participating sites in 14 countries from Africa, the Americas, Asia and Europe. The original aim was to screen 300 patients, randomize 270 (10% screening failure) and follow them for 50 exposure days (ED) or 3 years. Once the intended numbers were included, follow-up was terminated due to logistic and budgetary reasons. Screening criteria were age <6 yrs, plasma FVIII activity <1%, no previous treatment with FVIII concentrates, minimal exposure (less than 5 times) to blood components. Eligible patients were 1:1 block-randomized to a FVIII source class and exclusively treated with a single pd- or rFVIII product, that within each class was allocated on the basis of site licensing and availability. Patients were monitored for inhibitor onset at pre-established and frequent time intervals. Primary outcome was any FVIII inhibitor at titres ≥0.4 BU/ml as assayed centrally. High-titred inhibitors (peak levels >5 BU/ml) were a secondary outcome. Patients were censored at the end of the follow-up (50 EDs, 3 years or study end), at inhibitor development or drop-out. Kaplan-Meier and Cox regression survival analyses took into account as putative confounders FVIII gene mutations, ethnicity, hemophilia and inhibitor family history, previous blood component exposure, therapeutic regimen, age at first treatment and country site. Results Of 303 screened patients, 39 were screening failures, and 13 were excluded because 3 patients had received >5 treatments with blood components and 10 were not infused after randomization. The remaining 251 patients were analysed and 35 had truncated follow-up (25 dropout, 10 study termination). Patients were aged 0-81 months at randomization (median 14 months) and received between 1 and 50 infusions of FVIII concentrates (median 22). Of those who did not develop an inhibitor, over 70% had >20 ED. 76 patients developed an inhibitor, of which 50 were high-titred. The cumulative inhibitor incidence was 35.4% (95% confidence interval (CI95) 28.9-41.9%). 90% of inhibitors developed within 20 EDs, both for all and high-titre inhibitors. After randomization 125 patients received pdFVIII and 126 rFVIII. The putative confounders were equally divided between the two product class arms. There were 29 inhibitors (20 high-titred) in the group treated with the class of pdFVIII and 47 (30 high-titred) in those treated with rFVIII. The cumulative inhibitor incidence was 26.7% (CI95 18.3-35.1%) for pdFVIII and 44.5% (CI95 34.7-54.3%) for rFVIII (Figure). For high-titre inhibitors the cumulative incidence was 18.5% (CI95 12.1-26.9%) for pdFVIII and 28.4% (CI95 19.6-37.2%) for rFVIII. By univariate Cox regression analysis rFVIII was associated with an 87% higher incidence of inhibitors than pdFVIII (hazard ratio (HR) 1.87, CI95 1.18-2.97). For high-titre inhibitors the rate was 70% increased (HR 1.70, CI95 0.96-2.99). The associations did not materially change after adjustment for putative confounders: in adjusted models the rate remained 70-90% elevated for rFVIII vs pdFVIII. When analysis was restricted to sites that had not randomized patients to a second generation full length rFVIII or pdFVIII (n=131 patients, 25 inhibitors), the risk of other rFVIII concentrates vs pdFVIII was still twofold increased (HR 1.99, CI95 1.00-3.99). Conclusions The rFVIII product class was associated with a 1.87-fold higher incidence of inhibitors than the pdFVIII class. This difference remained even when second generation full length rFVIII concentrate was excluded from the analyses. The results of this randomized study have implications in the choice of product for management of PUPs, as inhibitor development remains a major challenge in the management of haemophilia A. (Funded by the Angelo Bianchi Bonomi Foundation, Italian Ministry of Health, Grifols, Kedrion and LFB - Registed at EudraCT 2009-001186-88). Figure 1. Figure 1. Disclosures Peyvandi: Octapharma: Other: Investigator; LFB, Kedrion, Novonordisk, Bayer, Roche, CSL Behring.: Consultancy, Honoraria, Research Funding. Mannucci:Novonordisk, Grifols, Kedrion, Bayer, Biotest, Baxalta: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Karimi:Octapharma: Other: Investigator. Young:Baxter, Grifols: Consultancy, Honoraria. Santagostino:Roche: Speakers Bureau; Bayer: Speakers Bureau; Baxter/Baxalta: Speakers Bureau; Octapharma: Speakers Bureau; Biotest: Speakers Bureau; Novo Nordisk: Speakers Bureau; Kedrion: Speakers Bureau; Biogen/Sobi: Speakers Bureau; CSL Behring: Speakers Bureau; Pfizer: Research Funding, Speakers Bureau. Mancuso:Baxter, Pfizer, CSL Behring, Baxter, Sobi/Biotest: Consultancy; Novo Nordisk, Bayer: Speakers Bureau. Mahlangu:Biogen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring: Research Funding; NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biotest: Honoraria, Membership on an entity's Board of Directors or advisory committees. Bonanad:Baxalta: Research Funding. Ewing:Baxter, Novo Nordisk, Grifols, Bayer, Kedrion: Honoraria. Owaidah:King abdulaziz city for science, Novo Nordisk, Bayer: Honoraria, Research Funding. Kobrinsky:Octapharma: Speakers Bureau; CSL Behring: Speakers Bureau; Sanofi: Speakers Bureau; Kedrion Biopharma: Membership on an entity's Board of Directors or advisory committees. Kavakli:Baxter: Other: advisory board member and received educational and investigational support; Bayer: Other: advisory board member and received educational and investigational support; Novo Nordisk: Other: advisory board member and received educational and investigational support; Pfizer: Other: advisory board member and received educational and investigational support; Bio Products Laboratory: Other: received educational and investigational support; CSL Behring: Other: received educational and investigational support; Octapharma: Other: received educational and investigational support. Manco-Johnson:Baxter, bayer, biogen, CSL Behring, NovoNordish: Honoraria. Neme:Novo Nordisk and Pfizer: Other: fees for speaking. Wicklund:NovoNordisk, Bayer, Baxter (now Baxalta), Biogen-Idec, CSL-Behring, National Hemophilia Foundation: Honoraria, Membership on an entity's Board of Directors or advisory committees. Zulfikar:Eczacýbaþý-Baxter, Pfizer, Novo Nordisk: Consultancy, Honoraria, Research Funding.
13
Zinzani, Pier Luigi, Vladimir Melnichenko, Krimo Bouabdallah, Jan Walewski, Alejandro Majlis, Laura Fogliatto, Dolores Caballero, et al. "Pembrolizumab Monotherapy in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma (PMBCL): 3-Year Follow-up of the Keynote-170 Study." Blood 136, Supplement 1 (November 5, 2020): 42–43. http://dx.doi.org/10.1182/blood-2020-137080.
Full textAbstract:
Introduction: No standard of care exists for patients (pts) with relapsed or refractory primary mediastinal B-cell lymphoma (rrPMBCL). As such, pts typically receive therapies recommended for diffuse large B-cell lymphoma, with poor prognosis. Similar to classical Hodgkin lymphoma, rrPMBCL tumors often overexpress the programmed death 1 (PD-1) ligands, PD-L1 and PD-L2. Data from the first full analysis of the phase 2 KEYNOTE (KN)-170 (NCT02576990) study showed that pembrolizumab provided effective and durable antitumor activity with a manageable safety profile in patients with rrPMBCL. These data led to the FDA approval of pembrolizumab for pts with rrPMBCL after ≥2 prior therapies. In this aggressive malignancy with few salvage options, duration of remission with PD-1 blockade remains a critical question. Here we present data from KN170 with an additional 24 months of follow-up in patients with rrPMBCL. Methods: Pts with rrPMBCL who had relapsed after or were ineligible for autologous stem cell transplant with ≥2 lines of prior therapy were enrolled in KN170 to receive 200 mg pembrolizumab IV Q3W until disease progression or toxicity, for up to 2 years. Tumor response was assessed Q12W with PET/CT scans by IWG 2007 criteria. The primary endpoint was objective response rate (ORR) by blinded independent central review (BICR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Exploratory endpoints included response by Lugano 2014 criteria. The data cutoff date for this analysis was May 7, 2020. Results: At the data cutoff date, among all treated pts (N=53), 13 had completed 2 years of treatment and 40 had discontinued largely due to progression (n=30). The ORR was 45% (24/53; 95% CI 32-60) with a CR rate of 19% (10/53; 13/53 [25%] by Lugano criteria). No patient who achieved CR by BICR had received consolidation therapy or had progressed at data cutoff. After a median study follow-up of 43.1 months (range, 35.6-50.7) the median DOR was not reached (range, 1.1+ to 46.9+ mo); 76% of pts had a response duration ≥36 mo. Median PFS was 5.5 mo (95% CI, 2.7-15.1), with 36-mo PFS rate of 34%. The median OS was 22.3 mo (95% CI, 7.3 to not reached) with 36-mo OS rate of 45%. At data cutoff, 50 (94%) pts had at least one adverse event (AE), with 30 (57%) having a treatment-related AE. The most common treatment-related AEs were neutropenia (19%), asthenia (9%), hypothyroidism (8%), fatigue (6%), and pyrexia (6%). Grade ≥3 treatment-related AEs occurred in 12 (23%) pts. Six (11%) pts had an immune-mediated AE. There were no treatment-related grade 5 events. Conclusion: Results from the longer-term follow-up of KN170, the largest prospective clinical trial in rrPMBCL, shows that pembrolizumab provides robust and durable antitumor activity with a manageable safety profile in patients with rrPMBCL. Disclosures Zinzani: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics, Inc.: Honoraria, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bouabdallah:Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria. Walewski:Roche: Consultancy, Honoraria, Other: travel expenses, Research Funding; GSK/Novartis: Research Funding; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy. Caballero:Gilead: Other: travel; Roche: Other: travel; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: travel; Kite: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: travel; BMS: Other: travel. Christian:Acerta: Research Funding; Celgene: Research Funding; Genentech: Research Funding; Merck: Research Funding; Millenium: Research Funding; MorphoSys: Research Funding; F Hoffman-La Roche: Research Funding; Triphase: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees; AstraZenica: Membership on an entity's Board of Directors or advisory committees. Özcan:Takeda: Honoraria, Other: travel, Research Funding; Roche: Other: travel, Research Funding; Bayer: Research Funding; Abbvie: Other: travel, Research Funding; Archigen: Research Funding; Celgene: Research Funding; MSD: Research Funding; Novartis: Research Funding; Amgen: Honoraria, Other: travel; BMS: Other; Jazz: Other; Sanofi: Other; Abdi Ibrahim: Other; Janssen: Other: travel, Research Funding. Salles:Bristol Myers Squibb: Consultancy, Other; Takeda: Consultancy, Honoraria, Other; Gilead: Consultancy, Honoraria, Other: Participation in educational events; Debiopharm: Consultancy; Kite: Consultancy, Honoraria, Other; MorphoSys: Consultancy, Honoraria, Other; Janssen: Consultancy, Honoraria, Other: Participation in educational events; Novartis: Consultancy, Honoraria, Other; F. Hoffman-La Roche Ltd: Consultancy, Honoraria, Other; Celgene: Consultancy, Honoraria, Other: Participation in educational events; Epizyme: Consultancy; Karyopharm: Consultancy; Autolus: Consultancy; Amgen: Honoraria, Other: Participation in educational events; Abbvie: Consultancy, Honoraria, Other: Participation in educational events; Genmab: Consultancy. Shipp:Celgene: Honoraria; Ono Pharmaceutical: Honoraria; Bayer: Honoraria; Bristol Myers Squibb: Consultancy, Research Funding; Merck: Research Funding. Thompson:Merck Sharp & Dohme Corp.: Current Employment. Orlowski:Merck Sharp & Dohme Corp.: Current Employment. Marinello:Merck & Co., Inc., Kenilworth, NJ, USA: Other: Stock ownership; Merck & Co., Inc.: Other: Travel, accommodations, expenses; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA: Current Employment. Armand:Pfizer: Consultancy; Merck & Co., Inc.: Consultancy, Honoraria, Research Funding; Adaptive: Consultancy, Research Funding; Affimed: Consultancy, Research Funding; Sigma Tau: Research Funding; Celgene: Consultancy; IGM: Research Funding; Otsuka: Research Funding; Tensha: Research Funding; Genentech: Research Funding; Infinity: Consultancy; ADC Therapeutics: Consultancy; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Roche: Research Funding.
14
Lindenmeyer, Kriste. "The U.S. Children's Bureau and Infant Mortality in the Progressive Era." Journal of Education 177, no. 3 (October 1995): 57–69. http://dx.doi.org/10.1177/002205749517700305.
Full textAbstract:
Early in the twentieth century, a growing child welfare movement led to the establishment of the first federal agency in the world, the U.S. Children's Bureau, designated to investigate and report on the circumstances of children. Appointed in 1912, the agency's first director, Julia Lathrop, focused on infant mortality, beginning with a year's study in Johnstown, Pennsylvania. The work stimulated a national effort to “save babies.” The Bureau's efforts led to the Sheppard-Towner Act of 1921, which funded educational and diagnostic work to lower the nation's high infant mortality rate. But this type of effort was short-lived. The article describes the course of the agency's work in the Progressive Era and evaluates its effect on current child welfare policy, a key area in the ongoing controversy over “welfare reform” and the role of the federal government in the provision of human services.
15
사노 미치오. "History Education by the Educational Affairs Bureau The Colonial Japanese Government in Korea in 1910s." JOURNAL OF KOREAN INDEPENDENCE MOVEMENT STUDIES ll, no. 38 (April 2011): 351–97. http://dx.doi.org/10.15799/kimos.2011..38.009.
Full text
16
Paul, Sujan Chandra, Md Arif Hosen, Jyotirmay Biswas, and Shahadat Hossain. "Primary education and its impact on literacy rate: A division wise comparative study of Bangladesh." International Journal of Research in Business and Social Science (2147- 4478) 10, no. 4 (June 14, 2021): 391–405. http://dx.doi.org/10.20525/ijrbs.v10i4.1186.
Full textAbstract:
This study investigates the impact of a number of educational institutions and students per teacher on the literacy rate. Data of 489 Upazilasrelating to the dependent (literacy rate) and independent variables (no. of educational institutions and students per teacher of different types of primary and equivalent educational institutions) of 8 Divisions were collected from District Statistics 2011 of Bangladesh Bureau of Statistics. The Ordinary Least Square (OLS) method is used in this study. This research found that a number of government primary schools had a significant positive relationship with the literacy rate in Barishal, Chittagong, Khulna, and Mymensingh Divisions.
17
Roaux, Cécile. "Le « bureau du directeur » : contribution à une approche ethnographique du pouvoir en école primaire." Les Sciences de l'éducation - Pour l'Ère nouvelle 53, no. 1 (2020): 97. http://dx.doi.org/10.3917/lsdle.531.0097.
Full text
18
Boss, Peter. "“The Childrens Bureau — The Next Thousand Years”." Children Australia 11, no. 2-3 (1987): 20–21. http://dx.doi.org/10.1017/s0312897000016787.
Full text
19
Coppens, Michiel, Lizhen Xu, Roisin Bavalia, Saskia Middeldorp, Peter Verhamme, John W. Eikelboom, Mark Crowther, et al. "Effects of Andexanet Alfa on Thrombin Generation in Bleeding Associated with Factor Xa Inhibitors." Blood 134, Supplement_1 (November 13, 2019): 711. http://dx.doi.org/10.1182/blood-2019-124596.
