Data Collection Study of Patients With Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT With RIC
Ontology highlight
ABSTRACT:
DISEASE(S): Primary Immunodeficiency Diseases,Crohn’s Disease,Inflammatory Conditions,Inherited Metabolic Disorders (imd),Rheumatoid Arthritis,Bone Marrow Failure Disorders,Pancytopenia,Congenital Bone Marrow Failure Syndromes,Metabolic Diseases,Hereditary Anemias,Primary Immunodeficiency (pid)
PROVIDER: 2349983 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:<p>Allogeneic hematopoietic cell transplantation (HCT) is the only known curative option for many hematologic disorders. After transplantation, many patients develop immune mediated disorders that may be life-threatening. Post-HCT immune mediated disorders are rare relative to other diseases but the prototype of graft versus host disease (GVHD) develops in 30-70% of patients. The morbidity and mortality associated with these HCT-associated immune mediated disorders are major barriers to successful use of transplantation to cure rare hematologic malignancies such as leukemia, lymphoma, multiple myeloma, myelodysplastic/myeloproliferative syndromes amongst other diseases.</p> <p>The purpose of this study is to characterize and more completely define the onset and course of immune mediated disorders after allogeneic HCT, focusing on participants who develop cutaneous sclerosis, bronchiolitis obliterans syndrome (BOS), late acute graft-vs.-host disease (GVHD), and chronic GVHD. <ul> <li>Of the participants undergoing allogeneic hematopoietic cell transplantation (HCT), can we, the researchers better identify who will develop immune-mediated disorders, what types of disorders participants will have, and whether these disorders will be severe or respond to currently available therapies?</li> </ul> </p> <p>This is a longitudinal study of 1118 individuals (1081 adults and 100 children). Those participating in this study will be evaluated over a 3 year period at 9 study sites. Participants will be enrolled pre-transplant, or up to day 121 post transplantation. This wide enrollment window will allow sites to use recruitment methods that are most efficient at their institutions. At least 2 years of follow-up will ensure an adequate sample size, and sufficient time for observation of the full spectrum of immune mediated disorders. The data of 1023 individuals have been submitted to dbGaP.</p>
| phs001331 | dbGaP
Project description:CD4+Foxp3+ regulatory T cells (Treg) are a subpopulation of T cells, which regulate the immune system and enhance immune tolerance after transplantation. Donor-derived Treg prevent the development of lethal acute graft and host disease (GVHD) in murine models of allogeneic hematopoietic cell transplantation. It was reported that a single treatment of the agonistic antibody to Death receptor 3 (DR3) in donor mice resulted in the expansion of donor derived Treg and prevented acute GVHD, although the precise role of DR3 signaling in GVHD has not been elucidated. We analyzed the gene expression profile, immune phenotype, and function of DR3-activated Treg in a murine model of allogeneic hematopoietic cell transplantation. CD4+Foxp3+ Treg were sorted from the mice stimulated with anti-DR3 or control antibody using fluorescence-activated cell sorter for RNA extraction and hybridization on Affymetrix microarrays.
2016-06-28 | E-GEOD-83743 | biostudies-arrayexpress
Project description:The aim of this study is to assess the Fecal Microbiota Transplantation (FMT) efficacy in the prevention of allogeneic hematopoietic stem cell transplantation (allo-HSCT) complications and particularly Graft versus Host Disease (GvHD).
The hypothesis of this study is that allogeneic FMT may improve outcomes of these patients.
| 2381286 | ecrin-mdr-crc
Project description:CD4+Foxp3+ regulatory T cells (Treg) are a subpopulation of T cells, which regulate the immune system and enhance immune tolerance after transplantation. Donor-derived Treg prevent the development of lethal acute graft and host disease (GVHD) in murine models of allogeneic hematopoietic cell transplantation. It was reported that a single treatment of the agonistic antibody to Death receptor 3 (DR3) in donor mice resulted in the expansion of donor derived Treg and prevented acute GVHD, although the precise role of DR3 signaling in GVHD has not been elucidated. We analyzed the gene expression profile, immune phenotype, and function of DR3-activated Treg in a murine model of allogeneic hematopoietic cell transplantation.
2016-06-28 | GSE83743 | GEO
Project description:A protein signature that could identify graft-versus-tumor (GVT) activity without graft-versus-host disease (GVHD), would allow for customized treatment plans following hematopoietic cell transplantation (HCT). Using orthogonal three-dimensional intact-protein analysis system (IPAS)
coupled with protein tagging and novel systems biology pipeline, we identified a signature of 49 proteins that are significantly increased in the plasma of HCT patients who received donor lymphocyte injection for tumor relapse and develop GVT without GVHD.
