Complement and Graft-versus-host Disease
Allografted With Myeloablative ConditioningAllogeneic haematopoietic stem cell transplantation (HSCT) often remains the only curative treatment for haematological malignancies. The anti-leukaemic effect of allogeneic HSCT, called the GvL (Graf-versus-Leukemia) effect, is often associated to the development of an immune response against healthy recipient cells leading to a graft-versus-host disease (GvHD) in 20 to 70% of allogeneic HSCT. Acute GvHD, that usually targets the skin, the gastrointestinal (GI) tract and the liver, is an important cause of morbidity and mortality after allogeneic HSCT, particularly in the case of GI GvHD. The main goal of the research in the field of allogeneic HSCT is to determine strategies that could decrease the risk of GvHD without affecting the GvL effect. According to GVHD experimental models, it is likely that GvL but not GvHD may occur in the absence of inflammatory signals induced by the transplant-associated conditioning. Based on this hypothesis, we have chosen to analyse the role of Complement system in patients who received allogeneic HSCT. Indeed, Complement system is a major actor of inflammation and in the generation of tissue destruction, both of which are involved in the physiopathology of GVHD. Furthermore, it might be a potential target of some available inhibitory drugs (purified C1-Inhibitor, anti-C5 antibodies) in a preventive or curative manner in such patients. Preliminary data obtained from 34 allografted patients in our institution suggest that Complement activation by the classical pathway is correlated to the occurrence of GI GVHD. The goal of our current project, in order to confirm these preliminary results in a larger series, is to explore Complement system activation in patients who received allogeneic HSCT in three Adult Hematology departments in Paris fot two years and to correlate the biological results to the clinical events occurring after HSCT.
Bortezomib Plus Tacrolimus and Methotrexate to Prevent Graft Versus Host Disease (GVHD) After Mismatched...
Hematologic MalignanciesThe purpose of this study is to determine if Velcade (also known as bortezomib) can help prevent graft versus host disease (GVHD) developing after transplantation. This is done by using a combination of three immune suppressive medications: Velcade, tacrolimus and methotrexate. Stem cell transplantation is one of the options for patients with cancer of the blood or blood forming organs. Recently, allogeneic stem cell transplants have been performed using lower doses of chemotherapy and radiotherapy: non-myeloablative or "mini" transplants. GVHD is a significant problem that may occur even after "mini" transplantations. Information from other research studies, suggests that Velcade may help to reduce the risk of developing GVHD when given early after transplantation.
Infliximab for the Prevention of Graft-versus-Host Disease Following Allogenic Hematopoietic Stem...
Graft-Versus-Host DiseaseThis study will evaluate the efficacy of infliximab in reducing the incidence of grade II-IV acute graft versus host disease by day +100 post-transplant in patients undergoing allogeneic hematopoietic stem cell transplant.
Sirolimus With Tacrolimus for Graft-vs-Host Disease Prophylaxis After Un-Related Stem Cell Transplantation...
Acute Myelogenous LeukemiaGraft Versus Host Disease5 moreThe purpose of this study is to evaluate the ability of sirolimus to prevent graft versus host disease (GVHD) in patients following stem cell transplant from an unrelated donor. This trial is designed to test the hypothesis that elimination of methotrexate in the unrelated donor group would lead to less transplant-related toxicity while still preserving the effective control of GVHD.
Evaluation of a Kit for the Prediction of the Risk of Graft Versus Host Disease
HemopathyThis study is a proof of concept that will assess the Predictor's kit performances. The test will be performed by several technicians, in immunological laboratories of several sites in France. In this study, "couples" of donor / recipient in the frame of a graft of CSH will be included.
Polyomic Biomarker Verification in Adult Chronic Graft-Versus-Host Disease (ABLE3.0/CTTC2201)
Chronic Graft-versus-Host-DiseaseAllogeneic Hematopoietic Stem Cell Transplantation3 moreChronic graft-versus-host disease (cGvHD) is one of the most serious complications following BMT (Bone Marrow Transplantation). cGvHD occurs when donor immune cells "attack" the tissues and organs of the person receiving the BMT. cGvHD can be difficult to treat once it is established leading to poor quality of life for recipients of a BMT. The goal of this study is to determine if, by using biomarkers, the investigators can predict which patients are at the highest risk of developing cGvHD after BMT, before cGvHD develops. The ABLE3.0 / CTTC 2201 study will validate and potentially refine the initial predictive biomarker algorithm developed from the original ABLE/PBTMC 1202 study (ABLE1.0), allowing clinicians the ability to pre-emptively predict their patient's future risk of developing both late-acute and chronic GvHD. This will provide the foundation for the later development of clinical trials aimed at reducing immune suppression quicker after transplant for low-risk patients (<10% risk) and justifying more intensive approaches such as pre-emptive treatments before the onset of chronic GvHD in high-risk patients (>45% risk).
The Skin Microbiome in Graft Versus Host Disease
Skin MicrobiomeGraft Versus Host Disease1 moreBased on the evidence on the impact of the intestinal microbiome on the Graft Versus Host Disease (GVHD) after allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT), it is hypothesized that the skin-microbiome may play a role in cutaneous GVHD as well. Therefore, this study aims at investigating the skin-microbiota of patients with GVHD after allo-HSCT and of patients without GVHD after allo-HSCT.
Gluten Free Diet in Preventing Graft Versus Host Disease in Patients Undergoing Donor Stem Cell...
Graft Versus Host DiseaseHematopoietic Cell Transplantation RecipientThis pilot clinical trial studies how well a gluten free diet works in preventing graft versus host disease in patients who are undergoing a donor stem cell transplant. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft versus host disease). A gluten free diet may decrease intestinal inflammation and graft versus host disease in patients who are undergoing a donor stem cell transplant.
Safety Follow-up of Treatment With Remestemcel-L in Pediatric Participants Who Have Failed to Respond...
Grade B Acute Graft Versus Host DiseaseGrade C Acute Graft Versus Host Disease1 moreOngoing safety assessment follow-up to Protocol MSB-GVHD001 (NCT02336230) of remestemcel-L treatment in pediatric participants with acute graft versus host disease (aGVHD), following allogeneic hematopoietic stem cell transplant (HSCT), that have failed to respond to treatment with systemic corticosteroid therapy.
Pharmacokinetics of Micafungin Given Twice Weekly Intravenously Compared to Micafungin Given Daily...
Acute Graft Versus Host Disease Grade II-IVAllogeneic Stem Cell Transplant2 moreThe primary objective of this trial is as follows: To determine the pharmacokinetics of micafungin given twice weekly in patients at risk for developing an invasive fungal disease (patients who are being treated for acute or chronic graft versus host disease; patients receiving reduced intensity conditioning for Stem Cell Transplant (SCT); receiving first remission induction chemotherapy for Acute Myeloid Leucaemia (AML)/MyeloDysplasticSyndrome (MDS)) compared to the pharmacokinetics of micafungin given daily. The secondary objective of this trial is as follows: To determine whether adequate exposure of micafungin is attained. To determine the safety of micafungin in this patient population