Full textAbstract:
Introduction Andexanet alfa is a modified recombinant inactive form of human factor Xa developed for reversal of factor Xa inhibitors. In the ANNEXA-4 study, patients with acute major bleeding within 18 h after administration of a factor Xa inhibitor were enrolled and received a bolus of andexanet, followed by a 2-h infusion (Connolly, NEJM 2019;380:1326). In this study, 82% of patients achieved effective hemostasis at 12 h and 10% developed a thrombotic event within 30 days. Anti-Xa activity decreased by 92% after the andexanet bolus but partially recovered after the end of the 2 h infusion. In the present analysis, we evaluated the effect of andexanet alfa on thrombin generation (TG) in patients enrolled in the ANNEXA-4 study and we explored whether TG predicts effective hemostasis or thrombotic events. Methods We included all patients who received andexanet alfa. TG was expressed as the endogenous thrombin potential (ETP) which is the area under the thrombin generation curve. We plotted mean TG at different timepoints between baseline and 30 days after andexanet alfa in patients treated with apixaban and rivaroxaban. We compared the absolute ETP level at 8 h (ETP-8H) after andexanet bolus as this was the first timepoint after the 2 h infusion for which an ETP level was available for most patients. We compared ETP-8H levels between patients with and without effective hemostasis and between those with and without thrombotic events, respectively. ETP-8H was evaluated as a predictor of effective hemostasis and thrombotic events by logistic regression analysis in all patients, and in subgroups of patients with intracranial hemorrhage (ICH) and non-ICH separately. In the ICH subgroups, ETP-8H was also evaluated as a predictor of absolute change in hematoma volume. Results The study population comprised 352 patients (mean age 77.4 years; 47% female) with acute major bleeding (64% ICH, 26% gastrointestinal, 10% other) treated with apixaban (55%), rivaroxaban (36%), enoxaparin (6%), or edoxaban (3%). ETP-8H was available for 327 patients (93%). In patients treated with apixaban or rivaroxaban, andexanet bolus promptly increased mean ETP and this was maintained during infusion. After end of infusion ETP fell but remained in the reference range for at least 18 hours (Figure 1). ETP-8H was similar in patients with or without effective hemostasis (Fig 2a, p = 0.544) and in patients with or without thrombotic complications (Fig 2b, p = 0.610). In the logistic regression analysis, ETP-8H did not predict effective hemostasis (p=0.491) or thrombotic events (p=0.743) (Table), and these results were consistent in ICH and non-ICH patients. ETP-8H did not predict hematoma growth in patients with ICH (p = 0.349). Conclusion A bolus of andexanet alfa, followed by a 2-h infusion in patients with factor Xa inhibitor associated major bleeding promptly restores thrombin generation and this effect is sustained for at least 18 hours. Thrombin generation at 8 h after andexanet bolus did not predict effective hemostasis, intracranial hematoma growth, or thrombotic events. This may be explained by the andexanet dose which was chosen to ensure full reversal of the factor Xa inhibitor in all patients. Disclosures Coppens: Bayer: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Daiichi Sankyo: Honoraria, Research Funding; Sanquin Blood Supply: Research Funding; Pfizer: Honoraria; Uniqure: Research Funding; CSL Behring: Honoraria, Research Funding; Portola Pharmaceuticals, Inc: Honoraria; Boehringer Ingelheim: Research Funding. Middeldorp:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Other: honoraria for advisory activities; Aspen: Research Funding; Portola Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: honoraria for advisory activities; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees, Other: honoraria for advisory activities; Bayer: Membership on an entity's Board of Directors or advisory committees, Other: honoraria for advisory activities, Research Funding; Sanofi: Speakers Bureau; Daiichi Sankyo: Other: honoraria for advisory activities, Research Funding. Verhamme:Portola Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer Healthcare: Consultancy, Research Funding, Speakers Bureau; Boehringer Ingelheim: Consultancy, Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding, Speakers Bureau; Leo Pharma: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy. Eikelboom:Heart and Stroke Foundation: Research Funding; Sanofi Aventis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Glaxo Smith Kline: Honoraria, Research Funding; Eli Lilly: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; Bayer: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding. Crowther:Bayer: Other: Data and Safety Monitoring Board, Research Funding, Speakers Bureau; BMS Canada: Membership on an entity's Board of Directors or advisory committees, Research Funding; Servier Canada: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Other: preparing educational material and/or providing educational presentations; CSL Behring: Other: preparing educational material and/or providing educational presentations; Diagnostica Stago: Other: preparing educational material and/or providing educational presentations, Research Funding; Alnylam: Equity Ownership; Asahi Kasei: Membership on an entity's Board of Directors or advisory committees; Alexion: Speakers Bureau; Shionogi: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees. Lu:Portola Pharmaceuticals: Employment, Equity Ownership. Yue:Portola Pharmaceuticals: Employment, Equity Ownership. Conley:Portola Pharmaceuticals, Inc.: Employment, Equity Ownership. Connolly:Portola Pharmaceuticals: Consultancy, Research Funding; Bayer Healthcare: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding.
20
Strapp, Chehalis M., Danica J. Drapela, Cierra I. Henderson, Emily Nasciemento, and Lauren J. Roscoe. "Psychology Students’ Expectations Regarding Educational Requirements and Salary for Desired Careers." Teaching of Psychology 45, no. 1 (December 15, 2017): 6–13. http://dx.doi.org/10.1177/0098628317744943.
Full textAbstract:
This study investigated the accuracy of psychology majors’ expectations regarding careers. Psychology majors, including 101 women and 35 men ( Mage = 23 years; standard deviationage = 6.25), indicated a desired career and estimated the level of education needed and the expected annual salary for the career. Students’ expectations were compared with Bureau of Labor Statistics data. Students completed the Career Decision-Making Self-Efficacy Scale Short Form to assess the career efficacy and expectations. Students overestimated education needed for a career, but salary estimates did not differ from market statistics. Students’ confidence in career choice and expected income was related to career efficacy. Results highlight the importance of career advising and support for psychology students entering the job market.
21
Alem Maulana Wulida Finnahar and Riya Fatmawati. "SISTEM KLASIFIKASI ARSIP DI BIRO AKADEMIK DAN KEMAHASISWAAN UNIVERSITAS NEGERI PADANG." Jurnal Pustaka Budaya 8, no. 1 (January 2, 2021): 31–47. http://dx.doi.org/10.31849/pb.v8i1.5632.
Full textAbstract:
This paper contains a discussion of how to use the archive classification system at the Bureau of Academic and Student Affairs, State University of Padang. The use of this archive classification system aims to assist employees at the Bureau of Academic and Student Affairs, State University of Padang in using the archive classification system according to their respective work units. The research method used in writing this paper is a qualitative descriptive research method. Data collection techniques were carried out by means of observation and interviews. The subject of data collection through observation at the Bureau of Academic and Student Affairs, State University of Padang. Observations are made by looking at how employees understand the classification of records. Furthermore, interviews were conducted with employees at the Bureau of Academic and Student Affairs, Padang State University. The author conducted a question and answer session with employees directly regarding the use of archive classification codes, the obstacles faced in using classification codes, and solutions to these problems. Based on these results, it can be concluded that the archive classification system in the Bureau of Academic and Student Affairs at the State University of Padang is actually used to assist employees in providing proper and correct archive classification codes. In the manual for the archive classification code at the Bureau of Academic and Student Affairs, State University of Padang, it can be concluded that the paper on the archive classification system at the Bureau of Academic and Student Affairs, State University of Padang is: (1) The archive classification system at the Bureau of Academic and Student Affairs, State University of Padang uses the subject system /problem (2) The archive classification system according to the Ministry of Research, Technology and Higher Education Regulation Number 23 of 2018 concerning Archive Classification, Archive Retention Schedule, and Security Classification System and Dynamic Archive Access in the academic and student fields has 6 archive classification codes, namely AK (academic) , TM (Student Admission), KR (Curriculum), EP (Educational Evaluation), Scholarship (BW), Student Affairs (KM).
22
KUSUMAYANTI, NI LUH ARDILA, I. KOMANG GDE SUKARSA, TJOKORDA BAGUS OKA, and I. PUTU EKA N. KENCANA. "KAJIAN TERHADAP TINGKAT PEMERATAAN PENDIDIKAN MENGGUNAKAN ANALISIS BIPLOT KLASIK DAN BIPLOT KEKAR." E-Jurnal Matematika 4, no. 2 (May 30, 2015): 37. http://dx.doi.org/10.24843/mtk.2015.v04.i02.p086.
Full textAbstract:
The aim of this research is to find the better from classical and robust biplot in determine dominant indicators of educational equity in Bali, NTB and NTT Provinces. This research based on secondary data obtain from Central Bureau of Statistics for year 2012/2013. Educational equity was portraited by Classical and Robust Biplot. The results of this research showed Robust Biplot is better method which goodness of fit is 90,64% meanwhile Classical Biplot as much as 83,62%. The Robust Biplot showed Students- Junior or Islamic Middle School Ratio and Students-Senior or Islamic High School were dominant indicators to educational equity in Bali, NTB and NTT Provinces.
23
Jackson, Edward, Piyali Chatterjee, Susan Smith, Karen Badal, and David E. Griffith. "1330. Diagnosis and Management of NTM Lung Disease: Effect of Online Educational Interventions on Infectious Disease Specialist Knowledge." Open Forum Infectious Diseases 5, suppl_1 (November 2018): S406. http://dx.doi.org/10.1093/ofid/ofy210.1163.
Full textAbstract:
Abstract Background Diagnosis and management of nontuberculous mycobacterial (NTM) lung disease is challenging for clinicians due to its rarity and the need for complicated, multidrug antibiotic regimens. The objective of this study was to determine whether online educational interventions can effectively address knowledge gaps among ID specialists regarding diagnosis and treatment of patients with NTM lung disease. Methods Two educational interventions, consisting of a text-based activity with interactive questions, and a video-based discussion between two experts, were developed and made available online. Educational impact of each intervention was assessed using a 3-question repeated pairs pre-/post-assessment study design. Data from a sampling of learners were collected from September 11, 2017 through January 17, 2018. Statistical analyses included a paired (within-physician) two-tailed t-test and McNemar’s χ2 statistic, with Cramer’s V to determine the overall effect of each intervention. Results Overall, a total of 1,273 ID specialist learners participated in the two activities from launch through April 30, 2018. Analysis demonstrated a significant improvement (P < 0.05) in overall knowledge with considerable educational impact (V = 0.195 and 0.259). Improvements in specific areas included (figure). Despite gains in knowledge, additional gaps were also identified: (1) Regarding treatment of M. abscessus lung disease, 18% were unable to discern between guideline recommended therapies for M. abscessus and MAC complex NTM, and an additional 14% would treat with a less aggressive, noncurative regimen (n = 211), and (2) regarding treatment of fibrocavitary MAC complex NTM; nearly one-third (31%) would treat a using a thrice-weekly regimen, despite an indication for a daily regimen (n = 114). Conclusion Participation in interactive text-based as well as video-based activities improved the ability of ID specialists to make evidence-based decisions in the care of NTM lung disease. The findings also uncovered educational needs that warrant further education in selecting appropriate therapeutic regimens particularly in cases where aggressive therapy is indicated. Disclosures E. Jackson, Medscape: Employee, Salary. P. Chatterjee, Medscape: Employee, Salary. S. Smith, BioFire Diagnostics: Independent Medical Education, Educational grant. K. Badal, Medscape: Employee, Salary. D. E. Griffith, Aradigm Corporation: Advisor/consultant and Speaker’s Bureau, Consulting fee and Speaker honorarium. Bayer Healthcare Pharmaceuticals: Advisor/consultant, Consulting fee. Grifols: Advisor/consultant and Speaker’s Bureau, Consulting fee and Speaker honorarium. Insmed Incorporated: Advisor/consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Grant recipient and Speaker honorarium.
24
Sharman, Jeff P., Versha Banerji, Laura Maria Fogliatto, Yair Herishanu, Talha Munir, Renata Walewska, George Follows, et al. "ELEVATE TN: Phase 3 Study of Acalabrutinib Combined with Obinutuzumab (O) or Alone Vs O Plus Chlorambucil (Clb) in Patients (Pts) with Treatment-Naive Chronic Lymphocytic Leukemia (CLL)." Blood 134, Supplement_1 (November 13, 2019): 31. http://dx.doi.org/10.1182/blood-2019-128404.
Full textAbstract:
Background: Acalabrutinib is a highly selective, covalent irreversible Bruton tyrosine kinase inhibitor with minimal activity against other kinases. Acalabrutinib has demonstrated durable responses as a single agent or combined with O in treatment-naïve (TN) CLL. Here, interim results are presented for the multicenter, open-label Phase 3 ELEVATE-TN study (NCT02475681), which evaluated the efficacy and safety of acalabrutinib + O vs acalabrutinib alone vs O + Clb in pts with TN CLL. Methods: Eligible pts had TN CLL requiring treatment per iwCLL criteria and were aged ≥65 y or <65 y with coexisting conditions (CIRS score >6, creatinine clearance <70 mL/min). Pts were randomized 1:1:1 to receive oral acalabrutinib (100 mg twice daily continuously) alone or combined with intravenous O (1000 mg on Days 1, 2 [split 100/900], 8, and 15 of Cycle 2, and Day 1 of subsequent 28-day cycles for a total of 6 cycles), or O plus oral Clb (0.5 mg/kg on Days 1 and 15 of each 28-day cycle for 6 cycles). Pts were stratified by del(17p) status, ECOG status (≤1 vs 2), and geographic region. The primary endpoint was independent review committee (IRC)-assessed progression-free survival (PFS) with acalabrutinib + O vs O + Clb. Key secondary endpoints included IRC-assessed PFS with acalabrutinib vs O + Clb, IRC-assessed overall response rate (ORR), overall survival (OS), and safety. Minimal residual disease (MRD) in peripheral blood or bone marrow was assessed in pts with investigator-assessed complete response (CR)/CR with incomplete marrow recovery (CRi). Crossover to acalabrutinib monotherapy was allowed for pts in the O + Clb arm with IRC-confirmed progression. Results: From 9/14/2015-2/8/2017, 535 pts were randomized to the acalabrutinib + O (n=179), acalabrutinib (n= 179), or O + Clb (n=177) arms. The median age was 70 y (range, 41-91); 69% had high- and 12% had very high-risk CLL IPI scores. At a median follow-up of 28 mo, acalabrutinib + O significantly prolonged PFS vs O + Clb (median not reached [NR] vs 22.6 mo; HR 0.10, 95% CI 0.06-0.18, P<0.0001), reducing the risk of progression or death by 90% (Figure). Acalabrutinib (median NR) also prolonged PFS vs O + Clb (HR 0.20, 95% CI 0.13-0.31, P<0.0001). Estimated 30-mo PFS rates with acalabrutinib + O, acalabrutinib, and O + Clb were 90%, 82%, and 34%, respectively. PFS improvement with acalabrutinib + O or acalabrutinib vs O + Clb was consistent across subgroups examined including del(17p) (HR [95% CI]; 0.13 [0.04-0.46]; 0.20 [0.06-0.64]). Median OS was not reached in any arm; (HR [95% CI]; acalabrutinib + O vs O + Clb, 0.47 [0.21-1.06], P=0.0577; acalabrutinib vs O + Clb, 0.60 [0.28-1.27], P=0.1556). In the acalabrutinib + O, acalabrutinib, and O + Clb arms, the estimated 30-mo OS rates were 95%, 94%, and 90%, respectively. Five pts (3%) in the acalabrutinib + O arm, 11 pts (6%) in the acalabrutinib arm, and 55 pts (31%) in the O + Clb arm had received a next therapy; 45 pts (25%) in the O + Clb arm crossed over to the acalabrutinib monotherapy arm. IRC-assessed ORR was higher with acalabrutinib + O (94%; 95% CI, 89.3%-96.5%) vs O + Clb (79%; 95% CI, 71.9%-83.9%; P<0.0001); the ORR with acalabrutinib monotherapy was 85%. CR rates were higher with acalabrutinib + O (13%) vs O + Clb (5%); there was 1 CR in the acalabrutinib monotherapy arm. MRD data will be presented. The median treatment duration was 27.7 mo for acalabrutinib + O (range, 2.3-40.3) and acalabrutinib (range, 0.3-40.2) and 5.6 mo (range, 0.9-7.4) for O + Clb. Common adverse events (AEs) are shown in the Table. AEs were similar between the acalabrutinib-containing arms. Infusion reactions were less frequent with acalabrutinib + O (13%) than with O + Clb (40%). AEs led to treatment discontinuation in 20 pts (11%) on acalabrutinib + O, 16 pts (9%) on acalabrutinib, and 25 pts (14%) on O + Clb. With >2 y of follow-up, 79.3% of pts in both the acalabrutinib-containing arms remain on single-agent acalabrutinib. AEs of interest (acalabrutinib + O or acalabrutinib vs O + Clb) were atrial fibrillation (any grade: 3% or 4% vs 1%), bleeding (any grade/Grade ≥3: 43%/2% or 39%/2% vs 12%/0%), and hypertension (Grade ≥3: 3% or 2% vs 3%). Conclusions: Acalabrutinib + O and acalabrutinib monotherapy significantly improved PFS vs O + Clb, with tolerable safety in pts with TN CLL. Despite cross over for disease progression in the O + Clb arm, a trend toward improved OS was observed in both acalabrutinib arms, though longer follow-up is needed. Disclosures Sharman: AbbVie: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; TG