2017-05-03 | MSV000081057 | MassIVE
Project description:Inducing graft acceptance without chronic immunosuppression remains an elusive goal in organ transplantation. Recent data demonstrate that non-self recognition by graft infiltrating macrophages initiates transplant rejection. Using an experimental transplantation mouse model, we isolated graft-infiltrating macrophages from two transplantation settings: untreated rejecting mice and treated with mTORi-HDL nanobiologics. We used microarrays to detail the global programme of gene expression underlying macrophage dependent organ transplant rejection and identified distinct classes of up-regulated genes during this process, which are down-regulated following tolerogenic treatment with mTORi-HDL nanobiologics.
2018-10-31 | GSE119370 | GEO
Project description:To assess if gene expression signatures could predict acute graft-versus-host disease, we examined the global gene expression profiles of peripheral blood mononuclear cells at day +14 post-transplantation from 94 patients undergoing allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning.
2010-06-09 | E-MEXP-1824 | biostudies-arrayexpress
Project description:αβT cell- and B cell-depleted HLA-haploidentical haematopoietic stem cell transplantation is a life-saving therapeutic option to treat patients with high-risk leukemia. The G-CSF treatment stimulates mobilization from the bone marrow to blood of hematopoietic stem cells (HSC), and this manipulated graft also contains mature donor-derived NK and γδT cells, both exerting graft-versus-leukemia activity and control of infections at early stages after transplantation. The G-CSF-induced mobilization in the donor causes relevant increases of different myeloid cells, including polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC). PMN-MDSC are present in high proportions in the graft and exert a sharp inhibition on the effector functions of co-infused mature NK cells. Conversely, low frequencies of PMN-MDSCs are detected in the blood of non-mobilized healthy donors. We used microarray technology to identify possible differences in the transcriptional programme of PMN-MDSCs isolated from blood of G-CSF mobilized donors as compared to those of non-mobilized healthy individuals.
2021-05-19 | GSE159069 | GEO
Project description:The objective of this study is to evaluate the efficacy of using a reduced-intensity condition (RIC) regimen with umbilical cord blood transplant (UCBT), double cord UCBT, matched unrelated donor (MUD) bone marrow transplant (BMT) or peripheral blood stem cell transplant (PBSCT) in patients with non-malignant disorders that are amenable to treatment with hematopoietic stem cell transplant (HSCT). After transplant, subjects will be followed for late effects and for ongoing graft success.
| 2153130 | ecrin-mdr-crc
Project description:<p><strong>BACKGROUND:</strong> Hematopoietic stem cell transplantation is a curative procedure for a variety of conditions. Despite major advances, a plethora of adverse clinical outcomes can develop post-transplantation including graft-versus-host disease and infections, which remain the major causes of morbidity and mortality. There is increasing evidence that the gastrointestinal microbiota is associated with clinical outcomes post-hematopoietic stem cell transplantation. Herein, we investigated the longitudinal dynamics of the gut microbiota and metabolome and potential associations to clinical outcomes in pediatric hematopoietic stem cell transplantation at a single centre.</p><p><strong>RESULTS:</strong> On admission (baseline), the majority of patients presented with a different gut microbial composition in comparison to healthy control children with a significantly lower alpha diversity. A further, marked decrease in alpha diversity was observed immediately post-transplantation and in most microbial diversity, and composition did not return to baseline status while hospitalized. Longitudinal trajectories identified continuous fluctuations in microbial composition, with the dominance of a single taxon in a significant proportion of patients. Using pam clustering, three clusters were observed in the dataset. Cluster 1 was common pre-transplantation, characterized by a higher abundance of <em>Clostridium XIVa</em>, <em>Bacteroides</em> and <em>Lachnospiraceae</em>; cluster 2 and cluster 3 were more common post-transplantation with higher abundance of <em>Streptococcus</em> and <em>Staphylococcus</em> in the former whilst <em>Enterococcus</em>, <em>Enterobacteriaceae</em> and <em>Escherichia</em> predominated in the latter. Cluster 3 was also associated with a higher risk of viraemia. Likewise, further multivariate analysis reveals <em>Enterobacteriaceae</em>, viraemia, use of total parenteral nutrition and various antimicrobials contributing towards cluster 3, <em>Streptococcaceae</em>, <em>Staphylococcaceae</em>, <em>Neisseriaceae</em>, vancomycin and metronidazole contributing towards cluster 2. <em>Lachnospiraceae</em>, <em>Ruminococcaceae</em>, <em>Bifidobacteriaceae</em> and not being on total parenteral nutrition contributed to cluster 1. Untargeted metabolomic analyses revealed changes that paralleled fluctuations in microbiota composition; importantly, low fecal butyrate was associated with higher risk of viraemia.</p><p><strong>CONCLUSIONS:</strong> These findings highlight the frequent shifts and dominations in the gut microbiota of pediatric patients undergoing hematopoietic stem cell transplantation. The study reveals associations between the fecal microbiota, metabolome and viraemia. To identify and explore the potential of microbial biomarkers that may predict risk of complications post-HSCT, larger multi-centre studies investigating longitudinal microbial profiling in pediatric hematopoietic stem cell transplantation are warranted.</p>
2022-05-11 | MTBLS4065 | MetaboLights