Active clinical trials for "Graft vs Host Disease"

The objective is to measure the frequency, functionality and phenotype of bone marrow-derived mesenchymal stromal cells in patients after allogeneic hematopoietic stem cell transplantation. Furthermore, the immune cell infiltrate of the bone marrow will be monitored at the same time. These results will be correlated with the extent of cytopenia and clinical graft-versus-host disease grading.

Validation of already described biomarkers on acute GVHD prediction and severity Fecal calprotectin and alpha 1 anti-trypsin, plasmatic RER3a, IL-8, Elafin, TNFaR1, IL-2R alpha, HGF

Intestinal acute graft-vs-host disease (GVHD) is a life-threatening complication after allogeneic hematopoietic cell transplantation. Non-invasive diagnostic procedures are still lacking and diagnosis is difficult. We hypothesized that contrast-enhanced ultrasound sonography (CEUS) could detect microcirculation changes of the bowel walls during intestinal GVHD and help to detect and monitor treatment response. We employed CEUS to prospectively evaluate intestinal GVHD in 83 consecutive transplant patients between 2008 and 2011. Fourteen /83 patients with biopsy-proven intestinal GVHD were selected as study group. Fourteen patients with biopsy-proven stomach GVHD without intestinal symptoms (N=16), normal volunteers (N=6) and patients with neutropenic enterocolitis (N=4), were chosen as control group. All patients were evaluated with both standard transabdominal ultrasonography (US) and CEUS at the onset of intestinal symptoms, during clinical follow up and at flare of symptoms. Standard US revealed non-specific bowel wall thickening, and simultaneous involvement of multiple intestinal segments in 9/14 patients. CEUS showed three distinct patterns of microcirculation changes that correlated with GVHD activity. These findings were not observed in the control group. Moreover, CEUS findings correlated with treatment response and predicted flare of intestinal symptoms. CEUS is a non-invasive, easily reproducible bed-side tool to detect and monitor intestinal GVHD.

This study aims to show that the MedGem indirect calorimetry measurement device will be feasible to use in children with GVHD. Also, it aims to show that children with chronic GVHD will have elevated REE that is not adequately predicted by standard equations.

The purpose of this study is to see the correlation of polarization and the expresison of chemokine receptors of T help cells after allogeneic hematopoietic stem cell transplantation and clinical course graft-versus-host disease.

Graft-versus-Host Disease (GVHD), is the most frequent and severe complication of allogeneic hematopoietic stem cell transplantation (HSCT). Much of our knowledge on the pathophysiology of GVHD has been gained from experimental models but far less from the study of the disease in humans. Recent developments in basic biology open new avenues to the development of biomarker sets that could predict GVHD severity and prognosis that could be tested and validated through well-designed multicenter clinical trials. The main goal of this project is to further our understanding of the pathogenic mechanisms of human GVHD on one hand, and of functional immune tolerance on the other. Furthermore, this study aims at setting up a clinically relevant biomarker set in human GVHD and immune tolerance in a discovery cohort. The objectives of this project are: 1. To define phenotypic, functional and molecular correlates of acute GVHD early after HSCT/at its onset 2. To study thymic reconstitution and the T-cell repertoire after HSCT during period 2 3. To identify functional and molecular correlates of immune tolerance in long-term survivors of HSCT 4. Preparing for biomarker validation into a clinical trial We propose a prospective analysis of a cohort of 680 patients transplanted from an HLA-identical sibling donor at Saint Louis hospital. Analyses will be performed during 3 critical, clinically relevant, periods. Period 1: Analysis at the onset of GVHD, or at the time of engraftment 30 days after HSCT in patients not developing GVHD. An additional blood sample will also be analyzed 90 days after HSCT. Period 2: Thymic function analysis using measurements of T-cell receptor excision circles (TREC) will be performed at 6 and 12 months post-transplant for all patients. T-cell receptor analysis on sorted T-cell populations will be performed by NGS. Period 3: In "tolerant" patients (patients more than 2 years after HSCT not requiring immunosuppressive treatment), or in patients still requiring immunosuppressive therapy after 2 years. We will also analyze the corresponding immune parameters for each donor. The longitudinal design of this study will allow us to provide an integrated view of GVHD pathophysiology and mechanisms of immune tolerance in human. Prospectively identified phenotypic, molecular or functional biomarkers will then be tested, in a subsequent study, from biological materials prospectively collected within the French wide CryoStem cohort. Thus, as the final task of this project, we will perform statistical analyses taking into account confounding clinical variables influencing the outcome (i.e. GVHD-related death or tolerance). Preparing for a clinical trial will need moving from classical Bioinformatics analyses into clinically relevant statistical analyses that include sequential biological measurement in the discovery set cohort. Main points that will be taken into accounts for this task are the followings; Transplant-related mortality (TRM) can be estimated in the range of 20%; 2year post-allogeneic HSCT TRM is mostly (even if totally) due to GVHD and its associated immune deficiency GVHD cumulative incidence can be estimated in the range of 40% 80 patients will be prospectively studied and 30 patients will be analyzed (cross sectional study) for part 3 only. Since GVHD-related mortality and tolerance are mutually exclusive situation the optimal calculation for the validation cohort can be expected This calculation will be the basis for the proposal of an interventional clinical trial.

This is a prospective single arm study with the study period from June 1st, 2019 to May 31st, 2020. An historical control group will be used in the study, which includes all patients received HSCT but not GI panel detection between June 1st, 2018 to May 31st, 2019. All patients receiving HSCT within the year at SCMC will be enrolled in the study. The stool samples will be collected from each patient at 2-3 time points, including the day before pre-conditioning (T1), 28+-3 days after HSCT (T2), and the day severe diarrhea present (T3). All the stool samples will be detected by the FilmArray GI panel, and the results as well as other clinical information including the laboratory examinations will be recorded and analyzed.

Acute Graft-versus-host disease(aGVDH) after allogeneic hematopoietic stem cell transplantation is one of the meaningful issues in aspect of patient's recovery and survival. in recent years, the understanding of the pathology of GVHD is much important to prevent or treat aGVHD. additionally, (oral) mucositis is one of the problems in patients with high dose chemotherapy, and mucositis by high-dose chemotherapy is related to HMGB-1 as proinflamtory cytokines. HMGB1 is a nuclear protein acts as a transcription factor, but, if it was released to the outside of cells by damaged cell or necrotic tissues, it works as cytokines for promoter of inflammation and cancers. at this point, there are no reported articles about correlation of HMGB1 and aGVHD in human. recently, we have seen excessive secretion of serum HMGB1 in mouse model, then base on this results, we will check correlation of HMGB1 and aGVHD/ oral mucositis in human.

The purpose of this study is to evaluate the presence and manifestations of ocular graft versus host disease in adults that had hematopoietic stem cell transplantation in the past 3 years at the sheba medical center, Israel. As well as correlate the degree of the presentation to the therapeutic protocol (chemotherapy and irradiation).

This study has the aim to analyze intestinal expression of cellular stress molecules in patients with intestinal GVHD. Patients with colitis and patients without intestinal inflammation will serve as controls.