1,721,025 research outputs found
High Body Mass Index Is Associated with Favorable Outcome in Younger Patients Receiving CD19 CAR T-Cell Therapy for B-Cell Lymphoma: A Retrospective Study from the EBMT Transplant Complications Working Party
No full textIntroduction: Obesity is a major health care burden and has been linked to numerous adverse outcomes including alterations of antitumor immunologic responses. Patients with high body mass index (BMI) undergoing autologous or allogeneic hematopoietic stem cell transplantation (HSCT) for hematological malignancies were repeatedly shown to have higher rates of non-relapse mortality (NRM) and relapse, translating into a reduced overall survival (OS). However, the impact of obesity on outcomes after CAR T-cell therapy has not been studied at large scale. The present study aims to investigate whether high BMI is associated with outcomes in patients receiving anti-CD19 CAR T-cell therapy.
Methods: This is a retrospective analysis using EBMT registry data of adult patients after first therapy with commercial CD19 CAR T-cell products for relapsed/refractory B-Non-Hodgkin lymphoma (B-NHL) between 1/1/2016 and 30/6/2022. Only patients with available information on height and weight at CAR T-cell therapy were included. Patients with a history of allogeneic stem cell transplantation were excluded. As we exclusively focused on the impact of increased BMI we excluded all patients with a BMI below 18.5 from the analysis. The primary outcome was the impact of BMI on OS. Multivariate analyses were performed with cause-specific Cox models, employing as risk factors patient age, sex, ECOG status and year of CAR T-cell therapy besides BMI categories (18.5-25, 25-30, >30).
Results: A total of 4576 CAR T-cell therapy patients were registered during the study period, with 3125 patients meeting inclusion criteria. Selection of patients with available height and weight including BMI of 18.5 and above resulted in a final study cohort of 1653 patients. Median follow-up was 21.2 months [95% CI: 19.6-22.6]. Patients' characteristics are summarized in Table 1. Half of the cohort had a normal range BMI, while one third was overweight (BMI 25-30) and about 18% met criteria for obesity. A significant interaction was found between age and BMI. Therefore, we divided the cohort in two groups by the median age of 62.5 years. OS was significantly reduced in younger patients with normal range BMI compared to higher BMI patients. However, this effect was not significant in the older patients (Figure 1). Upon multivariate analysis, younger patients with BMI 25-30 had a survival advantage with a hazard ratio (HR) of 0.74 (0.57-0.95, P=0.02) and patients with BMI >30 a HR of 0.68 (0.51-0.91, P=0.01) compared to normal range BMI. Progression free survival was significantly improved for younger BMI 25-30 (HR 0.79, 0.64-0.99, P=0.04) but not BMI >30 (HR 0.82, 0.64-1.05, P=0.11), and NRM was reduced only in the younger BMI 25-30 subgroup (HR 0.52, 0.31-0.9, P=0.02) but not in the obese patients (HR 0.7, 0.42-1.18, P=0.19). Multivariate analysis of BMI subgroups in patients above the age of 62.5 years did not show significant differences with regard to OS (BMI 25-30 HR 0.94, 0.74-1.18; BMI >30 HR 1.04, 0.77-1.41), PFS (BMI 25-30 HR 1.06, 0.86-1.31; BMI >30 HR 1.1, 0.83-1.47), or NRM (BMI 25-30 HR 1.35, 0.89-2.06; BMI >30 HR 1.11, 0.6-2.06).