Therapeutics: Consultancy, Honoraria, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; Acerta: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Research Funding. Banerji:CIHR: Research Funding; LLSC: Research Funding; Research Manitoba: Research Funding; CCMF: Research Funding; CancerCare Manitoba/University of Manitoba: Employment; CAPhO: Honoraria; BIOGEN: Other: Licensing fee; Dana-Farber Cancer Institute: Other: Licencing fee; Gilead: Consultancy, Honoraria, Research Funding; Astra-Zeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Roche: Honoraria, Licensing fee, Research Funding; Abbvie: Consultancy, Honoraria. Herishanu:Janssen: Honoraria; AbbVie: Honoraria; Roche: Honoraria. Munir:Gilead: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Roche: Honoraria; Morphosys: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sunesis: Consultancy; Pharmacyclics: Other: TBC; Acerta: Membership on an entity's Board of Directors or advisory committees; Alexion: Honoraria; AbbVie: Honoraria. Walewska:Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Speakers Bureau; Takeda: Other: Travel grant; Novartis: Other: travel grant. Follows:Abbvie: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau. Karlsson:Skane University Hospital: Employment. Ghia:AbbVie: Consultancy, Honoraria, Research Funding; Acerta/AstraZeneca: Consultancy, Honoraria; Juno/Celgene: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria, Research Funding; Novartis: Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy; ArQule: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; Dynamo: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Corbett:Celgene: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Tauranga Hospital: Employment; Pathlab Waikato: Equity Ownership. Walker:Peninsula Health (public hospital): Employment; Alfred health (public hospital): Employment; Roche: Other: Travel grant. Jurczak:Incyte: Research Funding; Takeda: Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Research Funding; Roche: Research Funding; Gilead: Research Funding; Celgene: Research Funding; MorphoSys: Research Funding; Celtrion: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Servier: Research Funding. Salles:Epizyme: Consultancy, Honoraria; BMS: Honoraria; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis, Servier, AbbVie, Karyopharm, Kite, MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Other: Educational events. Janssens:Novartis: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Celgene: Speakers Bureau; abbvie: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; idem consultancy: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau. Cymbalista:AstraZeneca: Honoraria; Janssen: Honoraria; Sunesis: Research Funding; Roche: Research Funding; Gilead: Honoraria; Abbvie: Honoraria. Wierda:Juno Therapeutics: Research Funding; Janssen: Research Funding; Cyclcel: Research Funding; KITE pharma: Research Funding; Loxo Oncology Inc.: Research Funding; Genentech: Research Funding; Xencor: Research Funding; Acerta Pharma Inc: Research Funding; Pharmacyclics LLC: Research Funding; Sunesis: Research Funding; AbbVie: Research Funding; Miragen: Research Funding; Oncternal Therapeutics Inc.: Research Funding; Gilead Sciences: Research Funding; GSK/Novartis: Research Funding. Coutre:Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Astra Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Acerta: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Research Funding; BeiGene: Other: Travel, Accommodations, Expenses & Data Safety Monitoring Committee; Genentech: Consultancy. Pagel:AstraZeneca: Consultancy; Gilead Sciences: Consultancy; Pharmacyclics: Consultancy. Skarbnik:Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Verastem Oncology: Honoraria, Research Funding, Speakers Bureau; Kite Pharma: Honoraria, Speakers Bureau; Gilead Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Acerta: Research Funding; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Honoraria, Speakers Bureau; CLL Society: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Speakers Bureau; Novartis: Speakers Bureau. Kamdar:AstraZeneca: Consultancy; University of Colorado: Employment; Celgene: Consultancy; Seattle Genetics: Speakers Bureau; Pharmacyclics: Consultancy. Woyach:Janssen: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; AbbVie: Research Funding; Karyopharm: Research Funding; Loxo: Research Funding; Morphosys: Research Funding; Verastem: Research Funding. Izumi:AstraZeneca: Equity Ownership; Acerta Pharma: Employment, Equity Ownership, Patents & Royalties: Acalabrutinib patents. Munugalavadla:Acerta Pharma: Employment; Gilead Sciences: Equity Ownership; AstraZeneca: Equity Ownership. Patel:Acerta Pharma: Employment, Equity Ownership; AstraZeneca: Equity Ownership. Wang:Acerta Pharma: Employment; AstraZeneca: Equity Ownership. Wong:Acerta Pharma: Employment. Byrd:Genentech: Research Funding; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Novartis: Other: Travel Expenses, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Novartis: Other: Travel Expenses, Speakers Bureau; Novartis: Other: Travel Expenses, Speakers Bureau; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; Ohio State University: Patents & Royalties: OSU-2S; Ohio State University: Patents & Royalties: OSU-2S; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Genentech: Research Funding; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Genentech: Research Funding; Acerta: Research Funding; Acerta: Research Funding; Acerta: Research Funding; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Ohio State University: Patents & Royalties: OSU-2S; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; BeiGene: Research Funding; BeiGene: Research Funding; BeiGene: Research Funding; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau.
25
Pawlyn, Charlotte, Faith E. Davies, Walter M. Gregory, Alex J. Szubert, Sue E. Bell, Jacqueline Ouzman, Mark T. Drayson, et al. "Sequential Immunomodulatory Drug (IMiD) and Proteosome Inhibitor Therapy Improves Response Rates in Newly Diagnosed Multiple Myeloma: Preliminary Results From the Myeloma XI Trial." Blood 120, no. 21 (November 16, 2012): 335. http://dx.doi.org/10.1182/blood.v120.21.335.335.
Full textAbstract:
Abstract Abstract 335 Background Induction treatment for myeloma has focused on improving response rates and many centres have evaluated and used triplets of therapy based on either IMiD or proteosome inhibitor drugs. Other strategies rely on combining the two classes of novel agents and excellent response rates have been obtained. An alternative approach to this, which moves some way towards personalised therapy, is to use sequential combinations of the two classes of novel agents dependent on the response achieved. The aim of this approach is to maximise responses and, by so doing, improve survival. Methods In order to test this concept, we have carried out a trial, Myeloma XI, which compared responses to cyclophosphamide, thalidomide and dexamethasone (CTD) with cyclophosphamide, lenalidomide and dexamethasone (CRD). Following the randomised use of either of these triplets, given to maximum response, patients achieving no response (NC or PD) received further therapy with a triplet composed of cyclophosphamide, bortezomib and dexamethasone (CVD). In order to test if a bortezomib combination could improve the response of maximally treated patients, those with a suboptimal response (MR or PR) were randomised to either no further therapy or to CVD. For patients achieving ≥ VGPR no further induction was given. Younger fitter patients went on to receive HDM plus ASCT whereas older less fit patients did not. All patients were eligible for a maintenance randomisation to no maintenance, lenalidomide or lenalidomide/vorinostat maintenance. For patients receiving CVD, treatment was continued to a maximum of 8 cycles, with response being assessed using IMWG criteria after each cycle and therapy continued to maximum response or intolerance. Here we present the response rates for patients who have received CVD. Results At the time of this initial analysis 1424 patients have been randomised overall; 790 in the intensive pathway and 634 in the non-intensive pathway. Across both pathways, of the refractory patients with no response to induction treatment, an upgrade in response from NC or PD to ≥MR was seen after CVD treatment in 58% of patients, with 31% going on to achieve a VGPR or CR. In the other group of patients, those with a suboptimal response to induction treatment and randomised to receive CVD, 45% went on to achieve VGPR or CR. These patients reduced their paraprotein value by a mean of 74% from the start of CVD suggesting that the improvement in response is significant and not the result of patients marginally crossing the boundaries of response criteria. It seems that even in a group of maximally treated patients that response rates can be increased further by the use of a proteosome inhibitor drug. In the MRC Myeloma IX study the response rates at a similar time point for those treated with similar thalidomide based induction were PD/NC 7.1%, MR/PR 41.8%, VGPR/CR 37.5%. Assuming at least the same response rates in the current study then we calculate that it would be possible to get approximately 45% extra patients from MR/PR and 31% from PD/NC to ≥VGPR, equating to an approximate 21% increase in the ≥VGPR rate to 59% of the total patients. Conclusions We have demonstrated an improvement in response with the addition of a bortezomib based regimen in the group of patients who had a suboptimal response following induction chemotherapy with an IMiD based regimen. Particularly encouraging is the excellent rate of achievement of CR/VGPR in patients with no initial response to treatment. We anticipate that together this will significantly improve the percentage of patients achieving ≥VGPR, approximating 60% of all patients following induction, a response rate that should improve further following ASCT. Further follow up is required to know whether or not this will translate into an improvement in OS or PFS, however from previous studies we would expect this to be the case. Disclosures: Pawlyn: Celgene: Unrestricted educational grant Other. Off Label Use: Lenalidomide and vorinostat as maintenence therapy. Davies:Celgene: Honoraria, Speakers Bureau, Unrestricted educational grant, Unrestricted educational grant Other; Ortho Biotech: Honoraria, Speakers Bureau. Gregory:Celgene: Unrestricted educational grant Other. Szubert:Celgene: Unrestricted educational grant Other. Bell:Celgene: Unrestricted educational grant Other. Ouzman:Celgene: Unrestricted educational grant Other. Drayson:Celgene: Unrestricted educational grant Other. Owen:Celgene: Unrestricted educational grant Other. Jackson:Celgene: Honoraria, Unrestricted educational grant Other. Russell:Celgene: Unrestricted educational grant Other. Morgan:Ortho Biotech: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau, Unrestricted educational grant, Unrestricted educational grant Other.
26
Harrison, Claire, Joanna Baxter, Rebecca H. Boucher, Thomas McKerrell, Aimee Jackson, Rachel S. Fletcher, Adam J. Mead, et al. "Effects of Tamoxifen on the Mutant Allele Burden and Disease Course in Patients with Myeloproliferative Neoplasms - Results of the Tamarin Study." Blood 136, Supplement 1 (November 5, 2020): 33–35. http://dx.doi.org/10.1182/blood-2020-134764.
Full textAbstract:
Background Myeloproliferative neoplasms (MPN) commonly result from mutations in genes encoding the kinase JAK2 or the multi-functional protein CALR. In preclinical studies, estrogen receptor alpha (ERα) modulation restores normal apoptosis in JAK2V617F hematopoietic progenitors (HSPCs). Use of selective ER modulators (SERM) such as tamoxifen may permit the molecular reduction of MPNs. Methods TAMARIN is a Trials Acceleration Programme, Phase II, multicentre, single arm A'herns design clinical trial assessing tamoxifen's safety and activity in reducing molecular markers of disease burden in MPN male patients aged ≥60 years and post-menopausal female patients with stable blood counts, no history of thrombosis and ≥20% mutated JAK2V617F, CALR 5bp insertion or CALR 52bp deletion. Based on tamoxifen's safety profile in ER+ breast cancer, an oral dose of 20 mg once daily was initially given and progressively escalated to 40 mg, in addition to standard cytoreductive therapy (excluding treatments known to lower allele burden eg interferon). Mutant allele burden was measured after 12 and 24 weeks (w) of treatment. The A'herns success criteria required the primary outcome (>50% reduction in allele burden at 24w) be observed in ≥3 patients (Barosi Leuk. 2015). Patient blood (baseline, 12 and 24w) samples were collected and CD34+ HSPCs were isolated in a subset for RNA-Seq, which was also performed on HEL and UKE-1 JAK2V617F-mutated human cell lines treated with tamoxifen/vehicle. Apoptosis and oxidative phosphorylation (OXPHOS) were measured in SERM-treated cell lines for confirmation. Results and Discussion 38 patients (37% essential thrombocythaemia (ET), 29% polycythaemia vera (PV), 16% primary myelofibrosis (PMF), 13% post-PV MF and 5% post-ET MF) were recruited over 112w. 33 patients completed ≥24w of tamoxifen treatment, 1 was untreated, 1 discontinued following an unprovoked thrombotic event and 3 discontinued due to toxicity. 4 patients achieved the primary outcome and 6 additional patients met the secondary outcome (≥25% reduction)(A-B). Responders included 4 JAK2V617F PV males, a JAK2V617F PMF female and ET patients of both genders carrying JAK2V617F, CALRdel52 or CALRins5 mutations. 4 patients remain on trial treatment beyond 48w as they are considered to be deriving clinical benefit. Two grade 3 adverse events unrelated to tamoxifen, as well as 1 superficial thrombophlebitis and 1 deep vein thrombosis (grade 2) occurred on study. HSPC transcriptome seggregates responders and non-responders perfectly at baseline (C), suggesting a potential predictive signature of response. Pathway analysis of differentially-expressed genes shows enrichment of myeloid differentiation and hormone-dependent transcriptional complex assembly in responders at baseline. In contrast, chromosome segregation, DNA replication, and chromosome condensation pathways are enriched in non-responders. Gene-set enrichment analysis (GSEA) reveals increased apoptosis and oxidative phosphorylation (OXPHOS) signatures in responders at baseline (D). Upregulated genes in responders are associated with H3K4me1 modification whilst genes upregulated in non-responders are associated with H3K9me3, suggesting the possibility that chromatin modifications account for tamoxifen sensitivity. 24w after treatment, OXPHOS and ROS pathways are downregulated in responder HSPCs (E) but upregulated in non-responders (F), suggesting striking differences in the metabolism of HSPCs in both groups and/or the eradication of sensitive HSPCs in responders. Reduced OXPHOS pathways and deregulated expression of unfolded protein response (UPR) genes were confirmed in HEL and UKE-1 cells. In fact, tamoxifen induces dose-dependent apoptosis in HEL and UKE-1 cells, where serum deprivation or UPR inducers sensitize resistant cells to tamoxifen-induced apoptosis, which is associated with decreased OXPHOS and energy (ATP) production. Conclusions These results demonstrate the safety and activity of tamoxifen in reducing mutant allele burden in a subset of MPN patients who could be prospectively identified based on their transcriptomic signature at baseline. Tamoxifen can induce apoptosis of human JAK2V617F or CALR mutated HSPCs through metabolic and transcriptional effects. These results advocate for future studies to test the effects of SERMs in MPN with careful consideration of thrombotic risk. Disclosures Harrison: Roche: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Janssen: Speakers Bureau; AOP Orphan Pharmaceuticals: Honoraria; Promedior: Honoraria; Shire: Honoraria, Speakers Bureau; CTI Biopharma Corp: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; Sierra Oncology: Honoraria; Gilead Sciences: Honoraria, Speakers Bureau; Incyte Corporation: Speakers Bureau. Mead:CTI: Consultancy; Gilead: Consultancy; Celgene/BMS: Consultancy, Honoraria, Other: travel, accommodations, expenses, Research Funding; Novartis: Consultancy, Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau; Abbvie: Consultancy. Knapper:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ewing:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. McMullin:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy; Celgene: Consultancy; Abbvie: Membership on an entity's Board of Directors or advisory committees. Narayanan:Novartis: Other: Educational support to attend conferences; MSD: Speakers Bureau; Celgene: Other: Educational support to attend conferences; Alexion: Speakers Bureau; Takeda: Other: Educational support to attend conferences. Milojkovic:Incyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria. Drummond:Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Blueprint Medicine Corporation: Research Funding; Astellas: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. OffLabel Disclosure: Tamoxifen is a selective estrogen receptor modulator frequently used in estrogen receptor-positive breast cancer.
27
Boltivets, Serhii. "On the modeling of a national encyclopedic-and-educational service." Entsykpopedychnyi Visnyk Ukrainy [The Encyclopedia Herald of Ukraine] 11 (December 9, 2019): 31–39. http://dx.doi.org/10.37068/evu.11.3.
Full textAbstract:
The article defends the necessity to establish a national help service titled Navchannia Navprostets (Learn Direct). It would be a not-for-profit telephone line based on modern encyclopedias of Ukraine. The creation of such a service is justified by the Lifelong Learning as an international social movement, which in Ukraine is supervised by the Ukrainian Coordination Bureau of the International Public-State Program Adult Education in Ukraine. The concept of lifelong learning is upheld by the scientifically explained idea of a person’s ability to learn at any age. It has been identified by the Council of Europe as an important component of the social model of Europe. Accordingly, one of the tasks of the European states is to ensure the citizens’ aspirations for development and to receive lifelong education. The idea to start up a national help service in Ukraine is based on the experience of European countries, first of all, we mean a service in the UK (Learndirect).
