Active clinical trials for "Graft vs Host Disease"

Despite significant progress in overall survival and event-free survival in Pediatric Hematopoietic Stem Cell Transplant (HSCT), therapeutic options for graft-versus-host disease control remain limited, particularly in steroid-refractory patients. Several strategies have been proposed in the last 20 years but so far, the results have been inconclusive, complicated by the small population afflicted, inconsistent treatment schedules, different disease classifications and diagnosis methods. The number of studies concerning pediatric patients are even smaller. First line therapy for acute graft-versus-host disease (aGVHD) is steroid treatment that achieve partial or complete remission of the disease in a variable percentage of cases (40-60%), depending mainly to severity of GVHD and number of organ involvement, with hepatic and gastrointestinal GVHD particularly refractory to steroid treatment. For second line therapy there is no a standardized strategy with a great variety of immunosuppressive treatment without a real superiority of a drug in comparison to another. Steroid refractory acute GVHD is therefore one of the most important challenges in HSCT field. One of the more promising routes, based on published data and clinical experience, is the off-label use of Infliximab, an anti-Tumor Necrosis Factor α drug (already approved for many rheumatologic and autoimmune diseases) administered as a second line treatment in patients with steroid-refractory aGVHD at the standardized dosage of 10 mg/kg, although limited evidence has been published to validate this subscription. Biological pattern that could explain susceptibly of GVHD to infliximab treatment could lie in physiopathology of acute gastrointestinal GVHD that may resemble ulcerative rectocolitis. In this case, relation to Therapeutic Drug Monitoring (TDM) and Tumor Necrosis Factor α (TNFα) levels could be critical in monitoring the efficacy of the drug and need of further doses. Limited published data and clinical experience show that Infliximab may be able to further control symptoms and inflammatory response in a promising percentage of treated patients, although some have no benefit from the treatment. The aim of this study is to analyze the role of TNFα concentration in aGVHD, its levels fluctuation and clinical response of GVHD to Infliximab treatment in steroid-refractory pediatric patients.

The granulocyte colony-stimulating factor (G-CSF)+antithymocyte globulin (ATG)-based protocols and posttransplantation cyclophosphamide (PTCy) protocols have been widely used for graft-versus-host disease (GVHD) prophylaxis in haploidentical related donor transplantation (haplo-HSCT). Nevertheless, severe acute GVHD remains an obstacle for haplo-HSCT. This study is aim to evaluate the efficacy of a modified protocol that includes PTCY and ATG in recipients of haplo-HSCT.

HLA-mismatched unrelated donor (MMUD) and HLA-haploidentical donor (Haplo Donor) hematopoietic stem cell transplantation (HSCT) is associated with increased graft-versus-host-disease (GVHD) and impaired survival. The chemokine receptor 5 (CCR5) antagonist maraviroc has immunomodulatory properties potentially beneficial for GVHD control as it can blockade lymphocyte chemotaxis without impairing T-cell function. The aim of this study is to evaluate the safety and efficacy of maraviroc combined with standard graft-versus-host-disease prophylaxis in patients with hematologic malignancies after allogeneic stem cell transplantation from HLA-Unrelated or HLA-Mismatched Related donors. Based on the results of our previously small sample study with maraviroc combined with cyclosporine/tacrolimus and methotrexate for prophylaxis of GVHD, the investigators plan to perform the clinical trail.

There is a significant (50-80%) risk of acute graft-versus-host disease(GVHD) and early mortality (30%) associated with high risk stem cell transplantation (SCT) such as that from a matched unrelated donor or HLA-mismatch sibling. Mycophenolate mofetil (MMF) has been shown to be an effective and safe immunosuppressant in the prevention and treatment of rejection after solid organ transplantation. Its role in acute GVHD prophylaxis in high risk SCT will be investigated in this clinical trial.

