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.

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.

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.

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.

Prospective, observational, multicentre, spontaneous, non-interventional study This study will evaluate all consecutive patients who develop chronic graft-versus-host disease, reported by the Italian GITMO centers according to a standardized Web platform for real-time, onsite data collection. The platform for data collection will be based on a software prototype developed by the Clinica di Ematologia di Ancona Transplant Center for the management of patients with chronic graft-versus-host disease. This software has been integrated with algorithms that automatically determine: severity of chronic graft-versus-host disease and overall response according to the 2015 NIH consensus criteria.

Cannabidiol (CBD), a non-psychotropic ingredient of Cannabis sativa possesses potent anti-inflammatory and immunosuppressive properties. In a recent prospective phase II study (NCT01385124) 48 consecutive adult patients undergoing allogeneic hematopoietic cell transplantation were given CBD 300 mg/day starting 7 days before transplantation until day 30, on top of standard GVHD prophylaxis consisting of cyclosporine and a short course of methotrexate. There were no grade 3-4 toxicities attributed to CBD. None of the patients developed acute GVHD while consuming CBD. With a median follow-up of 16 months, the cumulative incidence rates of grade 2-4 and grade 3-4 acute GVHD by day 100 were 12.1% and 5%, respectively. Compared to 101 historical control subjects given standard GVHD prophylaxis, the hazard ratio of developing grade 2-4 acute GVHD among subjects treated with CBD plus standard GVHD prophylaxis was 0.3 (p=0.0002). Among patients surviving more than 100 days, the cumulative incidence of moderate-to-severe chronic GVHD at 12 and 18 months were 20% and 33%, respectively. The aim of this study is to explore the safety and efficacy of extended use of CBD until day 100 in the prevention of acute and chronic GVHD.

Patients with acute leukemia relapsing after allotransplant and who respond to anti-leukaemia interventions are at high-risk of a second relapse. Previous studies from investigators reported an association between a positive minimal residual disease (MRD)-test after transplant and an increased risk of subsequent relapse. Also, patients developing chronic graft-versus-host disease (GvHD) after receiving DLI (donor lymphocyte infusion)for leukemia relapse after a first allotransplant have a lower likelihood of a second relapse compared with similar patients not developing chronic GvHD. And, our previous study also reported patients with chronic GvHD after DLI was associated with a greater frequency of a negative MRD-test and lower likelihood of subsequent relapse compared with similar persons not developing chronic GvHD. Based on these data the investigators designed a randomized control study to determine whether giving additional consolidation chemotherapy and DLI might decrease likelihood of second relapse in persons without chronic GvHD or with a positive MRD-test after initial post-relapse therapy with induction chemotherapy and DLI.