Long-term safety of siltuximab in patients with idiopathic multicentric Castleman disease: a prespecified, open-label, extension analysis of two trials.

BACKGROUND:Siltuximab is recommended by international consensus as a first-line treatment for idiopathic multicentric Castleman disease on the basis of durable efficacy and safety data. This study was done to assess the long-term safety and activity of siltuximab over up to 6 years of treatment. METHODS:This study is a prespecified open-label extension analysis of a phase 1 trial (NCT00412321) and a phase 2 trial (NCT01024036), done at 26 hospitals worldwide. Patients in both studies were at least 18 years old with histologically confirmed, symptomatic Castleman disease. This extension study enrolled 60 patients who completed the previous trials without disease progression on siltuximab. Patients received siltuximab infusions of 11 mg/kg every 3 weeks (which could be extended to 6 weeks) for up to 6 years. Descriptive statistics were used to summarise the data. No formal hypothesis testing was performed. The primary endpoint was the safety of siltuximab, assessed at each dosing cycle. The study was registered with ClinicalTrials.gov, number NCT01400503 and with EudraCT, number 2010-022837-27. FINDINGS:Patient enrolment into the phase 1 trial was from June 20, 2005, to Sept 15, 2009, and enrolment into the phase 2 trial was from Feb 9, 2010, to Feb 3, 2012. Patients were enrolled in this long-term extension from April 1, 2011, to Jan 15, 2014. Median follow-up was 6 years (IQR 5·11-7·76). Median treatment duration, from the beginning of the previous trials to the end of the present study, was 5·5 years (IQR 4·26-7·14). Siltuximab was well tolerated; however, adverse events of grade 3 or worse were reported in 36 (60%) of 60 patients with the most common being hypertension (eight [13%]), fatigue (five [8%]), nausea (four [7%]), neutropenia (four [7%]), and vomiting (three [5%]). 25 (42%) patients reported at least one serious adverse event, which most commonly was an infection (eight [13%]). Only two serious adverse events, polycythaemia and urinary retention, were considered related to siltuximab treatment. 18 patients discontinued before study completion, either to receive siltuximab locally (eight) or because of progressive disease (two), adverse events (two), or other reasons (six). No deaths were reported. INTERPRETATION:These results show that siltuximab is well tolerated long term and provides important evidence for the feasibility of the life-long use required by patients with idiopathic multicentric Castleman disease. FUNDING:Janssen R&D and EUSA Pharma

Simulador educativo de tecnología en informática y trabajo social (S.E.T.I.T.S).

Diseñar e implementar un simulador educativo que evalúe y fortalezca el conocimiento sobre las áreas de intervención social que tienen los graduados y estudiantes del Programa de Trabajo Social del centro regional Girardot del semestre I-2018.El proyecto es realizado principalmente con el fin de llevar de la mano y brindar un acompañamiento a los egresados del programa de Trabajo Social de la Corporación Universitaria Minuto de Dios Centro Regional Girardot, teniendo en cuenta los estudios y el análisis realizado a este tipo de población, el cual presenta falencias a la hora de enfrentase a la vida laboral en el tema de entrevistas, presentación personal, presentación de hoja de vida, el léxico que se debe manejar a la hora de expresarse en diferentes tipos de ambientes y entorno laboral, esto en cuanto a la parte de egresados. En cuanto a los alumnos que se encuentran en la etapa de prácticas profesionales, se enfoca en el acompañamiento por parte de los tutores resolviendo cualquier tipo de duda o información que requieran en el proceso, teniendo en cuenta que esta fase es muy importante para el profesional en formación y que este proceso contribuye significativamente a la construcción de conocimiento y experiencia en el ámbito laboral. De acuerdo a la problemática, se decidió resolver de manera práctica y dinámica combinando el campo de los tecnólogos en informática mediante la implementación de un simulador que permite anticiparse a los conceptos básicos, la experiencia y demás falencias anteriormente mencionadas, dando de esta manera solución a dicha problemática. Para concluir se realizó una prueba piloto de forma muestral analizando las evidencias estadísticas de los resultados positivos que deja este exitoso simulador brindando bienestar para todos los alumnos y egresados del programa de Trabajo Social de la universidad Minuto de Dios, evidenciando los conocimientos adquiridos en la academia como Tecnólogos en Informática y contribuyendo al mejoramiento de la calidad del servicio que brinda la Universidad Minuto de Dios frente al acompañamiento y compromiso que tiene con sus alumnos y egresados.The project is realized with the purpose of carrying out, and providing an accompaniment to the graduates of the Social Work program of the University Corporation Minuto de Dios Girardot Regional Center, taking into account the studies and the analysis made to this type of population, which present shortcomings in the face of working life in the subject of interviews, personal presentation, presentation of resume, the lexicon that must be handled when expressing in different types of environment, environment and environment work, this in terms of the part of graduates. As for the part of the students who are in the stage of professional practices, its focus on the accompaniment by the tutors solving any type of doubt or information that they require in the process, taking into account that this phase is very important for the professional in training and that this process contributes significantly to the construction of knowledge and experience in the labor field. According to the problem it was decided to solve in a practical and dynamic way combining the technology or the field of the technologists in computer science through the implementation of a simulator that allows to anticipate to the basic concepts, the experience and other shortcomings previously mentioned, giving of this way solution to this problem. To conclude, a pilot test was carried out in a sample form, analyzing the statistical evidence of the positive results of this successful simulator, providing well-being for all students and graduates of the Social Work program at Minuto de Dios University, evidencing the knowledge acquired in the academy as Computer Technologists and contributing to the improvement of the quality of the service offered by the Minuto de Dios University in the face of the accompaniment and commitment it has with its students and alumni

Infinite ergodic theory and Non-extensive entropies

We bring into account a series of result in the infinite ergodic theory that we believe that they are relevant to the theory of non-extensive entropie

Comparison of survival in patients with T cell lymphoma after autologous and allogeneic stem cell transplantation as a frontline strategy or in relapsed disease.