28
Chiaretti, Sabina, Renato Bassan, Antonella Vitale, Loredana Elia, Alfonso Piciocchi, Cristina Puzzolo, Martina Canichella, et al. "Dasatinib-Blinatumomab Combination for the Front-Line Treatment of Adult Ph+ ALL Patients. Updated Results of the Gimema LAL2116 D-Alba Trial." Blood 134, Supplement_1 (November 13, 2019): 740. http://dx.doi.org/10.1182/blood-2019-128759.
Full textAbstract:
Background. The management of adult patients with Ph+ acute lymphoblastic leukemia (Ph+ ALL), including the elderly, has changed since the introduction of tyrosine kinase inhibitors (TKI). A significantly better survival is observed in patients who become minimal residual disease (MRD)-negative. Aims. To increase the rate of MRD-negative patients, we designed a front-line chemo-free induction-consolidation trial (D-ALBA, GIMEMA LAL2116) based on the combination of the second-generation TKI dasatinib with the bispecific monoclonal antibody blinatumomab. The primary endpoint of the study was the rate of patients who achieved a complete molecular remission (CMR) or a positive non-quantifiable (PNQ) disease after at least two cycles of blinatumomab. Secondary endpoints included disease-free survival (DFS), overall survival (OS), cumulative incidence of relapse (CIR) and safety. We also sought to evaluate the prognostic impact of additional genomic lesions - performed on diagnostic samples - and the potential changes in the immunologic compartment, in terms of T cells and T-regulatory cells (Tregs), evaluated by flow cytometry (CD3+/CD4+, CD3+/CD8+ and CD3+/CD4+/CD25+/FOXp3+, respectively). Methods. This multicenter phase II study enrolled Ph+ ALL patients aged 18 years or older, with no upper age limit. Prior to dasatinib, patients received a 7-day steroids pre-phase: steroids were continued for further 24 days and stopped at day 31. Dasatinib (140 mg/day) was administered as induction for 85 days. Thereafter, patients who obtained a complete hematologic response (CHR) received a post-induction consolidation treatment with blinatumomab at a flat dose of 28 μg/day. A minimum of 2 cycles was mandatory, while the administration of up to 3 additional cycles was allowed based on the response to blinatumomab and medical decision. Dasatinib was continued during treatment with blinatumomab. CNS prophylaxis was carried out during the whole treatment. Post-consolidation treatment was open. Results. Between May 2017 and January 2019, 63 patients have been enrolled. Median age was 54.5 years (range: 24.1-81.7), 54% were female, the median white blood cell count (WBC) was 42 x109/l (range: 0.63-63.5) and 65.1% carried the p190 fusion. Copy number aberration analysis showed that the most frequent lesion was, as expected, IKZF1 deletion (54%): 23.9% of patients were thus classified as IKZF1plus (i.e. IKZF1 and/or PAX5 and/or CDKN2A/B deletions). The median follow-up is 10 months (range: 0.9-21.5). So far, 61 patients have completed induction, 55 the 1st cycle of blinatumomab, 47 the 2nd cycle, 33 the 3rd, 26 the 4th and 17 the 5th. Two patients have gone off protocol for medical decision and toxicity, and 1 died during induction. At the end of the induction with dasatonib, 17/58 pts (29.3%) had a molecular response (6 CMR and 11 PNQ). At the primary endpoint (end of the 2nd cycle of blinatumomab), 27/47 (56.3%) had a molecular response (17 CMR and 10 PNQ). The rates of molecular responses further increased after subsequent cycles of blinatumomab: 65.7% after the 3rd cycle and 80% after the 4th cycle. ABL1 mutational analysis was carried out in 15 patients with evidence of a MRD increase: 8 cases were WT, while mutations were detected in 7 (6 T315I, and 1 E255K). All mutations but 1 occurred prior to the start of blinatumomab and all were "cleared" by blinatumomab. The analysis of the immunologic compartment carried out in 12 patients who completed all 5 cycles of blinatumomab showed a significant increase in the rate of CD8+ T cells (19.8% before the start of blinatumomab and 29% after the 5th cycle, p=0.04) and a significant reduction in the rate of Tregs (11% before blinatumomab and 3.7% after the 5th cycle, p=0.02). Overall, 5 relapses have been recorded (2 hematologic, 2 isolated CNS and 1 nodal). The 12-month OS and DFS are 94.2% and 87.8%. A significantly inferior DFS (61.4%, p=0.01) was observed in IKZF1plus cases: these patients were prone to develop deleterious mutations. So far, 12 patients have been allografted and no transplant-related mortality has been recorded. Conclusions. In the first chemo-free induction-consolidation protocol for adult Ph+ ALL patients of all ages based on a combination of a targeted and immunotherapeutic strategy, the rates of molecular responses and survival are highly promising; patients harboring IKZF1 plus represent, also in this setting, a clinical challenge. Disclosures Chiaretti: Pfizer: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees. Bassan:Amgen Inc.: Honoraria; Incyte: Honoraria; Pfizer: Honoraria; Shire: Honoraria. Bonifacio:BMS: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Incyte: Honoraria. Vignetti:Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Educational Training; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Educational Training. Rambaldi:Omeros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Italfarmaco: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, travel support. Foà:Celltrion: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau.
29
Caglayan, Caglar, Jesse Dixon, Anna Wall, Gilles A. Salles, Eva Hoster, Wolfgang Hiddemann, Michael Herold, et al. "A Multistate Survival Analysis for Patients with Follicular Lymphoma (FL) Using 13 First-Line Randomized Trials from FL Analysis of Surrogate Hypothesis (FLASH) Group." Blood 134, Supplement_1 (November 13, 2019): 2812. http://dx.doi.org/10.1182/blood-2019-122328.
Full textAbstract:
Introduction: Most patients with newly diagnosed FL treated with rituximab (R) alone or R + chemotherapy will experience prolonged progression-free survival and overall survival (OS), but it remains unclear what factors have the greatest influence on FL-associated and other causes of death in this patient population. We utilized individual patient data from 13 first-line randomized clinical trials from the FLASH database to perform a comprehensive multistate survival analysis to examine and quantify the relationships between clinical characteristics, treatment response, and early, intermediate, and late FL outcomes. Methods: The multistate survival analysis model defined states for "Alive after beginning Induction Treatment (TX)", "Alive after beginning Maintenance TX", "Death due to FL", and "Death from Other Causes" (Figure 1). We used the Aalen-Johansen estimator, a generalization of the Kaplan-Meier estimator, to calculate the likelihood of being in each model state and estimate the course of FL over time. Making no assumptions on the probability distributions and capable of coping with censored observations, the Aalen-Johansen estimator is a convenient and reliable nonparametric estimator for clinical data. Results: Among 7,465 FL patients with median age 56 (range 18-90) years, 49.2% were female; 28.7% Stage I-III, 71.3% Stage IV, and FLIPI was 0-1 (20.0%), 2 (36.8%), ≥ 3 (43.2%). Following initiation of induction treatment, 2-, 5- and 10-year death rates were 1.7%, 3.8%, and 5.8% due to FL, and 0.7%, 2.1%, and 4.8% from other causes (Figure 2). Death rates at 2, 5, and 10 years due to FL and other causes for subgroups based on clinical characteristics and treatment response are shown in Table 1. Notably, patients > 70 years and patients with FLIPI ≥ 3 had worse outcomes and patients achieving CR at 18, 24, and 30 months experienced improved outcomes. Conclusion: This is the largest study using data from randomized trials to quantify the impact of clinical factors on early, intermediate and late mortality by cause of death. We demonstrated that age > 70 years and FLIPI ≥ 3 were linked to increased FL-associated death and response to TX distinguished patients with favorable and poor outcomes. Future analyses should quantify the impact of predictors on the rate/time of FL outcomes in multivariable models. Disclosures Salles: Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Amgen: Honoraria, Other: Educational events; BMS: Honoraria; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis, Servier, AbbVie, Karyopharm, Kite, MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Epizyme: Consultancy, Honoraria; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events. Hoster:Janssen: Research Funding; Roche Pharma AG: Other: Travel Support. Hiddemann:Bayer: Research Funding; Gilead: Consultancy, Honoraria; Vector Therapeutics: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria. Herold:Roche: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Gilead: Honoraria; Celgene: Honoraria. Morschhauser:Servier: Consultancy; Gilead: Consultancy; Janssen: Honoraria; Roche/Genentech: Consultancy; BMS: Honoraria; Celgene: Honoraria. Rummel:Roche Pharma AG: Honoraria, Research Funding; Celgene: Honoraria; Janssen: Honoraria; Sandoz: Honoraria. Kimby:AbbVie,: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Jansen: Membership on an entity's Board of Directors or advisory committees; Gilead: Other: educational lectures. Vitolo:Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Gyan:Pfizer: Honoraria. Ladetto:Celgene: Honoraria; Roche: Honoraria; Janssen: Honoraria; Abbvie: Honoraria; Acerta: Honoraria; Sandoz: Honoraria. Nielsen:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Flowers:AstraZeneca: Consultancy; BeiGene: Consultancy, Research Funding; Eastern Cooperative Oncology Group: Research Funding; Burroughs Wellcome Fund: Research Funding; AbbVie: Consultancy, Research Funding; Optimum Rx: Consultancy; V Foundation: Research Funding; Pharmacyclics/Janssen: Consultancy, Research Funding; Bayer: Consultancy; Gilead: Consultancy, Research Funding; TG Therapeutics: Research Funding; Denovo Biopharma: Consultancy; Acerta: Research Funding; National Cancer Institute: Research Funding; Millenium/Takeda: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Spectrum: Consultancy;
30
Adams, David W. "A Year of Crisis: Memory and Meaning in a Navajo Community's Struggle for Self-Determination." American Indian Culture and Research Journal 42, no. 4 (October 1, 2018): 113–30. http://dx.doi.org/10.17953/aicrj.42.4.adams.
Full textAbstract:
In 1979, when a remote Diné (Navajo) community in New Mexico learned that under new federal self-determination guidelines it could establish its own school, it jumped at the opportunity. But just two years after the school's founding, conditions were so bad that teachers and community, in fear of a Bureau of Indian Affairs (BIA) takeover, mounted a full-scale rebellion against the school's leadership. Now, some thirty-five years later, the author, who witnessed the events described, recalls in intimate and painful detail this story—a moment in Native American educational history, he suggests, not without meaning for other Indigenous communities' ongoing quest for greater educational sovereignty.
31
Dempsey, Ian, and Phil Foreman. "Trends and Influences in the Integration of Students with Disabilities in Australia." Australasian Journal of Special Education 19, no. 2 (January 1995): 47–53. http://dx.doi.org/10.1017/s1030011200023459.
Full textAbstract:
Although support for the integration of students with disabilities has increased in the past 20 years in Australia, it has not been clear to what extent this support has resulted in less restrictive educational placements for these students. This paper reports the results of an analysis of trends in the placement of students with disabilities in Australian schools. The paper also discusses the influence on this educational placement by sex, age and number of disabilities of school students, and their State of residence. This discussion follows the analysis of portions of a national data set compiled by the Australian Bureau of Statistics that related to people with disabilities.
32
Erdes, S., E. Agafonova, D. Rumiantceva, S. Davidian, E. Zemerova, A. Kulikov, O. Markova, E. Lukyanova, and V. Achikyan. "POS0903 CLINICAL AND RADIOLOGICAL MANIFESTATIONS OF COXITIS IN PATIENTS WITH ANKYLOSING SPONDYLITIS (AS) TREATED WITH TNF-ALPHA INHIBITOR GOLIMUMAB: RESULTS OF A 24-MONTHS OBSERVATION (GO-COX STUDY)." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 709–10. http://dx.doi.org/10.1136/annrheumdis-2021-eular.299.
Full textAbstract:
Background:Coxitis (hip joint inflammation) in AS is associated with worse BASFI scores due to hip joint involvement and more severe axial disease [1]. Radiological index of BASRI-hip, US and MRI findings may be used for evaluation of hip joint impairment [2, 3, 4]. Number of studies on coxitis in AS patients treated with biologics was limited at time of this study initiation.Objectives:To evaluate clinical changes measured by BASFI, BASMI, BASDAI, ASDAS-CRP and radiological changes in AS patients with coxitis (BASRI-hip, hip MRI [STIR- and T1-weighted sequences], hip US) after 12 and 24 months of treatment with TNF alpha inhibitor golimumab from baseline.Methods:A non-interventional prospective cohort study. Bio-naïve patients with AS and coxitis were treated with golimumab according to daily clinical practice in 5 clinics across Russia and followed up for 24 months. 39 patients participated. This analysis includes data from 30 patients who completed the follow up. The whole cohort’s data to be presented after consolidation of safety data. MRI and US data were collected for 12 months in up to 28 of 30 patients. The primary endpoint was mean change of BASFI which was expected to be -2.5 (± 2.12) from baseline at week 52 weeks (12 months) of therapy [5]. The power of the study was 90% with minimum sample size of 18 patients. Student’s paired t-criteria, Wilcoxon signed rank test were used to compare quantitave and Chi-square test for qualitative variables.Results:Majority of participants (66,7%; 20 out of 30) were male, with mean (SD) age of 33.2 (9.4) years, mean (SD) duration of AS was 36.2 (42.1) months, mean (SD) duration of coxitis was 36.9 (44.1) months. Baseline mean (SD) scores were: BASFI 3.9 (2.5), BASMI 3.1 (2.5), BASDAI 4.9 (2.0), ASDAS-CRP 3.5 (1.2). Changes of mean clinical scores from baseline after 12 and 24 months of treatment with golimumab were: ΔBASFI= -2.2 (p=0.0001), -2.1 (p=0.0000); ΔBASMI= -1.5 (p=0.0000), -1,8 (p=0.0000); ΔBASDAI= -3.0 (p=0.0000), -3.1 (p=0.0000); ΔASDAS-CRP= -2.0 (p=0.0000), -2.1 (p=0.0000), correspondingly (n=30). The clinical results (medians, interquartile ranges, min and max) are presented below.Baseline mean (SD)/median BASRI-hip was 1.1 (0.8)/1.0 on the right and on the left. Changes of mean/median BASRI-hip score at 12 and 24 months compared to baseline were: 0.3/0.0 (n=25; p=0.2344) and 0.3/0.0 (n=25; p=0.1368) on the right; 0.4/0.0 (n=25; p=0.0352) and 0.4/1.0 (n=25; p=0.0735) on the left. Rates of patients with MRI and US findings are presented below.HipMRI, paired analysisPatients (%), n=27Patients (%), n=23BaselineAt 6 monthsBaselineAt 12 monthsRightNo findings33.348.139.156.5Subchondral bone marrow edema (SBME)37.011.134.88.7Joint effusion74.125.9*73.917.4*Enthesitis33.311.134.821.7Fatty degeneration37.055.634.852.2LeftNo findings29.651.930.452.2SBME18.53.78.74.3Joint effusion63.022.2*60.921.7Enthesitis22.218.517.421.7Fatty degeneration33.355.630.452.2HipUS, paired analysisPatients (%), n=28Patients (%), n=27BaselineAt 6 monthsBaselineAt 12 monthsRightNo findings14.350.0*18.551.9*Joint effusion46.425.051.911.1*Enthesitis25.014.318.514.8LeftNo findings14.350.0*18.555.6*Joint effusion42.928.648.125.9Enthesitis17.917.911.118.5*p<0.05Conclusion:Therapy with TNF alpha inhibitor golimumab for 24 months in AS patients with coxitis was accompanied with statistically significant improvement of clinical scores with primary endpoint achieved (mean BASFI change -2.5 at 12 months), improvement of MRI and US findings without obvious structural progression measured with BASRI-hip score compared to baseline.References:[1]Cruyssen B.V. et al. Rheumatology 2010; 49: 73-81.[2]Boonen A. et al. J Rheumatol 2009; 36; 1249-1255.[3]Cruyssen B.V. et al. Curr Opin Rheumatol 2013, 25: 448-454.[4]Zhen-Guo H. et al. European Journal of Radiology 82 (2013) 1487-1493.[5]Konsta et al. Clin Rheumatol (2013) 32:1229-1232.Braun J. et al. Ann Rheum Dis 2012; 71: 661–667.Disclosure of Interests:Shandor Erdes Speakers bureau: Paid as a speaker during educational activities supported by pharmaceutical companies (MSD, Pfizer, AbbVie, BIOCAD), Ekaterina Agafonova Speakers bureau: Paid as a speaker during educational activities supported by pharmaceutical companies (MSD)., Daria Rumiantceva Speakers bureau: Paid as a speaker during educational activities supported by pharmaceutical companies (Novartis), Satenik Davidian: None declared, Elena Zemerova Speakers bureau: Paid as a speaker during educational activities supported by pharmaceutical companies (MSD, Pfizer), Aleksey Kulikov Speakers bureau: Paid as a speaker during educational activities supported by pharmaceutical companies (MSD, AbbVie, UCB, BIOCAD, Novartis, Sanofi), Olga Markova Speakers bureau: Paid as a speaker during educational activities supported by pharmaceutical companies (MSD, Novartis, Medac, GSK), Ekaterina Lukyanova Employee of: MSD Pharmaceutical LLC (Russia), Director of Medical Affairs., Vladimir Achikyan Employee of: MSD Pharmaceutical LLC (Russia), Therapeutic Area Lead
33
Thapa, Surya Bahadur. "The Educational Kuznets Curve: A Case of Nepal." Tribhuvan University Journal 27, no. 1-2 (December 30, 2010): 159–66. http://dx.doi.org/10.3126/tuj.v27i1-2.26399.
