1,721,037 research outputs found
Patient and disease precursors and clinical predictors of prolonged cytopenias in patients with aggressive B-cell non-Hodgkin's lymphoma treated with chimeric antigen receptor T-cell therapy
Full text linkINTRODUCTION: Chimeric antigen receptor (CAR) T-cell therapy is a new treatment for hematologic malignancies including aggressive B-cell non-Hodgkin’s lymphoma (NHL). Although it has provided an effective treatment option for patients who have few options, CAR T-cell therapy does have many associated toxicities. Prolonged cytopenias are one of the lesser understood toxicities that can affect upwards of 40% of patients.
METHODS: In this retrospective study, we reviewed 106 patients who received commercial CAR T-cell therapy between November 2017 and September 2019. Prolonged cytopenias were defined as having absolute neutrophil count (ANC) <1000/mm3, platelets (PLT) <50,000/mm3, and/or hemoglobin (Hgb) <10 g/dL at least once after 30 days post-CAR T-cell infusion. Furthermore, if only one incidence of cytopenia was recorded 30 days post infusion, we required that the patient had to have received either a transfusion or granulocyte-colony stimulating factor (GCSF) after the date of the recorded cytopenic value to be considered a part of the cytopenic cohort.
RESULTS: 22 patients met the criteria of having prolonged cytopenias. 64% of the cytopenic cohort had >1 type of prolonged cytopenias. Anemia was the most prevalent affecting 72% of cytopenic patients. The length of time from diagnosis of aggressive B-cell NHL to date of CAR T-cell infusion was found to be positively correlated with an increased risk of developing prolonged cytopenias following CAR T-cell therapy. Additional risk factors associated with an increased risk of delayed cytopenias by univariate analysis included neutropenia on the day of infusion (day 0), a high C-reactive protein (CRP) before lymphodepletion and on day 0, day 0 PLT count, and Hgb before lymphodepletion and on day 0. On multivariate analysis, only high CRP before lymphodepletion was associated with an increased risk of prolonged cytopenias while high ferritin and PLT values on day 0 were associated with not developing prolonged cytopenias. There was no statistical difference between the cytopenic and non-cytopenic cohorts in rates of progression free survival (PFS) and overall survival (OS). Also, no difference was seen in rates or severity of other toxicities between cohorts. 41% of the cytopenic cohort experienced infectious complications post-infusion with one patient dying from their infectious complications. However, there was no association with incidence of infection and prolonged cytopenias when compared to the incidence of infection in the non-cytopenic cohort.
CONCLUSIONS: A longer time from diagnosis of aggressive B-cell NHL to time of CAR T-cell infusion was associated with prolonged cytopenias while the number of lines of prior chemotherapy and rate of prior high dose chemotherapy with an autologous stem cell transplant (HD-ASCT) were not associated. It would be valuable to confirm this association and why it is associated since the other two factors were not. We lacked bone marrow biopsies before CAR T-cell infusion and did not have bone marrow biopsies for many patients after CAR T-cell infusion. It would be beneficial to collect data regarding bone marrow biopsies from these time points to highlight any changes that could be related to CAR T-cell therapy. Cytogenetic information of individual patient’s diseases would be worth analyzing to help determine if there are biological factors associated with prolonged cytopenias in response to CAR T-cell therapy. Additional studies should investigate the laboratory values we found to have associations with either cohort to help identify possible predictive values providers could use to identify patients at higher risk of having prolonged cytopenias. There is also a need to see if specific prior chemotherapy regimens increase a patient’s risk of having prolonged cytopenias. Overall, since prolonged cytopenias after CAR T-cell infusions have not been heavily investigated, further investigation is needed to better understand the predictive factors and identify possible mechanisms of prolonged cytopenias seen in CAR T-cell patients
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Early clinical and radiological predictors of relapse following partial response to chimeric antigen receptor T-cell therapy in patients with aggressive B-cell Non-Hodgkins lymphoma
Full text linkINTRODUCTION: Chimeric antigen receptor (CAR) T-cell therapy is a relatively new cancer immunotherapy that is offering remarkable benefits for patients in the third line setting for relapsed/refractory aggressive large B-cell non-Hodgkin’s lymphoma (NHL). At one-month restaging post CAR T-cell therapy, approximately 30% of patients are found to be in a partial response (PR) or to have stable disease (SD) to therapy, and these patients diverge into 30% who deepen into a complete response (CR) and the remaining 70% who ultimately progress (PD). To date there has been no way to predict who will enter remission and who will progress. Our study seeks to better understand these diverging patient groups and identify early predictive markers of progression. Patients projected to progress could then be treated with adjuvant therapies that could both kill residual tumor cells and improve residual CAR T-cell activation in order to increase the probability of a deepening of response.
METHODS: In this retrospective analysis, we evaluated 259 patients who were treated with anti-CD19 directed CAR T-cell therapy for r/r B-NHL at the Dana-Farber Cancer Institute between December 2017 and June 2021. Patients with a PR or SD at 1 month were further classified into two cohorts according to their subsequent response conversion. Those that are known to have progressed from their PR/SD were included in the PD cohort, and the rest of the PR/SD patients were included in the non-PD cohort. Early clinical and radiological parameters up to the 1 month restaging scan were included in our analysis.
RESULTS: The overall response rate for our patient sample was 79% with a best response of CR in 64% of patients. At 1 month restaging 52% of patients were in CR, 28% in PR, 2% SD, and 18% PD. Median follow-up was 9 months. 41% of patients deepened their response from PR/SD into a CR, 90% of whom remain in a CR to last follow-up, and 42% were known to have progressed. The PD cohort had poorer progression-free survival (3 months vs. 11 months) and overall survival (11 months vs. not yet reached) than the non- PD cohort. Parameters significantly correlated to progression included poor performance status; high CRP and low Hgb at Day -30; high CRP at lymphodepletion; need for early admission; low Hgb, high LDH, and high ferritin on Day 0; CRS Lee grade 2+ and low albumin at CRS onset; high ferritin at time of CRS treatment; and Deauville score of 5 on restaging scan. High MTV and TLG on pre- and post-infusion PET scans also trended with those who progressed.
CONCLUSIONS: The findings of our analysis that were correlated to progression are primarily related to poor lymphoma biology pre-therapy, residual lymphoma, and CRS onset kinetics. Notably, inflammatory markers and maximal CRS post-therapy were not significant. A primary difference between the two PR patient groups may thus relate to the tumor microenvironments pre-infusion with greater tumor bulk in the PD cohort possibly corresponding to tumor microenvironments that are more inflammatory and hostile to CAR T-cells. We therefore define a new prognostic scoring system, to be validated in future studies, that utilizes five early clinical parameters and establishes three risk groups with significantly different prognoses for PR/SD patients. Evaluation of post-infusion minimal residual disease, CD19 status, PD-L1 status, and other molecular markers could be useful in better understanding and differentiating the pathophysiologies characterizing these patient groups
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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