Conclusion: Our European real world data on the impact of increased BMI on anti-CD19 CAR T-cell therapy for relapsed/refractory B-NHL shows that half of these patients are overweight or obese and that this seems to confer a survival benefit to younger (<62.5 years) patients. As this finding is rather surprising, future studies are required to fine tune the risk analysis, including in-depth analysis of patients' characteristics to identify protective factors linked to an elevated BMI as well as a possible selection bias. Our findings could in part be explained by the body weight-dependent dose of infused CAR T-cells for B-cell lymphoma. Therefore, for the same tumor burden, obese patients might receive more CAR T-cells than normal weight ones. A future study should test this hypothesis also in B-ALL or multiple myeloma patients, as they typically receive a fixed dose of CAR T-cells regardless of their body weight. Ultimately, our study might contribute to identify underlying mechanisms for improved outcome of CAR T-cell patients
GVHD prophylaxis in matched related stem cell transplantation: Why post-transplant cyclophosphamide can be recommended a study by the EBMT transplant complications working party
No full textAbstract Rabbit anti-thymocyte globulin (rATG) reduced chronic GVHD after matched related donor (MRD) allogeneic stem cell transplantation (alloSCT) from 69% to 32% in a randomized trial and is the recommended standard in Europe. Post-transplantation Cyclophosphamide (PTCy) is an emerging alternative but lacks such solid data in MRD alloSCT. We therefore analyzed outcomes of rATG ( n = 4140) vs. PTCy ( n = 1069) in adult patients with hematologic malignancies undergoing MRD alloSCT between 2017 and 2021 in the EBMT database. The provided hazard ratios (HR) and P-values are adjusted for potential risk factors using multivariate analysis. Results are given at 2 years after alloSCT for all endpoints except for acute GVHD (100 days). The main difference was a lower relapse incidence after PTCy vs. rATG (26.2% vs. 32.8%; HR 0.78 [CI 95%: 0.66–0.92], p = 0.003). Interaction analyses confirmed the consistency of this result across different disease risk index and conditioning intensity subgroups. Other major transplant outcomes showed no significant differences: non-relapse mortality, overall survival, progression-free survival, GVHD-free relapse-free survival, incidence and severity of acute GVHD as well as chronic GVHD. In summary, PTCy results in comparable GVHD and survival outcomes but lower relapse rates compared to rATG. We conclude that PTCy can be recommended in MRD alloSCT
Organ complications after CD19 CAR T-cell therapy for large B cell lymphoma: a retrospective study from the EBMT transplant complications and lymphoma working party
No full textWe investigated ≥ grade 3 (CTC-AE) organ toxicities for commercial CD19 chimeric antigen receptor T cell (CAR-T cell) products in 492 patients (Axi-Cel; n = 315; Tisa-Cel; n = 177) with Large B-cell Lymphoma in the European Society for Blood and Marrow Transplantation (EBMT) CAR-T registry. The incidence of ≥ grade 3 organ toxicities during the first 100 days after CAR-T was low and the most frequent were: renal (3.0%), cardiac (2.3%), gastro-intestinal (2.3%) and hepatic (1.8%). The majority occurred within three weeks after CAR-T cell therapy. Overall survival was 83.1% [79.8-86.5; 95% CI] at 3 months and 53.5% [49-58.4; 95% CI] at one year after CAR-T. The most frequent cause of death was tumour progression (85.1%). Non-relapse mortality was 3.1% [2.3-4.1; 95% CI] at 3 months and 5.2% [4.1-6.5; 95% CI] at one year after CAR-T. The most frequent causes of non-relapse mortality were cell-therapy-related toxicities including organ toxicities (6.4% of total deaths) and infections (4.4% of total deaths). Our data demonstrates good safety in the European real-world setting
Organ Complications after CD19 CAR T-Cell Therapy for Large B Cell Lymphoma. a Retrospective Study from the EBMT Transplant Complications and Lymphoma Working Partys
No full text
Retrospective Comparison between 12-Gray and 8-Gray Total Body Irradiation (TBI) before Allogeneic Hematopoietic Cell Transplantation in Patients with Acute Lymphoblastic Leukemia in First Complete Remission
No full textAbstract
Introduction: Total body irradiation (TBI) continues to be an important part of the conditioning regimen for allogeneic hematopoietic cell transplantation (allo-HCT) in acute lymphoblastic leukemia (ALL). Previous dose escalation studies showed that higher than 12-Gray (Gy) was toxic and did not provide any apparent survival benefit - at least in patients (pts) transplanted in first complete remission (CR1) - thus establishing 12-Gy as the standard TBI dosage. Whether 8-Gy instead of 12-Gy TBI is sufficient in ALL CR1, as has been prospectively demonstrated for AML CR1 (Lancet Oncol 2012; 13: 1035-1044), has not yet been studied.
Methods : In this registry-based retrospective study of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (ALWP-EBMT), we compared outcomes of ALL-CR1 pts who underwent a matched-sibling donor (MSD) or matched-unrelated donor (MUD) allo-HCT (94% peripheral blood stem cells) with TBI-based conditioning at a total dose of 12-Gy vs 8-Gy. Patients included in this analysis had received fludarabine (Flu) as the sole chemotherapy counterpart of TBI (12-Gy vs 8-Gy TBIFlu).
