View clinical trials related to Allogeneic Disease.
Filter by:Currently, transplantation centers across North America generally do not offer longitudinal rehabilitation programs and research is urgently needed to test the acceptability and effectiveness of these programs using innovative delivery strategies that have the potential for future scalability and to understand the associated costs. Through a strong collaboration between the PM Cancer Rehabilitation and Survivorship (CRS) and alloBMT teams, the principal investigators developed an innovative multicomponent rehabilitation intervention for patients undergoing alloBMT (CaRE-4-alloBMT). CaRE-4-alloBMT uses a person- centred strategy and a multidimensional approach targeting physical activity, nutrition, psychosocial distress and promoting self-management skills. Innovative components of CaRE-4-alloBMT include:1) Individualized progressive exercise prescriptions developed and monitored by CRS registered kinesiologists and supported with a web/mobile application (Physitrack) that allows customizable exercise prescriptions, tracking of exercise completion, and video tutorials; 2) Individualized nutrition plans and stepped stratified care (education, counselling, intervention) based on nutritional status and delivered by registered dietitians (alloBMT and CRS). 3) On-line e-modules (developed in collaboration with PM Oncology Education) provide interactive education to promote self-management skills on crucial topics; 4) Remote monitoring using FitbitTM devices to monitor patients physical activity, caloric intake, and sleep for duration of the program; 5) Remote clinical support: Pre/Post discharge, patients will have scheduled (PHS) remote check-ins and health coaching sessions with a member of the CRS team (phone or MS Teams video). Objectives: i) To test the feasibility and safety of CaRE-4-alloBMT plus standard best practice cancer care compared to standard best practice cancer care alone; ii) To assess the preliminary efficacy of CaRE-4-alloBMT on physical function, disability, nutritional status, distress, QoL, healthcare utilization, and survival and estimate program return on investment.
Scientific context Epstein-Barr virus has a causal role in the pathogenesis of multiple distinct lymphomas. Post-transplant lymphoproliferative diseases (PTLD) are the most frequent EBV-induced proliferations. PTLD after allogeneic stem cell transplantation has an incidence lower than 5% but may increase up to 10-20% in patients with established risk factors. EBV-DNAemia is predictive of EBV-PTLD and is routinely performed using qPCR on whole blood. Preemptive therapeutic strategies with anti-CD20 antibody are used when patients are above a defined EBV-DNAemia threshold. This approach remains limited since it does not discriminate between an EBV-induced lymphoproliferation (latent cycle) and/or a replicating virus (replicative cycle). Epigenetic modifications plays a central role in regulating the switch from latent to lytic gene expression. Specific DNA modifications can be regarded as molecular signatures for EBV genomes associated with the status of the viral infection (latent vs lytic). Accordingly, these signatures may be envisioned as a potent tool to characterize the state of the viral infection in vivo. Description of the project Our primary objective is to estimate the respective percentages of EBV-lytic and EBV-latent genomes (proliferating cells) in patients presenting with a high EBV-DNAemia after allogeneic stem cell transplantation HSCT by analysing the epigenetic modifications of EBV genome on specific sites. Our secondary objectives are i) to determine risk factors associated with each "latent versus lytic EBV" profiles and ii) to correlate the "latent versus lytic EBV" profiles with response to rituximab infusion and patient outcomes. For this purpose, a retrospective study (n=80) and a prospective study (estimation n=58) will be established. The different steps of this project are: 1. To study epigenetic modifications. The laboratory is developing a new approach to distinguish between latent and lytic genomes. 2. To realize quantitative analysis by RT-PCR of different EBV transcripts specific of the latent or of the lytic phase of the virus This method will be applied on RNA extracted from patient blood samples with elevated EBV viral load, under condition preserving RNA integrity. The results will be validated on a prospective cohort of HSCT patients (n=58) (Saint-Antoine Hospital and La Pitié-Salpêtrière Hospital). 3. To perform quantitative analysis of EBV genomes in plasma, saliva and total blood samples by current routine procedures In addition to total blood samples, plasma and saliva will be collected since free viral particles are known to accumulate in these biological fluids upon EBV reactivation. These samples will be treated by normalized procedures that are routinely used in the medical virology laboratory to quantify EBV in human samples. Expected results By establishing a simple method for studying epigenetic modifications of EBV genomes, we expect to understand the significance of high EBV viral load and the pathophysiology of post-HSCT PTLD. We aim to distinguish between the latent / lytic profiles of HSCT patients and to correlate their respective risks for developing PTLD. Establishing the epigenetic EBV profile in the post-HSCT setting when facing increase viral load and PTLD will improve our understanding of the biological mechanisms determining EBV-status in post-HSCT. This should improve major medical and economical issues. These results could have a major therapeutic