Chronic Graft-versus-Host Disease (cGVHD) is an important cause of morbidity and mortality in patients undergoing allogeneic bone marrow transplantation. cGVHD usually occurs after 100 days following transplantation and develops in 20-60% of transplant recipients. The incidence of cGVHD varies depending on the age of the marrow recipient, the use of sibling or unrelated donor bone marrow, the use of unmanipulated T cell-depleted bone marrow, and perhaps other factors. Clinically, cGVHD is characterized by multi-system disease, which frequently mimics the clinical features of autoimmune diseases. The manifestations include skin changes (lichenoid and sclerodermatous changes, changes in pigmentation, loss of accessory structures such as hair, dystrophic nails, and rash), joint contractures, severe cramping, hepatic dysfunctions, sicca syndrome, obstructive lung disease, esophageal dysmotility, weight loss, polyserositis, immunodeficiency, and autoantibodies including anti-nuclear antibody, anti-erythrocyte antibodies, and anti-platelet antibodies.

The investigators' hypothesis is that the graft-versus-tumor effect can be enhanced while minimizing the complications of graft-versus-host disease.

Oral mucositis (OM) is an inflammatory mucosal demolition frequently observed during treatments for neoplastic diseases such as chemotherapy or radiation therapy. The side effects of these treat-ments often drastically reduce patients' quality of life. OM are the result of the systemic consequences of chemotherapy and radiotherapy which, due to their cytotoxic and local effects, lead to pain and severe ulceration with a consequent decrease in the quality of life of affected subjects. Plasma Rich in Fibrin is often used to enhance soft tissue wound healing and fight bacterial sepsis through the presence of leukocytes within it. Aim of the retrospective study was to evaluate efficacy and safety of topic use of platelet gel in clinical management of oral mucositis in order to improve life quality of patients.

Allogeneic stem cell transplantation was developed to cure many patients with hematological malignancies. It results in the development of graft versus host disease (GVHD) in 30-70% of cases. Chronic GVHD diagnosis currently uses biopsies of affected organs (skin, liver, gastrointestinal tract) and / or the observation of typical clinical signs sufficient for diagnosis. However, the anatomical sites for biopsy including the digestive tract are not clearly identified (high or low biopsy) and may present risks in their realization in particular in patients weakened by blood disease or immunosuppression. PET-CT with 18F-FDG has already been evaluated in chronic inflammatory diseases such as Crohns disease with good sensitivity and specificity. It interest in the graft against the host was studied in acute forms of digestive and allows lesion mapping and monitoring the effectiveness of treatment. Among patients with chronic GVHD scleroderma form, PET with 18F-FDG enabled to view musculoskeletal uptakes localized to the affected areas identified with MRI. The investigators propose a study evaluating the sensitivity and specificity of the examination by PET-CT with 18F-FDG in the diagnosis of chronic GVHD compared to conventional diagnostic tools.

• The primary aim of the present trial is to assess in a randomized fashion the benefit on standard graft-versus-host disease (GVHD) prophylaxis of the addition of ATG-Fresenius S ® in transplants from matched related donors (MRD) and of anti-CD20 rituximab in transplants from matched unrelated donors (MUD). Both safety and efficacy of the treatment will be assessed, in particular in respect to the clinical status of the patient, i.e. prevention of graft failure and chronic GvHD and of Ebstein Barr virus (EBV) viremia for MUD patients. The conditioning proposed combines myeloablative drugs with a favorable safety profile such as treosulfan, thiotepa (Tepadina®) and fludarabine with the intent to reduce the traditional immediate and late toxicity of busulfan and cyclophosphamide.

The purpose of this study is to examine the gut bacteria, levels of peripheral blood inflammation markers, and symptoms in patients with and without chronic graft-versus-host disease (cGVHD) following allogeneic hematopoietic stem cell transplant (allo-HSCT). The hypothesis is that individuals with cGVHD will have lower levels of microbial diversity, higher levels of inflammatory metabolites in stool and peripheral measures, and higher levels of symptoms than individuals without cGVHD.