We studied the roles of autologous (A) and allogeneic (allo) stem cell transplantation (SCT) in the treatment of 134 patients with T cell lymphoma (TCL) at our center. For frontline SCT, 58 patients were studied. The 4-year overall survival (OS) rates for ASCT (n = 47; median age, 49 years) and alloSCT (n = 11; median age, 55 years) groups were 76% and 54%, respectively (P \u3e .05). The 4-year OS rates for first complete remission (CR1) patients were 84% and 83%, respectively. For SCT for relapsed disease, 76 patients were studied (41 with ASCT and 35 with alloSCT). The 4-year OS rates were 50% and 36% for ASCT and alloSCT patients with chemosensitive disease, respectively (P \u3e .05). Those who were in CR2 and CR3 had 4-year OS rates of 59% and 53%, respectively. Similar results were also observed in patients with refractory disease (29% and 35%, respectively). These data suggest that a pre-SCT CR is associated with improved outcomes in TCL patients after SCT. Considering the 84% 4-year OS rates in CR1 patients and the unpredictable responses in patients with relapsed disease, we favor the use of ASCT as consolidation therapy after CR1. AlloSCT did not result in a superior outcome compared with ASCT

A phase 2, open-label, multicenter study of the long-term safety of siltuximab (an anti-interleukin-6 monoclonal antibody) in patients with multicentric Castleman disease

BackgroundMulticentric Castleman disease (MCD) is a rare, systemic lymphoproliferative disorder driven by interleukin (IL)-6 overproduction. Siltuximab, an anti-IL-6 monoclonal antibody, has demonstrated durable tumor and symptomatic responses in a multinational, randomized, placebo-controlled study of MCD.MethodsThis preplanned safety analysis was conducted to evaluate the long-term safety of siltuximab treatment among 19 patients with MCD who had stable disease or better and were enrolled in a phase-1 study and subsequent ongoing, open-label, phase-2 extension study. Dosing was 11 mg/kg administered intravenously every 3 weeks, per protocol, or every 6 weeks at the investigator's discretion. Safety monitoring focused on potential risks associated with the anti-IL-6 mechanism of action. Investigator-assessed disease control status was also documented.ResultsMedian treatment duration for the 19 patients was 5.1 (range 3.4, 7.2) years, with 14 (74%) patients treated for >4 years. Grade-≥3 adverse events (AEs) reported in >1 patient included hypertension (n = 3) and nausea, cellulitis, and fatigue (n = 2 each). Grade-≥3 AEs at least possibly attributed to siltuximab were leukopenia, lymphopenia, and a serious AE of polycythemia (n = 1 each). Hypertriglyceridemia and hypercholesterolemia (total cholesterol) were reported in 8 and 9 patients, respectively. No disease relapses were observed, and 8 of 19 patients were able to switch to an every-6-week dosing schedule.ConclusionsAll MCD patients in this extension study have received siltuximab for a prolonged duration (up to 7 years) without evidence of cumulative toxicity or treatment discontinuations and with few serious infections. All patients are alive, demonstrate sustained disease control, and continue to receive siltuximab

Pre-treatment maximum standardized uptake value predicts outcome after frontline therapy in patients with advanced stage follicular lymphoma

The impact of pre-treatment maximum standardized uptake value (SUVmax) on the outcome of follicular lymphoma (FL) following specific frontline regimens has not been explored. We performed a retrospective analysis of 346 patients with advanced stage follicular lymphoma (FL) without histological evidence of transformation, and analyzed the impact of SUVmax on outcome after frontline therapy. Fifty-two (15%) patients had a SUVmax >18, and a large lymph node ≥6 cm was the only factor associating with SUVmax >18 on multivariate analysis (odds ratio 2.7, 95% confidence interval [CI]: 1.3-5.3, P=0.006). The complete response rate was significantly lower among patients treated with non-anthracycline-based regimens if SUVmax was >18 (45% vs. 92%, P18 was associated with significantly shorter progression-free survival among patients treated with non-anthracycline-based regimens (77 months vs. not reached, P=0.02), but not among patients treated with R-CHOP (P=0.73). SUVmax >18 associated with shorter overall survival (OS) both in patients treated with R-CHOP (8-year OS 70% vs. 90%, P=0.02) and non-anthracycline-based frontline regimens (8-year OS 50% vs. 85%, P=0.001). In conclusion, pre-treatment PET scan has prognostic and predictive value in patients with advanced stage FL receiving frontline treatment