Full textAbstract:
Education is among the basic human needs and one of the components of well being in the modern world. Equal distribution of education is of great interest in public policy analysis. Spending in education represents substantial share of government revenue. The inequality in educational distribution represents large welfare loss. The purposes of this article are three folds. First, it calculates average years of schooling. Second, it estimates educational inequality in terms of standard deviation of schooling. Third, it examines the Educational Kuznets Curve in case of Nepal and answers the question: does it fit? This is quantitative study based on the secondary data collected and published by Central Bureau of Statistics. The study finds that the average years of schooling are increasing over the census years. It stood at 0.125 years in 1952 for all population and 0.245 and 0.019 respectively for males and females. The same data for all population, males and females for the year 2001are 4.385, 5.119, and3.083 years respectively. The data on standard deviation of schooling show that they are all in increasing trend from the census year 1952 to Census Year 2001.With the help of econometric test of both linear and nonlinear quadratic equations, this study concludes that the Educational Kuznets Curves does not exist in Nepal due to very low average years of schooling.
34
McGowan, Brenda. "“A Right to Childhood” the U.S. Children's Bureau And Child Welfare, 1912–1946." Children and Youth Services Review 21, no. 3 (March 1999): 262–63. http://dx.doi.org/10.1016/s0190-7409(99)90083-x.
Full text
35
Pasquini, Marcelo C., Frederick L. Locke, Alex F. Herrera, Tanya Siddiqi, Armin Ghobadi, Krishna V. Komanduri, Zhen-Huan Hu, et al. "Post-Marketing Use Outcomes of an Anti-CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy, Axicabtagene Ciloleucel (Axi-Cel), for the Treatment of Large B Cell Lymphoma (LBCL) in the United States (US)." Blood 134, Supplement_1 (November 13, 2019): 764. http://dx.doi.org/10.1182/blood-2019-124750.
Full textAbstract:
Introduction Axi-cel is approved in the US for the treatment of adult patients with relapsed or refractory large B cell lymphoma after 2 or more lines of systemic therapy. A post-marketing study is ongoing in the US utilizing the infrastructure created by the Center for International Blood and Marrow Transplant (CIBMTR) for post-approval safety and efficacy assessment and to follow these patients for 15 years through the established cellular therapy registry. This is the first year analysis of this study. Methods From October 18, 2017 to May 1, 2019, 453 axi-cel recipients were voluntarily reported to the CIBMTR. Of these, 295 patients from 43 US centers that have at least the first follow-up assessment submitted at 3 months were included in this analysis. Median follow-up was 6 months (range, 1-14 months). Results The median age overall was 61 years, 101 (34%) patients were ≥ 65 years, and 197 (67%) patients were male (Table 1). Baseline clinical characteristics included Eastern Cooperative Oncology Group (ECOG) performance score 0-1 (77%), transformed lymphoma (27%), double-hit lymphoma (36%), prior autologous transplant (34%), and chemotherapy-resistant disease (66%) prior to axi-cel. The median time from diagnosis to axi-cel infusion was 18 months (range 2-274 months). Overall response rate (ORR) was 70% (complete response [CR] 52% and partial response [PR] 18%). Patients ≥ 65 years were generally comparable vs younger patients with a slightly better CR rate (62% vs 46%, p=0.03) but similar overall response rate (CR+PR, 75% vs 67%, p=0.26). Cytokine release syndrome (CRS) of any grade was reported in 83% of patients. Incidence of Grades ≥ 3 CRS according to Lee et al 2014 was 11%, and was 14% according to American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading (Table 2). Two patients died due to CRS. Median time to any grade CRS was 3 days (range, 1-17 days), and 94% of CRS cases resolved with a median duration of 7 days (range, 1-121 days). Among patients with CRS, tocilizumab, corticosteroids and siltuximab were used in 70%, 26% and 1% of cases, respectively. Neurologic adverse events (AEs) of any grade occurring after axi-cel infusion were reported in 181 (61%) patients. One patient was reported to die from cerebral edema. Additional information on neurologic AE severity will be presented. The median time to onset of any grade neurologic AEs was 6 days (range, 1-82 days), and 88% resolved by time of data submission with a median duration of 8 days (range, 1 to 105 days). Corticosteroids were used in 56% of patients for treatment. Patients ≥ 65 years had comparable CRS (85% vs 82%, p=0.62), grades ≥ 3 CRS (13% vs 9%, p=0.62), and neurologic AEs (68% vs 58%, p=0.13) vs patients < 65 years of age. Prolonged cytopenias (thrombocytopenia and neutropenia), as defined by an inability to recover within 30 days after the administration of axi-cel, occurred in 7% of patients. Preliminary data reveals 6 patients (2%) reported subsequent neoplasms: myelodysplasia (n=3), lung cancer (n=1), neuroendocrine tumor (n=1), and cutaneous squamous cell carcinoma (n=1); additional details, including pre-existing risk factors, will be addressed when the updated analysis is presented. Conclusion Post-approval axi-cel use reported in this registry study in the US, when compared to the registrational ZUMA-1 trial, includes a larger proportion of older patients, patients with transformed or double-hit lymphoma, and patients with a worse performance status. Despite these differences, best responses and toxicities are comparable to those reported for the ZUMA-1 trial. CRS severity assessment varied based on the grading method utilized, with a slightly higher rate of grade 3 CRS based on ASTCT Consensus Grading compared with Lee et al 2014. The safety and efficacy outcomes of patients ≥ 65 years at this early stage are comparable to those of younger patients, although further analysis with more follow-up is warranted. Disclosures Pasquini: Novartis: Research Funding; Kit Pharma: Research Funding; BMS: Research Funding; Pfizer: Other: Advisory Board; Amgen: Consultancy; Medigene: Consultancy. Locke:Cellular BioMedicine Group Inc.: Consultancy; Kite: Other: Scientific Advisor; Novartis: Other: Scientific Advisor. Herrera:Pharmacyclics: Research Funding; Kite Pharma: Consultancy, Research Funding; Immune Design: Research Funding; Merck: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; AstraZeneca: Research Funding; Adaptive Biotechnologies: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding. Siddiqi:Seattle Genetics: Speakers Bureau; BeiGene: Research Funding; Celgene: Research Funding; TG Therapeutics: Research Funding; Kite: Research Funding; Astra Zeneca: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie company: Consultancy, Research Funding, Speakers Bureau; Juno: Consultancy, Research Funding; Janssen: Speakers Bureau. Ghobadi:Celgene: Consultancy; Wugen: Consultancy; Kite Pharma a Gilead Company: Consultancy, Research Funding, Speakers Bureau; EUSA: Consultancy. Dong:Gilead Inc: Other: Own Stock; Kite Pharma: Employment. Nikiforow:Kite/Gilead: Honoraria; Novartis: Honoraria; NKarta: Honoraria. Purdum:Kite Pharma: Employment. Horowitz:Sanofi: Other: Unrestricted educational and research grant, Research Funding; Chimerix: Other: Unrestricted educational and research grant; CSL Behring: Other: Unrestricted educational and research grant, Research Funding; Regeneron: Other: Unrestricted educational and research grant; Kite Pharma/Gilead: Other: Unrestricted educational and research grant, Research Funding; Daiichi Sankyo: Other: Unrestricted educational and research grant; GlaxoSmithKline: Other: Unrestricted educational and research grant; Janssen: Other: Unrestricted educational and research grant, Research Funding; Gamida Cell: Other: Unrestricted educational and research grant, Research Funding; Actinium: Other: Unrestricted educational and research grant; Amgen: Other: Unrestricted educational and research grant; Bristol-Myers Squibb: Other: Unrestricted educational and research grant, Research Funding; Magenta: Consultancy, Other: Unrestricted educational and research grant; Mesoblast: Other: Unrestricted educational and research grant, Research Funding; Miltenyi Biotech: Other: Unrestricted educational and research grant, Research Funding; Oncoimmune: Other: Unrestricted educational and research grant; Pharmacyclics: Other: Unrestricted educational and research grant; Seattle Genetics: Other: Unrestricted educational and research grant; Shire: Other: Unrestricted educational and research grant. Hooper:Kite Pharma Inc: Employment, Other: Owner Stock. Kawashima:Kite: Employment. Jacobson:Bayer: Consultancy, Other: Travel Expenses; Novartis: Consultancy, Honoraria, Other: Travel Expenses; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel Expenses, Research Funding; Precision Biosciences: Consultancy, Other: Travel Expenses; Pfizer: Consultancy, Research Funding; Humanigen: Consultancy, Other: Travel Expenses; Celgene: Consultancy, Other: Travel Expenses.
36
Schuster, Michael W., Miguel A. Canales, Jason Westin, Josée M. Zijlstra, George A. Follows, Reem Karmali, Nagesh Kalakonda, et al. "Selinexor Efficacy and Safety Are Independent of Renal Function in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL): A Post-Hoc Analysis from the Pivotal Phase 2b Sadal Study." Blood 136, Supplement 1 (November 5, 2020): 34–35. http://dx.doi.org/10.1182/blood-2020-137025.
Full textAbstract:
Introduction: Selinexor is a first-in-class Selective Inhibitor of Nuclear Export (SINE) that blocks XPO1, forcing the nuclear retention and re-activation of tumor suppressor proteins including p53, p73, FOXO, IkB and Rb. The phase 2b SADAL study included 134 patients with relapsed or refractory DLBCL with single agent oral selinexor twice weekly. The overall response rate (ORR) was 29.1%, median duration of response (DOR) was 9.3 months and the median overall survival (OS) was 9 months. Based on these data, selinexor was recently approved by the US FDA for the treatment of relapsed or refractory DLBCL, de novo or transformed from follicular lymphoma. Patients with DLBCL tend to have a number of comorbidities, including poor renal function, which can require a reduction in the dose of intensive chemotherapy as well as lenalidomide, leading to inferior outcomes. Selinexor is not metabolized nor cleared by the kidneys and has been demonstrated to be safe and active in patients with myeloma and renal dysfunction. We performed post-hoc analyses of the SADAL study to determine the efficacy and safety among patients stratified by renal function at baseline. Methods: The SADAL study is multi-center, open-label Phase 2b study that enrolled patients with DLBCL previously treated with 2-5 lines of therapy. Patients may have progressed post-stem cell therapy (SCT) or were not candidates for SCT. In this study, 60 mg of selinexor was administered twice weekly until disease progression. The primary endpoint was ORR, and other endpoints included DOR, OS, and safety assessments. For the current analysis, outcomes were assessed according to baseline renal function as estimated by the Cockroft-Gault formula for creatinine clearance (CrCl). Groups included those with reduced (CrCl ≤60 mL/min) and normal (CrCl >60 mL/min) renal function. Results: Of 134 patients, 37 (28%) had a reduced baseline CrCl (≤60 mL/min) while 97 (72%) had CrCl >60 mL/min. The median age of patients with reduced CrCl was 74 years with 70% ≥70 years, while the median for those with normal CrCl was 65 years, with 35% ≥70 years. De novo and transformed DLBCL showed similar renal function levels: 78% and 22% with reduced CrCl and 76% and 24% with normal CrCl. Of patients with reduced CrCl, the DLBCL subtype was 41% GCB and 57% non-GCB compared to 50% and 46% in patients with normal CrCl. The group of patients with reduced CrCl had baseline ECOG performance status of 2 in 16% vs 11% in those with normal CrCl. Treatment with selinexor demonstrated a similar ORR in patients with a baseline reduced CrCl (29.7%) versus normal CrCl (28.9%). A complete response (CR) was observed in 8 (21.6%) patients with reduced and 10 (10.3%) patients with normal CrCl. The median duration of response (DOR) in patients who had reduced CrCl was 23.0 months compared to 9.2 months in patients with normal CrCl. The median progression-free survival (PFS) was 3.5 months (95% CI 1.7, 24.8) and 2.3 months (95% CI 1.9, 3.7) and overall survival was 7.8 months and 9.1 months in patients with reduced CrCl and those with normal CrCl. The most common grade ≥3 treatment-related AEs for patients with reduced versus normal CrCl were thrombocytopenia (45.9% vs. 38.1%), nausea (5.4% vs. 6.2%), and fatigue (8.1% vs. 11.3%). There was no clinically significant increase in treatment-related serious adverse events (21.6% vs. 20.6%) and adverse events leading to discontinuation (10.8% vs. 7.2%) in patients with reduced or normal CrCl, respectively. Conclusions: Selinexor showed similar anti-DLBCL activity and tolerability in patients with relapsed/refractory DLBCL with a reduced renal function (CrCl <60 mL/min) compared to those with normal (CrCl ≥60 mL/min) renal function. No dose adjustments are required in patients with renal dysfunction and DLBCL who are treated with selinexor. Disclosures Schuster: Amgen, Abbvie, Gilead, Takeda, Celgene, Pharmacyclics, Astellas, Verastem, Merck, Novartis, Takeda, Genentech,, Seattle Genetics: Other: Personal Fees; Karyopharm: Membership on an entity's Board of Directors or advisory committees. Canales:Novartis: Honoraria; Janssen: Honoraria; Novartis: Honoraria; iQone: Honoraria; Sandoz: Speakers Bureau; Karyopharm: Honoraria; Janssen: Speakers Bureau; Janssen: Honoraria; Roche: Speakers Bureau; Takeda: Speakers Bureau; Janssen: Speakers Bureau; Roche: Speakers Bureau; Sandoz: Speakers Bureau; Takeda: Speakers Bureau; Celgene: Honoraria; Roche: Honoraria; Sandoz: Honoraria; Sandoz: Honoraria; Gilead: Honoraria; Roche: Honoraria; Karyopharm: Honoraria. Westin:Novartis: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Curis: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Astra Zeneca: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Morphosys: Consultancy, Research Funding; Amgen: Consultancy; 47: Research Funding. Zijlstra:Roche: Research Funding. Follows:Karyopharm, Roche, Abbvie, Astrazeneca, Janssen, BMS: Membership on an entity's Board of Directors or advisory committees. Karmali:Takeda: Research Funding; AstraZeneca: Speakers Bureau; Karyopharm: Honoraria; BeiGene: Speakers Bureau; BMS/Celgene/Juno: Honoraria, Other, Research Funding, Speakers Bureau; Gilead/Kite: Honoraria, Other, Research Funding, Speakers Bureau. Kalakonda:Gilead, Janssen, Karyopharm: Honoraria; Verastem, Gilead, Celgene, Roche: Research Funding. Goy:AbbVie: Research Funding; Celgene: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: leadership role, Research Funding; Acerta: Consultancy, Honoraria, Other: leadership role, Research Funding; MD Anderson: Research Funding; Xcenda: Consultancy; Kite, a Gilead Company: Consultancy, Current equity holder in publicly-traded company, Honoraria, Other: leadership role, Research Funding; Regional Cancer Care Associates/OMI: Current Employment; Bayer: Research Funding; PracticeUpdate Oncology: Consultancy; RCCA/OMI: Current Employment; Morphosys: Research Funding; Karyopharm: Research Funding; Genentech/Roche: Research Funding; Constellation: Research Funding; CALBG: Research Funding; Infinity Verastem: Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: leadership role, Research Funding; COTA: Consultancy, Current equity holder in publicly-traded company, Other: leadership role; Hackensack UMC and University of Nebraska: Research Funding; Infinity: Research Funding. Casasnovas:Takeda: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Gilead: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Roche: Consultancy, Honoraria, Other: travel, accomodations, expenses, Research Funding; Abbvie: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Thieblemont:Cellectis: Speakers Bureau; Roche, Amgen, Kyte Gilead, Celgene, Abbvie, Novartis, Cellectis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Roche, Hospita: Research Funding. Cavallo:Takeda, Janssen: Membership on an entity's Board of Directors or advisory committees; Gilead: Other: Speaker Fee. Hill:Celgene: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; AstraZenica: Consultancy, Honoraria, Research Funding; Beigene: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Takeda: Research Funding. Tilly:BMS: Honoraria. Jaeger:Novartis: Consultancy, Honoraria, Research Funding; Gilead: Honoraria, Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding; Karyopharm: Honoraria; AbbVie: Honoraria; F. Hoffmann-La Roche: Honoraria, Research Funding; Miltenyi: Consultancy, Honoraria; CDR Life AG: Consultancy, Research Funding. Gurion:JC Health CARE: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Takeda Pharmaceuticals: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria; Medison: Consultancy, Honoraria. Caimi:Celgene Corp: Other: Incyte Corporation - Ownership - Pharmacyclics, Inc. - Ownership - Celgene Corp. - Other, Speakers Bureau; ADC Therapeutics: Research Funding; Genentech: Research Funding. Martin:Kite: Consultancy; Morphosys: Consultancy; I-MAB: Consultancy; Janssen: Consultancy; Sandoz: Consultancy; Regeneron: Consultancy; Incyte: Consultancy; Karyopharm: Consultancy, Research Funding; Teneobio: Consultancy; Celgene: Consultancy; Bayer: Consultancy; Cellectar: Consultancy; Beigene: Consultancy. Davies:Roche, Acerta Pharma, AstraZeneca, Celgene, Gilead, ADC Therapeutics, Gilead: Research Funding; Roche, Celgene, Kite Pharma, Acerta, Karyopharma, Regeneron, Incyte: Consultancy; Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Celegene, Roche, Kite Pharma, Celegene: Honoraria. Smith:TG Therapeutics: Consultancy, Research Funding; Janssen: Consultancy; Celgene: Consultancy, Research Funding; BMS: Consultancy; Karyopharm: Consultancy, Research Funding; FortySeven: Research Funding; Pharmacyclics: Research Funding; Acerta: Research Funding; Genentech/Roche: Consultancy, Other: Support of parent study and funding of editorial support, Research Funding. Collins:BeiGene: Consultancy; MSD: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Speakers Bureau; Taekda: Consultancy, Honoraria, Other: travel, accommodations, expenses, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria; ADC Therapeutics: Consultancy, Honoraria; Celleron: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Speakers Bureau; Celgene: Research Funding; Roche: Consultancy, Honoraria, Other: travel, accommodations, expenses , Speakers Bureau; Amgen: Research Funding. Salles:Epizyme: Consultancy; Gilead: Consultancy, Honoraria, Other: Participation in educational events; Abbvie: Consultancy, Honoraria, Other: Participation in educational events; Janssen: Consultancy, Honoraria, Other: Participation in educational events; Kite: Consultancy, Honoraria, Other; Debiopharm: Consultancy; Celgene: Consultancy, Honoraria, Other: Participation in educational events; Karyopharm: Consultancy; Genmab: Consultancy; Amgen: Honoraria, Other: Participation in educational events; Autolus: Consultancy; MorphoSys: Consultancy, Honoraria, Other; Novartis: Consultancy, Honoraria, Other; F. Hoffman-La Roche Ltd: Consultancy, Honoraria, Other; Bristol Myers Squibb: Consultancy, Other; Takeda: Consultancy, Honoraria, Other. Ma:Karyopharm: Current Employment, Current equity holder in private company. Corona:Karyopharm: Current Employment. Saint-Martin:Karyopharm: Current Employment. Joshi:Karyopharm Therapeutics Inc: Consultancy. Chamoun:Karyopharm: Current Employment. Wang:Curis: Ended employment in the past 24 months; Karyopharm: Current Employment. Shah:Karyopharm: Current Employment, Current equity holder in publicly-traded company. Shacham:Karyopharm: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide containing nuclear transport modulators and uses, and pending patents PCT/US12/048319, 499/2012, PI20102724, and 2012000928) . Kauffman:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees.