Results: The median follow up for the whole cohort (n=639 pts) was 22.5 months (95% CI, 17.2-24.1) and did not differ between the 8-Gy (n=494) and 12-Gy (n= 145) TBIFlu treated pts. 25% pts had B-precursor ALL, 54% Philadelphia (Ph)-positive ALL and 21% T-ALL (p=0.008 between groups). Patients conditioned with 8-Gy TBIFlu were older than 12-Gy TBIFlu treated pts (median 55.7 vs 40.3 years, IQR 50.2-61.3 vs 27-50.2 years, <0.0001) and more frequently received in vivo T-cell depletion (71% vs 40%, <0.0001). All other characteristics were well balanced between 8-Gy vs 12-Gy groups including time from diagnosis to HCT (5.5 vs 5.8 months), Karnofksy <90% (34% vs 26%), minimal residual disease (MRD) positivity at HCT (37% vs 43%), MUD (72% vs 68%) and type of GvHD prevention. Engraftment failure was low and below 2% in both groups. Overall, 29% and 27% of 8-Gy vs 12-Gy treated patients died, with the main causes of death not differing between groups (relapse 41% vs 44%, infections 26% vs 24%, GVHD 12.6% vs 12.7%, respectively). Both in univariate and in the age-adjusted Cox proportional-hazards analysis, relapse (REL), non-relapse mortality (NRM), leukemia-free survival (LFS), overall survival (OS), and GVHD-free, relapse-free survival (GRFS) were not influenced by TBI dose (Figure 1, Table 1). These results were confirmed when we focused on pts aged <55 years (median age 47 years; 8-Gy 229 pts vs 12-Gy 131 pts). In the multivariate analysis, an incremental age of 10 years was associated with increased NRM risk (hazard ratio [HR] 1.66, 95% CI, 1.25-2.22) and reduced OS (HR 1.32, 1.09-1.59). Ph+ and T-ALL pts had significantly better survival outcomes than Ph- B-ALL pts, mainly due to significantly fewer relapses (Table 1).
Conclusion: Although there were limitations to this study (TBI dose and age were correlated; missing data on TBI fractionation; missing MRD data for nearly one-third of the pts) this retrospective analysis was able to investigate the effect of TBI total dose independently from the chemotherapy counterpart (TBIFlu regimen only) and suggests that 12-Gy and 8-Gy results in similar outcomes in ALL patients transplanted in CR1. Whether this is also true for more advanced disease (>=CR2) and/or young adults) cannot be answered, as our study included only CR1 pts, few of whom were below 25 years of age. The reduced REL risk of Ph+ B-ALL pts is probably due to the increased use of tyrosine kinase inhibitors (TKIs) pre- and post-transplant. Clinically, these results suggest 8-Gy TBI as sufficient for ALL patients transplanted in CR1 with no additional benefit of augmenting the conditioning intensity to 12-Gy, a finding which should be validated in prospective trials.
Figure 1 Figure 1.
Disclosures
Spyridonidis: Menarini: Current Employment. Labopin: Jazz Pharmaceuticals: Honoraria. Giebel: Janssen: Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau. Peric: Therakos: Honoraria; servier: Honoraria; MSD: Honoraria; Astellas: Honoraria; NOVARTIS: Honoraria; Abbvie: Honoraria; Pfizer: Honoraria. Schönland: Janssen: Honoraria, Other: Travel grants, Research Funding; Pfizer: Honoraria; Prothena: Honoraria, Other: Travel grants; Takeda: Honoraria, Other: Travel grants; Sanofi: Research Funding. Kröger: Novartis: Research Funding; Riemser: Honoraria, Research Funding; Sanofi: Honoraria; Neovii: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Gilead/Kite: Honoraria; Celgene: Honoraria, Research Funding; AOP Pharma: Honoraria. Stelljes: Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Kite/Gilead: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Medac: Speakers Bureau; Celgene/BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau. Schroeder: JAZZ: Honoraria, Research Funding. McDonald: BioCryst Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees. Ganser: Novartis: Honoraria; Jazz Pharmaceuticals: Honoraria; Celgene: Honoraria. Wulf: Novartis: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Clinigen: Consultancy, Honoraria. Bazarbachi: 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; Amgen: 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; Hikma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees
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
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
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