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Steven A Feldman - One of the best experts on this subject based on the ideXlab platform.
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long duration complete Remissions of diffuse large b cell lymphoma after anti cd19 chimeric antigen receptor t cell therapy
Molecular Therapy, 2017Co-Authors: James N Kochenderfer, Robert Somerville, Tangying Lu, James Chihhsin Yang, Richard M Sherry, Steven A Feldman, Lori Mcintyre, John J Rossi, Steven A RosenbergAbstract:T cells expressing anti-CD19 chimeric antigen receptors (CARs) can induce complete Remissions (CRs) of diffuse large B cell lymphoma (DLBCL). The long-term durability of these Remissions is unknown. We administered anti-CD19 CAR T cells preceded by cyclophosphamide and fludarabine conditioning chemotherapy to patients with relapsed DLBCL. Five of the seven evaluable patients obtained CRs. Four of the five CRs had long-term durability with durations of Remission of 56, 51, 44, and 38 months; to date, none of these four cases of lymphomas have relapsed. Importantly, CRs continued after recovery of non-malignant polyclonal B cells in three of four patients with long-term complete Remissions. In these three patients, recovery of CD19 + polyclonal B cells took place 28, 38, and 28 months prior to the last follow-up, and each of these three patients remained in CR at the last follow-up. Non-malignant CD19 + B cell recovery with continuing CRs demonstrated that Remissions of DLBCL can continue after the disappearance of functionally effective anti-CD19 CAR T cell populations. Patients had a low incidence of severe infections despite long periods of B cell depletion and hypogammaglobulinemia. Only one hospitalization for an infection occurred among the four patients with long-term CRs. Anti-CD19 CAR T cells caused long-term Remissions of chemotherapy-refractory DLBCL without substantial chronic toxicities.
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allogeneic t cells that express an anti cd19 chimeric antigen receptor induce Remissions of b cell malignancies that progress after allogeneic hematopoietic stem cell transplantation without causing graft versus host disease
Journal of Clinical Oncology, 2016Co-Authors: Jennifer N Brudno, Robert Somerville, Jeremy J Rose, David Halverson, Daniel H Fowler, Juan Geabanacloche, Steven Z Pavletic, Dennis D Hickstein, Tangying L Lu, Steven A FeldmanAbstract:PurposeProgressive malignancy is the leading cause of death after allogeneic hematopoietic stem-cell transplantation (alloHSCT). After alloHSCT, B-cell malignancies often are treated with unmanipulated donor lymphocyte infusions (DLIs) from the transplant donor. DLIs frequently are not effective at eradicating malignancy and often cause graft-versus-host disease, a potentially lethal immune response against normal recipient tissues.MethodsWe conducted a clinical trial of allogeneic T cells genetically engineered to express a chimeric antigen receptor (CAR) targeting the B-cell antigen CD19. Patients with B-cell malignancies that had progressed after alloHSCT received a single infusion of CAR T cells. No chemotherapy or other therapies were administered. The T cells were obtained from each recipient’s alloHSCT donor.ResultsEight of 20 treated patients obtained Remission, which included six complete Remissions (CRs) and two partial Remissions. The response rate was highest for acute lymphoblastic leukemia, ...
Donald L Trump - One of the best experts on this subject based on the ideXlab platform.
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calcitriol 1 25 dihydroxycholecalciferol enhances mast cell tumour chemotherapy and receptor tyrosine kinase inhibitor activity in vitro and has single agent activity against spontaneously occurring canine mast cell tumours
Veterinary and Comparative Oncology, 2010Co-Authors: E K Malone, Duncan S. Russell, Kenneth M. Rassnick, David Ruslander, Candace S. Johnson, Joseph J. Wakshlag, Ramsey Alsarraf, Donald L TrumpAbstract:: Calcitriol potentiates the effect of multiple chemotherapy agents in a variety of tumour models. In this study, we examine whether calcitriol increases chemotherapy or tyrosine kinase inhibitor in vitro cytotoxicity in canine mastocytoma C2 cells. We also evaluate the in vivo effect of DN101, a highly concentrated oral formulation of calcitriol designed specifically for cancer therapy, as a single-agent therapy in dogs with mast cell tumours (MCTs). Calcitriol exhibits synergistic, antiproliferative activity when used in combination with CCNU, vinblastine, imatinib or toceranib in vitro. The concentrations required for 50% growth inhibition were generally two- to six-fold lower when the drugs were used in combination than when used individually. High-dose oral calcitriol induced Remission in 4 of 10 dogs (one complete Remission, three partial Remissions), although the majority experienced toxicity, necessitating discontinuation of the trial. Further evaluation of calcitriol in combination therapy for dogs with MCTs is warranted.
Michael E. J. Lean - One of the best experts on this subject based on the ideXlab platform.