37
Cappellini, Maria Domenica, Photis Beris, Pierre Brissot, John B. Porter, Ali Taher, Patty Peterson, and Elaine Rudell. "Iron Overload Diagnosis and Management Among Clinicians: International Survey Showing Gaps In Knowledge and Need for Continuing Educational Programs." Blood 116, no. 21 (November 19, 2010): 2562. http://dx.doi.org/10.1182/blood.v116.21.2562.2562.
Full textAbstract:
Abstract Abstract 2562 Objective: Clinical competence and practice performance among clinicians are difficult to measure. Self-assessments, while subjective, may determine gaps in knowledge and competence that affect performance. To determine the current knowledge level, competence, and clinical practices in diagnosing and managing iron overload (IO), an international survey was conducted among clinicians participating in the European School of Haematology (ESH) Iron Metabolism & Related Disorders Curriculum on the ESH website. Methods: An online survey was sent to 1197 participants in the ESH Curriculum to self-assess their level of competence and clinical practices in IO and its treatment in patients with myelodysplastic syndromes, thalassemia, sickle cell disease, hereditary hemochromatosis, and rare anemias. Results: Seventy-three of the 1197 participants responded to the survey, showing interest in the topic. Sixty-three (86.3%) were physicians, the majority of whom were hematologists (49.3%) or pediatric oncologists/pediatric hematologic oncologists (21.9%). Although 66.7% stated they always screen patients at risk for IO, only 50% said they always institute early iron chelation therapy (ICT) in patients with IO. While 73.4% of respondents stated they always instruct patients on the importance of adherence to ICT, only 58.5% always monitor their patients for adherence. Similarly, 60.9% of respondents stated that they always monitor patients for change in status and treatment response to ensure optimal dosing, but only 37.3% consider titration of ICT to reduce or maintain iron levels. Respondents were especially interested in further information on methods for monitoring iron load (77.6%), clinical guidelines for treatment of IO (74.6%), effect of IO on cardiac function/toxicity (67.2%), early identification of patients at risk for IO (65.7%), efficacy/safety of oral ICT (61.2%), and safety issues as they relate to IO treatment (61.2%). By self-assessment, 64.4% of the survey responders rated their current level of competence as high/very high regarding their ability to diagnose IO, evaluate techniques for assessing tissue iron levels, and interpret the findings; 70.2% also rated their ability to assess which patients were at risk of IO, the organs affected by IO, and the clinical sequelae/disease burden of IO as high/very high. Although 70.3% rated their ability to describe the rationale for using ICT and the mechanisms of action of various ICTs as high/very high, only 62.5% felt an equivalent ability to differentiate across various ICTs regarding their efficacy/safety, frequency/methods of administration, and approved indications for specific patient populations. More than 80% rated their desired level of competence as high/very high in terms of the ability to diagnose IO, assess tissue IO, and interpret the findings (84.0%); the ability to assess patients at risk for IO (89.4%); the rationale for using ICTs and the mechanisms of action of various ICTs (87.3%); and, most important, the ability to differentiate across ICTs regarding efficacy and safety, administration, and approved indications in specific populations (93.5%). The gaps between current level of competence and desired level of competence signal a need for continuous education on this topic. Conclusions: The survey points out significant gaps between clinicians' self-assessed levels of knowledge and competence in diagnosing and managing IO and implementation of this knowledge into practice. This was particularly evident in the gap between clinicians' desired level of competence in differentiating between various ICTs and their current level of competence in this area. The gaps uncovered in this survey highlight the fact that continuous educational reinforcement is critical for information to be incorporated into practice. The response rate to the survey among clinicians currently participating in an iron metabolism curriculum demonstrates their strong interest in these programs and their desire for continuing education in the areas identified. Disclosures: Cappellini: Novartis Pharmaceuticals Corporation: Consultancy, Speakers Bureau. Beris:Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Vifor International: Consultancy. Brissot:Novartis Pharmaceuticals Corporation: Research Funding, Speakers Bureau. Porter:Novartis Pharmaceuticals Corporation: Consultancy, Research Funding, Speakers Bureau; Genzyme Corporation: Consultancy; Resonance Health Ltd: Consultancy. Taher:Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
38
Serna, Laura Isabel. "Anita Maris Boggs." Feminist Media Histories 1, no. 2 (2015): 135–43. http://dx.doi.org/10.1525/fmh.2015.1.2.135.
Full textAbstract:
This short essay sketches the career of Anita Uada Maris Boggs, cofounder of the Bureau of Commercial Education, a charitable organization that from the 1910s through the 1930s circulated a library of sponsored films. I argue that Boggs's absence from film historiography has been doubly determined: first by the relative invisibility of educational film, and second by ideologies of gender that obscured women's work in the film industry, broadly construed, behind that of their male collaborators.
39
Straus, David J., Monika Dlugosz-Danecka, Joseph M. Connors, Árpád Illés, Marco Picardi, Ewa Lech-Marańda, Tatyana Feldman, et al. "Brentuximab Vedotin with Chemotherapy for Patients with Previously Untreated, Stage III/IV Classical Hodgkin Lymphoma: 5-Year Update of the ECHELON-1 Study." Blood 136, Supplement 1 (November 5, 2020): 26–28. http://dx.doi.org/10.1182/blood-2020-137089.
Full textAbstract:
Introduction Historically, nearly all relapses in classical Hodgkin lymphoma (cHL) occur within the first 5 years (Radford et al, BMJ 1997). In the phase 3 ECHELON-1 study (NCT01712490), treatment with brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) significantly improved modified progression-free survival (PFS) in patients (pts) with newly-diagnosed Stage III/IV cHL compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) (Connors et al, NEJM 2018). 3- and 4-year follow-up (Straus et al, Blood 2020; Bartlett et al, Blood 2019) reported durable PFS benefit with A+AVD vs ABVD in the intent-to-treat (ITT) population that was consistent across most key pt subgroups, irrespective of interim positron emission tomography (PET) scan status, disease stage, and baseline disease risk factor score. We report updated efficacy and safety results for pts in the ECHELON-1 study after a median follow-up of 55.6 months. Methods In this evaluation of longer follow-up, an exploratory analysis of PFS (time from randomization to relapse, progression, or death from any cause) per investigator (INV) was conducted, with a cutoff date of May 18, 2020. Pts with previously untreated Stage III or IV cHL were randomized 1:1 to receive up to six cycles of A+AVD (n=664) or ABVD (n=670) intravenously on days 1 and 15 of a 28-day cycle. An interim PET scan after cycle 2 (PET2) was required. Resolution and improvement (defined as improvement by ≥1 grade from worst grade as of the latest assessment) of peripheral neuropathy (PN) in pts with ongoing symptoms at the end of treatment (EoT) were monitored during the extended follow-up period. The rate of secondary malignancies, and the incidence and outcomes of pregnancies among pts and their partners were also assessed. Results With extended follow-up (median 55.6 months; 95% CI 55.2-56.7) estimated 5-year PFS rates were 82.0% (95% CI 78.7-84.8) for A+AVD and 75.2% (95% CI 71.5-78.4) for ABVD. Overall, PFS per INV favored A+AVD over ABVD (HR 0.691; 95% CI 0.543-0.880; p=0.003) (Table). Exploratory subgroup analyses by PET2 status and age demonstrated PFS benefits regardless of PET2 status (Table); estimated 5-year PFS per INV with A+AVD vs ABVD in the ITT population was 84.7% vs 78.8% in PET2-negative pts (HR 0.676; 95% CI 0.512-0.892; p=0.005), and 60.6% vs 45.9% in PET2-positive pts (HR 0.703; 95% CI 0.393-1.256; p=0.230). PFS benefit with A+AVD over ABVD was also independent of the number of International Prognostic Factors Project (IPFP) risk factors (Figure). After a median follow-up of almost 5-years, 84% (370/442) and 86% (245/286) of pts with treatment-emergent PN reported complete resolution or improvement of symptoms in the A+AVD and ABVD arms, respectively. Median time to complete resolution of PN events that were ongoing at EoT was 30 weeks (range 0-262) in the A+AVD arm and 16 weeks (range 0-267) in the ABVD arm; median time to improvement was 49 weeks (range 8-270) and 12 weeks (range 2-70) , respectively. Of the 132 (30%) pts with ongoing PN in the A+AVD arm, 77 (17%), 39 (9%), 15 (3%) and 1 (<1%) experienced a maximum severity of grade 1, 2, 3 or 4, respectively. In the ABVD arm, PN was ongoing in 61 pts (21%); maximum severity was grade 1, 2, 3 or 4 in 40 (14%), 17 (6%), 4 (1%) and 0 pts, respectively. A total of 124 pregnancies were reported among pts and their partners (40 female and 30 male pts in the A+AVD arm; 26 female and 28 male pts in the ABVD arm). The proportion of live births was similar between arms for female pts (26/40 in the A+AVD arm and 17/26 in the ABVD arm, 65% in each arm) and for male pts' partners (19/30 [63%] in the A+AVD arm and 20/28 [71%] in the ABVD arm). No stillbirths were recorded. Additional follow-up at an estimated median of ~5 years and secondary malignancy data will be presented. Conclusions After a median follow-up of 55.6 months, A+AVD continues to demonstrate a robust and durable treatment benefit independent of disease stage, risk factor score, and PET2 status. In addition, compared with ABVD, treatment adaptation by interim PET2 status is not required and bleomycin exposure is avoided. The sustained PFS benefit with A+AVD is coupled with a manageable safety profile with symptoms of PN improving or resolving over time and similar pregnancy rates in both treatment arms. The benefits observed with A+AVD at this important milestone suggest that A+AVD is an attractive treatment option for all pts with previously untreated Stage III or IV cHL. Disclosures Straus: Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees; Imedex, Inc.: Speakers Bureau; Targeted Oncology: Consultancy, Speakers Bureau; NY Lymphoma Rounds: Consultancy; Takeda Pharmaceuticals: Research Funding, Speakers Bureau; OncLive: Speakers Bureau; Elsevier: Membership on an entity's Board of Directors or advisory committees, Other: CME writer; ASH: Other: Conference in December 2019 on HL to other physicians during ASH; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Connors:Seattle Genetics: Other: Sponsorship to educational presentations; Takeda: Other: Sponsorship to educational presentations. Illés:Takeda, Seattle Genetics: Research Funding; Novartis, Janssen, Pfizer, Roche;: Other: Travel, Accommodations, Expenses; Janssen, Celgene, Takeda, Novartis Pharma SAS, Pfizer Pharmaceuticals Israel, Roche;: Consultancy, Honoraria; Celgene, Janssen, Novartis,Roche, Takeda: Consultancy. Lech-Marańda:Roche, Novartis, Takeda, Janssen-Cilag, Amgen, Gilead, AbbVie, Sanofi: Consultancy; Roche, Amgen, Gilead: Speakers Bureau. Feldman:KITE: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Morphosis: Other: Ad board; AstraZeneca: Other: Ad board; BMS/Celgene: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics: Consultancy, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Pharmacyclics: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. Smolewski:Roche Poland: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Sandoz: Honoraria; Morphosis: Honoraria. Savage:Roche (institutional): Research Funding; Merck, BMS, Seattle Genetics, Gilead, AstraZeneca, AbbVie, Servier: Consultancy; BeiGene: Other: Steering Committee; Merck, BMS, Seattle Genetics, Gilead, AstraZeneca, AbbVie: Honoraria. Bartlett:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Consultancy, Research Funding; Roche/Genentech: Consultancy, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; BTG: Consultancy; Acerta: Consultancy; Affimed Therapeutics: Research Funding; ADC Therapeutics: Consultancy; Autolus: Research Funding; BMS/Celgene: Research Funding; Forty Seven: Research Funding; Immune Design: Research Funding; Janssen: Research Funding; Kite, a Gilead Company: Research Funding; Merck: Research Funding; Millennium: Research Funding. Walewski:Gilead: Consultancy, Honoraria; Servier: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Other: Travel Support, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; GSK: Research Funding. Ramchandren:Janssen: Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding. Zinzani:Eusapharma: Consultancy, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics, Inc.: Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hutchings:Celgene, Genmab, Janssen, Novartis, F. Hoffmann-La Roche, Takeda: Research Funding; Genmab, F. Hoffmann-La Roche, Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Munoz:Juno/Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; Alexion: Consultancy; Beigene: Consultancy, Speakers Bureau; Fosunkite: Consultancy; Innovent: Consultancy; Acrotech/Aurobindo: Speakers Bureau; Verastem: Speakers Bureau; AstraZeneca: Speakers Bureau; Kyowa: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genentech/Roche: Research Funding, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; Merck: Research Funding; Portola: Research Funding; Incyte: Research Funding; Millenium: Research Funding; Pfizer: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau. Kim:JJ: Research Funding; Celltrion: Research Funding; Kyowa Kirn: Research Funding; Donga: Research Funding; Mundipharma: Research Funding; Pfizer: Research Funding; F. Hoffmann-La Roche: Research Funding. Advani:Astra Zeneca, Bayer Healthcare Pharmaceuticals, Cell Medica, Celgene, Genentech/Roche, Gilead, KitePharma, Kyowa, Portola Pharmaceuticals, Sanofi, Seattle Genetics, Takeda: Consultancy; Celgene, Forty Seven, Inc., Genentech/Roche, Janssen Pharmaceutical, Kura, Merck, Millenium, Pharmacyclics, Regeneron, Seattle Genetics: Research Funding. Ansell:Bristol Myers Squibb: Research Funding; Takeda: Research Funding; ADC Therapeutics: Research Funding; AI Therapeutics: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding. Younes:HCM: Consultancy; Daiichi Sankyo: Consultancy; Curis: Consultancy; BMS: Consultancy; Novartis: Consultancy; Epizyme: Consultancy; BioPath: Consultancy; AstraZeneca: Current Employment; Janssen: Consultancy; Takeda: Consultancy. Gallamini:Takeda: Other: Speaker. Liu:Takeda Pharmaceuticals: Current Employment. Little:Takeda: Current Employment, Current equity holder in publicly-traded company. Fenton:Seattle Genetics: Current Employment, Current equity holder in publicly-traded company. Fanale:Seattle Genetics: Current Employment, Current equity holder in publicly-traded company. Radford:GlaxoSmithKline: Current equity holder in publicly-traded company, Other: Spouse; AstraZeneca: Current equity holder in publicly-traded company, Other: Spouse; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Research Funding; ADCT: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
40
Maaba, Brown Bavusile. "Lost and found." Journal of the South African Society of Archivists 53 (December 16, 2020): 80–89. http://dx.doi.org/10.4314/jsasa.v53i1.6.
Full textAbstract:
In this paper, the author demonstrates that there is a range of primary sources on the Human Sciences Research Council (HSRC), South Africa’s foremost non-teaching social science research body and its predecessor, the South African National Bureau for Educational and Social Research, lodged in the country’s conventional and unconventional archives. The Central Records Department at Wits University is an example of the latter. Initially, scholars believed that the bulk of primary sources on the institution were not available. This has greatly affected the writing of the institution’s history and as a result it remains largely undocumented. This paper demonstrates that raw material on the institution can be and has been located through systematic research in various depositories around South Africa. The paper gives an overview of materials on the institution lodged in different archives and describes typical examples. Such primary sources can greatly assist scholars with a research interest in the HSRC and its predecessor, the Bureau.
41
Lai, Manhong, and Lijia Wang. "Fulfilling Set Objectives: A Case Study of Teacher Development in Two Primary Schools in Beijing." ECNU Review of Education 2, no. 2 (June 2019): 178–95. http://dx.doi.org/10.1177/2096531119853083.
Full textAbstract:
Purpose: This study aims to reveal the recent characteristics of school-based teacher development (STD) in China since it is perceived as a key measure to achieve success in raising educational quality in the country. Design/Approach/Methods: A qualitative research approach with in-depth interviews of 18 teachers at two primary schools in Beijing was used. Findings: Through the lens of cultural-historical activity theory (CHAT), it was observed that the objectives adaptation of teacher communities was made under the control of the District Education Bureau. STD provides the venue for ordinary teachers to learn, understand, and implement the teaching initiatives promoted by the district. Teacher communities at school level therefore implement continuous professional development initiatives promoted by Education Bureau teaching research officers. Originality/Value: This article argues that the administrative style of local government affected teacher community’s object, rules, and division of labor. It also contributes an indigenous interpretation of the CHAT theory.
42
Coffey, Margaret. "Project J-Hawk: Leadership in English Language Teacher Education." Issues in Language Instruction 5 (January 10, 2018): 8. http://dx.doi.org/10.17161/ili.v5i0.7011.
Full textAbstract:
The University of Kansas (KU) Applied English Center (AEC) has twice been awarded a U.S. Department of State grant to host a program for Vietnamese high school teachers in 2014-15 (Cohort 1) and 2015-16 (Cohort 2). Each cohort had 13 teachers from gifted high schools, many in underserved provinces that have substantial ethnic minority populations. Officially titled the English Language and Teacher Education Program for Vietnamese Teachers of Gifted Students (VNTP), the program is commonly referred to as Project JHawk. It is sponsored by the U.S. Department of State Bureau of Educational and Cultural Affairs and administered by the U.S. Department of State – Hanoi Bureau. The idea for the program grew out of a connection made by former KU AEC Language Specialist Kellie Smith Herrod with U.S. Embassy Public Affairs Officer Michael Turner while Smith Herrod was in Vietnam as a Fulbright Scholar (2013-2014). Thanks to Turner’s vision and heroic efforts, this unique program was created.
43
Coffey, Margaret. "Project J-Hawk: Leadership in English Language Teacher Education." Issues in Language Instruction 5, no. 1 (January 10, 2018): 8–14. http://dx.doi.org/10.17161/ili.v5i1.7011.
Full textAbstract:
The University of Kansas (KU) Applied English Center (AEC) has twice been awarded a U.S. Department of State grant to host a program for Vietnamese high school teachers in 2014-15 (Cohort 1) and 2015-16 (Cohort 2). Each cohort had 13 teachers from gifted high schools, many in underserved provinces that have substantial ethnic minority populations. Officially titled the English Language and Teacher Education Program for Vietnamese Teachers of Gifted Students (VNTP), the program is commonly referred to as Project JHawk. It is sponsored by the U.S. Department of State Bureau of Educational and Cultural Affairs and administered by the U.S. Department of State – Hanoi Bureau. The idea for the program grew out of a connection made by former KU AEC Language Specialist Kellie Smith Herrod with U.S. Embassy Public Affairs Officer Michael Turner while Smith Herrod was in Vietnam as a Fulbright Scholar (2013-2014). Thanks to Turner’s vision and heroic efforts, this unique program was created.
44
Kreuter, M., F. Bonella, G. Riemekasten, U. Müller-Ladner, J. Henes, E. Siegert, C. Guenther, et al. "AB0584 DOES ANTI-ACID TREATMENT INFLUENCE DISEASE PROGRESSION IN SYSTEMIC SCLEROSIS INTERSTITIAL LUNG DISEASE (SSC-ILD)? DATA FROM THE GERMAN SSC-NETWORK." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1589. http://dx.doi.org/10.1136/annrheumdis-2020-eular.3069.
Full textAbstract:
Background:Gastroesophageal reflux (GER) is common in SSc and thus treatment with anti-acid therapy (AAT) is frequent. An association between GER and the development / progression of SSc-ILD has been hypothesized. However, outcomes of AAT on disease progression in SSc-ILD has only sparsely been studied.Objectives:Methods:The German Network for Systemic Scleroderma (DNSS), which includes SSc pts. prospectively, was analyzed for SSc-ILD. Those without progression at ILD 1stdiagnosis were categorized in AAT vs. no-AAT users and disease outcome was assessed.Results:SSc-ILD was reported in 1165 (28.2%) out of 4131 pts. 712 of SSc-ILD pts had no disease progression at ILD 1stdiagnosis. 567 used AAT while 145 did not. Baseline characteristics were similar between groups with regards to age (mean 54.7 years), BMI, time since SSc diagnosis and immunosuppressant use. Significant differences in no-AAT vs. AAT were found for gender (male 18% vs. 25%, p=0.05), SSc subtype (p=0.002, diffuse more common in AAT), lung function (DLCO 66% vs. 58%, p=0.001; FVC 86% vs. 77%, p=0.001), mRSS (8 vs. 11.5, p<0.01), esophageal involvement (32% vs. 56%, p<0.01) and steroid use (30% vs. 43%, p=0.005). While mortality did not differ between groups (3.9%, p= 0.59), disease progression was more common in the AAT group than in no-AAT users (24.5% vs. 13%, p=0.03). Furthermore, there was a significant difference in decline of FVC≥10% with 30% in the AAT compared to 14% in no-AAT (p=0.018); a decline in DLCO≥15% was more common in the AAT group by trend (23% vs. 14%, p=0.087).Conclusion:While results may have partially been biased by differences in baseline characteristics, this current analysis disfavors the approach of AAT use for SSc-ILD.Disclosure of Interests:Michael Kreuter Grant/research support from: Roche, Boehringer, Consultant of: Roche, Boehringer, Speakers bureau: Boehringer, Roche, Francesco Bonella Grant/research support from: Boehringer, Consultant of: Boehringer, Roche, Bristol MS, Galapagos, Speakers bureau: Boehringer, Roche, Gabriela Riemekasten Consultant of: Cell Trend GmbH, Janssen, Actelion, Boehringer Ingelheim, Speakers bureau: Actelion, Novartis, Janssen, Roche, GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Ulf Müller-Ladner Speakers bureau: Biogen, Jörg Henes Grant/research support from: Novartis, Roche-Chugai, Consultant of: Novartis, Roche, Celgene, Pfizer, Abbvie, Sanofi, Boehringer-Ingelheim,, Elise Siegert Grant/research support from: Actelion, Consultant of: AEC, Speakers bureau: NA, Claudia Guenther: None declared, Ina Koetter Grant/research support from: Novartis, Roche, Speakers bureau: Abbvie, Actelion, Celgene, MSD, UCB, Sanofi, Lilly, Pfizer, Novartis, Chugai, Roche, Boehringer, Norbert Blank Speakers bureau: Actelion, Roche, Boehringer, Pfizer, Chugai, Christiane Pfeiffer: None declared, Marc Schmalzing: None declared, Gabriele Zeidler: None declared, PETER KORSTEN Grant/research support from: Novartis, Juarms GmbH, Consultant of: Abbvie, Pfizer, Lilly, BMS, Speakers bureau: Abbvie, Pfizer, chugai, BMS, Lilly, Sanofi aventis, Laura Susok: None declared, Aaron Juche: None declared, Margitta Worm Consultant of: Mylan Gemany, Bencard Allergie, BBV Technologies S.A., Novartis, Biotest, Sanofi, Aimmune Therapies, Regeneron, Speakers bureau: ALK-Abello, Novartis, Sanofi, Biotest, Mylan, Actelion, HAL Allergie, Aimmune Bencard Allergie, Ilona Jandova: None declared, Jan Ehrchen: None declared, Cord Sunderkoetter: None declared, Gernot Keyszer: None declared, Andreas Ramming Grant/research support from: Pfizer, Novartis, Consultant of: Boehringer Ingelheim, Novartis, Gilead, Pfizer, Speakers bureau: Boehringer Ingelheim, Roche, Janssen, Tim Schmeiser Speakers bureau: Actelion, UCB, Pfizer, Alexander Kreuter Speakers bureau: Sanofi, Abbvie, Merck Sharp&Dohme, Boehringer, Kathrin Kuhr: None declared, Hanns-Martin Lorenz Grant/research support from: Consultancy and/or speaker fees and/or travel reimbursements: Abbvie, MSD, BMS, Pfizer, Celgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, Astra-Zeneca, Lilly. Scientific support and/or educational seminars and/or clinical studies: Abbvie, MSD, BMS, Pfizer, Celgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, Astra-Zeneca, Lilly, Baxter, SOBI, Biogen, Actelion, Bayer Vital, Shire, Octapharm, Sanofi, Hexal, Mundipharm, Thermo Fisher., Consultant of: see above, Pia Moinzadeh: None declared, Nicolas Hunzelmann Speakers bureau: Actelion, Boehringer
45
Aguirre, Provilyn M., and Carlos Eduardo I. Legaspi. "Predictors of Academic Performance of Public Elementary School Learners." Philippine Social Science Journal 3, no. 2 (November 12, 2020): 63–64. http://dx.doi.org/10.52006/main.v3i2.267.
Full textAbstract:
Academic performance determines the quality and standard of efficiency and effectiveness of an educational system. The Research Forum Presentation Philippines' Approach to Assessment of the 21st Century Skills Assessment Curriculum and Technology Research Center (ACTRC) stressed that learners need to acquire 21st-century skills. To address this concern, the Philippines, through its educational agencies, including the Department of Education (DepEd) for the elementary school learners, has merged the learning approach in developing the 21st-century skills through the K to12 education reform agenda. Through its Bureau of Educational Assessment, DepEd has worked to define the skills and determine the opportunities of public elementary school learners of Bacolod City during the School Year 2019-2020. Likewise, it explores the relationship between the predictors of learners' academic performance using the demographic, such as age, sex, birth order, family living condition, monthly family income, nutritional status, and the level of academic performance of the learners in a public elementary school.
46
Drummond, Mark W., Charlotte Gaskell, Claire Harrison, Adam J. Mead, Christina Yap, Aimee E. Jackson, Jennifer Byrne, et al. "Phazar: A Phase Ib Study to Assess the Safety and Tolerability of Ruxolitinib in Combination with Azacitidine in Advanced Phase Myeloproliferative Neoplasms (MPN), Including Myelodysplastic Syndromes (MDS) or Acute Myeloid Leukaemia (AML) Arising from MPN [ISRCTN16783472]." Blood 136, Supplement 1 (November 5, 2020): 2–3. http://dx.doi.org/10.1182/blood-2020-138437.