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Type 2 diabetes Remission: 2 year within-trial and lifetime-horizon cost-effectiveness of the Diabetes Remission Clinical Trial (DiRECT)/Counterweight-Plus weight management programme
Diabetologia, 2020Co-Authors: Andrew Davies, Andrew Briggs, Louise Mccombie, C. Martina Messow, Eleanor Grieve, Wilma S. Leslie, Roy Taylor, Michael E. J. LeanAbstract:Aims/hypothesis Approximately 10% of total healthcare budgets worldwide are spent on treating diabetes and its complications, and budgets are increasing globally because of ageing populations and more expensive second-line medications. The aims of the study were to estimate the within-trial and lifetime cost-effectiveness of the weight management programme, which achieved 46% Remissions of type 2 diabetes at year 1 and 36% at year 2 in the Diabetes Remission Clinical Trial (DiRECT). Methods Within-trial analysis assessed costs of the Counterweight-Plus intervention in DiRECT (including training, programme materials, practitioner appointments and low-energy diet), along with glucose-lowering and antihypertensive medications, and all routine healthcare contacts. Lifetime cost per quality-adjusted life-year (QALY) was estimated according to projected durations of Remissions, assuming continued relapse rates as seen in year 2 of DiRECT and consequent life expectancy, quality of life and healthcare costs. Results Mean total 2 year healthcare costs for the intervention and control groups were £3036 and £2420, respectively: an incremental cost of £616 (95% CI –£45, £1269). Intervention costs (£1411; 95% CI £1308, £1511) were partially offset by lower other healthcare costs (£796; 95% CI £150, £1465), including reduced oral glucose-lowering medications by £231 (95% CI £148, £314). Net Remission at 2 years was 32.3% (95% CI 23.5%, 40.3%), and cost per Remission achieved was £1907 (lower 95% CI: intervention dominates; upper 95% CI: £4212). Over a lifetime horizon, the intervention was modelled to achieve a mean 0.06 (95% CI 0.04, 0.09) QALY gain for the DiRECT population and mean total lifetime cost savings per participant of £1337 (95% CI £674, £2081), with the intervention becoming cost-saving within 6 years. Conclusions/interpretation Incorporating the lifetime healthcare cost savings due to periods of Remission from diabetes and its complications, the DiRECT intervention is predicted to be both more effective (QALY gain) and cost-saving in adults with type 2 diabetes compared with standard care. This conclusion appears robust to various less favourable model scenarios, providing strong evidence that resources could be shifted cost-effectively to support achieving Remissions with the DiRECT intervention. Trial registration ISRCTN03267836 Graphical abstract
Jerzy Piecuch - One of the best experts on this subject based on the ideXlab platform.
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Type 2 Diabetes Remission 5 Years After Laparoscopic Sleeve Gastrectomy: Multicenter Cohort Study
Obesity Surgery, 2020Co-Authors: Magdalena Mizera, Michał Wysocki, Katarzyna Bartosiak, Paula Franczak, Hady Razak Hady, Piotr Kalinowski, Piotr Myśliwiec, Michał Orłowski, Rafał Paluszkiewicz, Jerzy PiecuchAbstract:Purpose Bariatric surgery is no longer considered only as a weight loss surgery but also a way of treating obesity-related comorbidities such as type 2 diabetes mellitus (T2DM). Short-term T2DM Remissions in patients undergoing laparoscopic sleeve gastrectomy (LSG) have been shown, but there are very few reports on the mid-term results. We aimed to assess the Remission rate of T2DM in obese patients after LSG throughout 5-year follow-up. Materials and Methodology We performed a retrospective multicenter cohort analysis of 240 patients who underwent LSG. We assessed the Remission rate of T2DM 1 year and 5 years after surgery. Results Forty-six percent of patients achieved T2DM Remission 5 years after LSG. The Remission group had better weight loss results (median% of total weight loss 5 years after: 30.1% (22.9–37.0) vs 23.0% (13.7–30.2), p
P. Ritz - One of the best experts on this subject based on the ideXlab platform.
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Diabetes Remission and Relapse After Bariatric Surgery: a Nationwide Population-Based Study
Obesity Surgery, 2020Co-Authors: C. Conte, M. Lapeyre-mestre, H. Hanaire, P. RitzAbstract:Purpose The long-term impact of bariatric surgery on the Remission of type 2 diabetes (T2DM) remains to be clarified through large nationally representative cohorts. The objectives were to determine the incidence of T2DM Remission and relapse after bariatric surgery, to determine the factors associated with Remission and to establish a profile for patients at risk for relapse. Materials and Methods We conducted a population-based cohort study using data from the French national health insurance database (Systeme national des données de santé [SNDS]). We had access to exhaustive regional data between 2013 and 2017 and to a national representative sample of the French population (EGB) from 2008 to 2018. Patients were included if they were adults and diabetics with incidental bariatric surgery. Results This study shows that 50% of patients are in Remission from diabetes after bariatric surgery within a median of 2 to 4 months. Diabetes relapse was observed in 13–20% within 10 years. The factors favouring Remission already described were noted (non-insulin-dependent diabetes) and original factors were also identified, in particular the advantage of bypass surgery over sleeve gastrectomy, with more Remissions and fewer relapses. Conclusion This study highlights a 50% prevalence of Remission and a low prevalence of relapse. There are non-modifiable risk factors for Remission and relapse (characteristics of diabetes, age, lipid-lowering therapy) and modifiable factors (type of surgery). Identifying these factors is essential for optimal management of patients. Additional data are essential to confirm the results of our analysis of the factors associated with relapse.