Full textAbstract:
Background Treatments for 'accelerated phase' MPNs (MPN-AP, 10-19% blasts)/post-MPN AML (MPN-BP, ≥20% blasts) are limited. Most patients are precluded from potentially curative haematopoietic stem cell transplantation (HSCT). For HSCT ineligible patients, azacitidine (AZA) is licensed to treat high-risk MDS or AML. Whilst dose and toxicity profile of AZA is well understood, the response of MPNs and post-MPN AML to monotherapy is limited. AZA-based doublet chemotherapy may however result in improved clinical responses. The phase Ib single-arm PHAZAR trial was established to determine maximum tolerated dose (MTD), safety profile and clinical activity of the selective JAK1/2 inhibitor ruxolitinib (RUX) used in combination with AZA to treat MPN-AP and MPN-BP patients. Methods A modified two-stage continual reassessment method with an expansion cohort at the MTD, was used to establish the MTD of RUX in combination with AZA. Successive flexible cohorts of 3-5 patients were enrolled at a fixed AZA dose of 75 mg/m2 s/c for 7 days (excluding weekends, on a 5-2-2 schedule) of a 28-day cycle with continuous administration of an allocated oral RUX dose (dose levels 0, 1, 2 and 3 = 10, 15, 20 and 25 mg BD respectively), and a formal response assessment recorded after 6 cycles. Toxicities were prospectively recorded as per CTCAE v4.0 with dose limiting toxicity (DLT) defined as a grade 3 or 4 non-haematological toxicity during treatment cycle 1. Clinical activity was evaluated over 12 months through assessment of bone marrow response after 3 and 6 treatment cycles, progression free survival (PFS), leukaemia free survival (LFS) and overall survival (OS). Results Thirty four advanced phase MPN patients were recruited from 12 Trials Acceleration Programme sites (19 MPN-AP; 15 MPN-BP). Baseline characteristics are summarized in Table 1. Driver mutation status was available for 25/34(74%) patients. 17/25(68%) carried canonical mutations in JAK2, 4/25 (16%) in CALR, and 4/25(16%) were triple negative. Three patients each received 10 and 15 mg of RUX BD, 4 patients received 20 mg RUX BD, 21 patients received 25 mg RUX BD and 3 did not begin treatment. Median number of cycles received was 3 RUX and 4 AZA. The MTD of RUX in combination with AZA was determined at 25 mg BD, with no DLTs reported during phase 1 of the study. During the expansion phase, 1 DLT at dose level 3 was reported as grade 3 febrile neutropenia; with this patient's RUX dose reduced from 25 to 20 mg BD. Overall, 601 adverse events were reported of which 16.3% were grade 3 and 3.5% grade 4, with anaemia and febrile neutropenia the most common grade 3 and 4 events. There were 77 serious adverse events reported with 50.6% believed trial treatment related; febrile neutropenia, sepsis and, infections and infestations were the most common affecting 29.4%, 14.7% and 14.7% of patients respectively. In total, 20 of 34 patients were evaluable for disease response. IWG MDS criteria were used for blasts <20% at baseline (Cheson Blood 2006), and Post MPN AML Consortium criteria for blasts ≥20% (Mascarenhas Leuk Res 2012). After 3 and 6 cycles the best responses achieved by MPN-AP patients were, 1 complete remission (CR), 4 marrow CR, 1 partial remission, 4 stable disease (SD), and 3 progressive disease. Best responses achieved by MPN-BP patients were, 4 acute leukaemia response-partial and 3 SD. The median response duration was 322 days for MPN-AP and 199 days for MPN-BP patients. Of the 14 RBC transfusion dependent patients at baseline, 0 and 3 (21.4%) of these achieved RBC transfusion independence after 3 and 6 cycles respectively. At baseline 7 patients were platelet transfusion dependent, 4 (57.1%) of these patients achieved platelet transfusion independence after 3 cycles and 1 (14.3%) persisted through 6 cycles. At 12 months the median PFS was 42.1% (95% CI: 17.9, 64.7), LFS was 26.4% (95% CI: 6.5, 52.2) and OS was 42.4% (95% CI: 23.8, 59.8). Conclusions The combination of RUX and AZA is well tolerated in MPN-AP and MPN-BP patients with toxicities comparable to the individual agents. Of evaluable patients 10 of 20 achieved a PR or CR. The OS compares favourably with historical cohorts and clinically meaningful responses were achieved for transfusion independence. In 1 patient the regimen permitted successful bridge to transplant. Such combinations should be further explored, potentially with higher dose RUX. An expanded molecular analysis including responses is presented as a separate abstract. Disclosures Drummond: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Blueprint Medicine Corporation: Research Funding; Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astellas: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Harrison:Shire: Honoraria, Speakers Bureau; Gilead Sciences: Honoraria, Speakers Bureau; Incyte Corporation: Speakers Bureau; Promedior: Honoraria; AOP Orphan Pharmaceuticals: Honoraria; CTI Biopharma Corp: Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; Sierra Oncology: Honoraria; Roche: Honoraria; Janssen: Speakers Bureau. Mead:Celgene/BMS: Consultancy, Honoraria, Other: travel, accommodations, expenses, Research Funding; Novartis: Consultancy, Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau; Gilead: Consultancy; CTI: Consultancy; Abbvie: Consultancy. Yap:Bristol-Myers Squibb: Honoraria, Speakers Bureau; Faron Pharmaceuticals: Consultancy. Narayanan:Takeda: Other: Educational support to attend conferences; Alexion: Speakers Bureau; MSD: Speakers Bureau; Celgene: Other: Educational support to attend conferences; Novartis: Other: Educational support to attend conferences. Somervaille:Novartis: Consultancy, Honoraria; Imago Bioscience: Research Funding. Gudgin:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Milojkovic:Incyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria. Knapper:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. OffLabel Disclosure: 5-azacitidine is licensed and approved for treatment of adult patients who are not eligible for HSCT with high risk myelodyplastic syndromes. Ruxolitinib is licensed and approved for use in Myelofibrosis and for Polycythaemia Vera resistant/intolerant to hydroxyurea
47
Fleisch, Brahm David. "Social scientists as policy makers: E. G. Malherbe and the national bureau for educational and social research, 1929–1943." Journal of Southern African Studies 21, no. 3 (September 1995): 349–72. http://dx.doi.org/10.1080/03057079508708452.
Full text
48
Kumar, Dheeraj. "A Study on University Grant Commission Educational Testing Bureau (UGC-NET) Library and Information Science Result (June 2012–15)." Pearl : A Journal of Library and Information Science 10, no. 3 (2016): 167. http://dx.doi.org/10.5958/0975-6922.2016.00023.1.
Full text
49
Taylor, Bryan C., Lee P. Shulman, Malcolm G. Munro, Stephanie Martin, Anita L. Nelson, and Patricia A. Locantore-Ford. "Advancing OB/GYN Knowledge, Competence, and Performance Related to Abnormal Uterine Bleeding and Intravenous Iron Supplementation for Effective Management of Iron Deficiency Anemia: Outcomes Analysis from a 2019 Educational Initiative." Blood 136, Supplement 1 (November 5, 2020): 28–29. http://dx.doi.org/10.1182/blood-2020-133836.
Full textAbstract:
Background: Iron deficiency anemia (IDA) is a multifaceted condition associated with immense obstetrical morbidity and mortality, and is especially prevalent in female patients of reproductive age.Abnormal uterine bleeding (AUB), which often manifests clinically as heavy menstrual bleeding (HMB), is the leading cause of IDA among reproductive age women in the United States, with a prevalence ranging from ~30-50% in this patient population; further, HMB is estimated to account for nearly one-third of all IDA causes worldwide. For these reasons, AUB/HMB is generally accepted as the primary causal source of IDA in daily clinical practice.As frontline clinicians who routinely manage HMB, OB/GYNs are optimally positioned to subsequently recognize, diagnose, and treat the IDA precipitated by HMB. However, to ensure the provision of safe and effective care, adaptive educational initiatives with an emphasis on evolving iron supplementation strategies are needed. Methods: Creative Educational Concepts (CEC) conducted a literature review, needs assessment, and detailed gap analysis to identify prominent clinical and educational gaps that exist among OB/GYNs with regard to IDA sign and symptom recognition, epidemiology, clinical gravity and risk factors, formal diagnosis, and appropriate treatment.Consequently, our team at CEC composed a responsive, multi-pronged educational design targeted to obstetricians, gynecologists, and women's health professionals, in a tailored effort to bridge the aforementioned gaps in current practice and improve outcomes for patients.CEC consulted with top experts in obstetrics and gynecology, maternal fetal medicine, pelvic surgery, and hematology at every stage of the educational design and delivery continuum, from proposal ideation to content development to live, on-site presentation.To dynamically engage the target audience, especially at the community, grassroots level, this educational initiative was delivered at a series of five American College of Obstetricians and Gynecologists (ACOG) District Meetings across the United States; live meetings were held in Lake Geneva, WI; San Diego, CA; Kapalua, HI; Rockport, ME; and Manhattan, NY. Results: 203 total clinicians were educated across the initiative Profession MD/DO - 93%APRN/CNM - 3%RN - 2%Other - 2%Specialty General OB/GYN - 81%Maternal/fetal Medicine - 11%Reproductive endocrinology - 4%Pelvic medicine/surgery - 2%Other - 2%>5,000 IDA patients potentially impacted per month as a result of the initiativeStatistically significant advances in learning and knowledge were achieved from pre- to post-activity for all tested educational gaps: Identification of IDA risk factors (85% post vs. 46% pre; P<0.001)Clinical implications of AUB (95% post vs. 74% pre; P<0.001)Appropriate clinical utility of IV iron (93% post vs. 63% pre; P<0.001)Top intended practice changes: Consider IV iron supplementation in my patients with IDA for whom oral iron supplementation is ineffective or intolerableConsider IV iron supplementation as first-line treatment for my patients with severe IDA, ongoing bleeding, and/or absorption deficienciesShare information learned with colleagues and other members of my healthcare teamTop anticipated barriers to change: Limited experience with parenteral iron supplementation therapiesPatient non-adherenceInadequate care coordination between OB/GYNs and primary care physiciansGiven an HMB-associated IDA patient case, activity attendees demonstrated a significant retention of knowledge and clinical performance improvement from pre-test to 4-week follow-up related to appropriate initiation of IV iron 90% at 4-wk follow-up vs. 63% at pre-test (P=0.018) Conclusions: Our 2019 ACOG District Meeting educational initiative precipitated substantive practice advances in knowledge, competence, and performance among OB/GYNs and women's health professionals related to IDA management.Statistically significant performance improvements in appropriate initiation of IV iron for treatment of HMB-associated IDA were achieved at follow-up assessment.Learning and knowledge endpoints for IDA risk factor recognition and AUB clinical implications were not retained with statistical significance at follow-up assessment, thereby evidencing residual educational gaps and a need for ongoing education in this space. Disclosures Shulman: Bayer: Consultancy; AMAG: Speakers Bureau; Lupin: Speakers Bureau; Vermillion: Speakers Bureau. Munro:Vifor: Consultancy; Abbvie: Consultancy, Research Funding; American Regent: Consultancy; Boston Scientific: Consultancy; Daiichi Sankyo: Consultancy. Martin:Daiichi Sankyo: Consultancy. Nelson:Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AMAG: Consultancy; Agile Pharmaceutical: Consultancy, Research Funding; EvoFem: Research Funding; Sebela Pharmaceutica: Consultancy, Research Funding; TherapeuticsMD: Membership on an entity's Board of Directors or advisory committees; American Regent: Consultancy, Membership on an entity's Board of Directors or advisory committees.
50
Duell, Johannes, Kami J. Maddocks, Eva González-Barca, Wojciech Jurczak, Anna Marina Liberati, Sven de Vos, Zsolt Nagy, et al. "Subgroup Analyses from L-Mind, a Phase II Study of Tafasitamab (MOR208) Combined with Lenalidomide in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma." Blood 134, Supplement_1 (November 13, 2019): 1582. http://dx.doi.org/10.1182/blood-2019-122573.
Full textAbstract:
Introduction Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplant (ASCT) have a poor prognosis. Tafasitamab (MOR208) is an Fc-enhanced, humanized, monoclonal antibody that targets CD19, which is broadly expressed across B-cell malignancies, including DLBCL. Lenalidomide (LEN) is an immunomodulatory drug with antiproliferative and antiangiogenic effects. Combined tafasitamab + LEN has shown enhanced activity in in vitro and in vivo lymphoma models. L-MIND (NCT02399085) is an ongoing, open-label, single-arm, Phase II study of tafasitamab + LEN in patients with R/R DLBCL who are ineligible for ASCT. Here, we present results from prespecified patient subgroup analyses from L-MIND. Methods Patients aged ≥18 years with R/R DLBCL (1-3 prior systemic therapies, including ≥1 CD20-targeting regimen) with an Eastern Cooperative Oncology Group performance status 0-2, and who were ineligible for ASCT were enrolled. Patients received 28-day cycles of tafasitamab (12 mg/kg intravenously), once weekly during Cycles 1-3 with a loading dose on Cycle 1 Day 4, then every 2 weeks during Cycles 4-12. LEN (25 mg orally) was administered on Days 1-21 of Cycles 1-12. After Cycle 12, progression-free patients received tafasitamab every 2 weeks until disease progression. The primary endpoint is objective response rate (ORR; partial response [PR] + complete response [CR]), assessed centrally by an independent review committee (IRC) per International Working Group criteria 2007, incorporating PET-based imaging. Secondary endpoints include ORR (investigator-assessed), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety and biomarker analyses. Results Of 81 patients enrolled, 80 patients received tafasitamab + LEN and were included in the full analysis set (FAS) for efficacy (data cut-off 30 Nov 2018). Median follow-up was 17.3 months. In the FAS, ORR was 60.0% (95% confidence interval [CI]: 48.4-70.8) (Figure 1A). The CR rate was 42.5% (n=34/80), of which 88.2% (n=30/34) were PET-confirmed. Median time to response (PR or CR) was 2.0 months and median time to CR was 7.1 months. Median DOR was 21.7 months (95% CI: 21.7-not reached [NR]); median PFS was 12.1 months (95% CI: 5.7-NR); and median OS was NR (95% CI: 18.3-NR) with a median follow-up of 19.6 months. The 12-month DOR and OS rates were 71.6% (95% CI: 55.1-82.9) (Figure 1B) and 73.7% (95% CI: 62.2-82.2) (Figure 1C), respectively. In the subgroup analysis, patients with CR as best objective response (BOR) had better outcomes than those with PR: median DOR, NR (95% CI: 21.7-NR) vs 4.4 months (95% CI: 2.0-9.1); 12-month DOR rate, 93.2% (95% CI: 75.4-98.3) vs 14.4% (95% CI: 1.1-43.7); and 12-month OS rate, 97.1% vs 76.9%. Patients with one prior line of therapy had a trend for better outcomes than those with ≥2 prior lines: ORR, 70.0% vs 50.0%; and 12-month OS rate, 86.9% vs 60.1%. However, the 12-month DOR rate was similar regardless of the number of prior lines (one prior line: 70.5% [95% CI: 47.2-85.0] vs ≥2 prior lines: 72.7% [95% CI: 46.3-87.6]). For patients who were refractory to primary therapy or their last line of therapy, similar ORRs were observed to non-refractory patients (60.0% vs 60.0%); 12-month DOR was similar regardless of refractory status to last therapy; and 12-month OS rates were higher in non-refractory patients (Figure 1C). As expected, patients with a low/low-intermediate International Prognostic Index (IPI) score had better outcomes than those with an intermediate-high/high score: ORR, 70.0% vs 50.0%; 12-month DOR rate, 86.5% vs 50.4%; and 12-month OS rate, 87.0% vs 59.9%. Based on Hans algorithm, encouraging outcomes were reported in patients with germinal center B-cell (GCB) DLBCL (n=37), and outcomes were even better in those with non-GCB DLBCL (n=21): ORR, 48.6% vs 71.4%; median DOR, NR vs 21.7 months; 12-month DOR rate, 53.5% vs 83.1%; and 12-month OS rate, 65.4% vs 84.2%. Conclusions Tafasitamab + LEN combination followed by tafasitamab monotherapy shows encouraging activity with durable responses in ASCT-ineligible patients with R/R DLBCL. L-MIND includes a substantial number of poor prognosis patient subgroups. While the influence of these risk factors is evident, the clinical activity of tafasitamab + LEN in these difficult-to-treat patients is promising, particularly in those who were refractory to prior therapies. Disclosures Duell: Regeneron Pharmaceuticals, Inc.: Research Funding. Maddocks:Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Merck: Research Funding; BMS: Research Funding. González-Barca:Janssen: Consultancy, Honoraria; Kiowa: Consultancy; Celtrion: Consultancy; Celgene: Consultancy; AbbVie: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Takeda: Honoraria. Jurczak:TG Therapeutics: Research Funding; Roche: Research Funding; Takeda: Research Funding; Servier: Research Funding; Celtrion: Research Funding; Novo Nordisk: Research Funding; Incyte: Research Funding; Bayer: Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; MorphoSys: Research Funding. Liberati:Incyte: Consultancy; Janssen: Honoraria; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Bristol & Mayer: Honoraria. de Vos:Bayer: Consultancy; Verastem: Consultancy; Portola Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Nagy:Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Gaidano:AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sunesys: Consultancy, Honoraria; Astra-Zeneca: Consultancy, Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Abrisqueta:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, expenses, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel, Accommodations, expenses, Speakers Bureau; Abbvie: Consultancy, Honoraria, Other: Travel, Accommodations, expenses, Speakers Bureau. André:Takeda: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers-Squibb: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Other: Travel grants, Research Funding; Amgen: Other: Travel grants, Research Funding; Johnson & Johnson: Research Funding; Takeda Millenium: Research Funding; Chugai: Research Funding; Celgene: Other: Travel grants, Research Funding. Dreyling:Celgene: Other: Scientific advisory board, Research Funding, Speakers Bureau; Gilead: Other: Scientific advisory board, Speakers Bureau; Janssen: Other: Scientific advisory board, Research Funding, Speakers Bureau; Mundipharma: Other: Scientific advisory board, Research Funding; Novartis: Other: Scientific advisory board; Roche: Other: Scientific advisory board, Research Funding, Speakers Bureau; Sandoz: Other: Scientific advisory board; Acerta: Other: Scientific advisory board; Bayer: Other: Scientific advisory board, Speakers Bureau. Menne:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kite/Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant; Daiichi Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astra Zeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kyowa Kirin: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau. Dirnberger-Hertweck:MorphoSys: Employment. Weirather:MorphoSys: Employment. Ambarkhane:MorphoSys: Employment. Salles:Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Other: Educational events; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Epizyme: Consultancy, Honoraria; Novartis, Servier, AbbVie, Karyopharm, Kite, MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria.