Multiple Locations, United Kingdom

Tissue Immune Landscape of Graft Versus Host Disease After Allogeneic Stem Cell Transplantation (TIL-GVHD)

Context : Chronic Graft versus Host Disease (cGVHD) represents the main cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (alloSCT), occurring in 30 and 60%. Translational studies showed that different alloreactive T cell subsets were involved and associated with cGVHD, and regulatory subsets were deficient. Several homeostatic abnormalities of B cell subsets were also shown, which, in the context of high BAFF level, contributed to autoreactive B cell clone emergence. In alloSCT patients, we observed (Forcade et al, Blood 2016) in the blood, a T cell subset called TFH, with B cell help capacity, similar to germinal center reaction. During cGVHD, blood TFH were highly activated, skewed toward a Th1/Th17 profile, and presented enhanced capacity to provide " help " to B cells, promoting auto-/allo-antibody production in the context of cGVHD. This was associated with increased level of CXCL13 in such patients, suggesting homing of this subset to lymphoid tissues. Liarski et al (Sci Trans Med 2014) showed that TFH were observed in inflamed tissue sample from patients with lupus, and demonstrated close interaction with B cells, mimicking germinal center structures, such as tertiary lymphoid organs. Preliminary data, on cGVHD tissue target, showed a CD4+ T cell infiltrate, of which some expressed CXCR5, ICOS, PD1 in single staining. Hypothesis : cGVHD target tissue contains tertiary lymphoid structures.

Prevention of Severe Acute Graft-versus-host Disease in Pediatric Patients Using a daGOAT Model

This study aims to prospectively evaluate the use of the daGOAT model in real-world clinical settings at the Institute of Hematology, Chinese Academy of Medical Sciences (IHCAMS).

Efficacy and Safety of Low-dose Ibrutinib and Itraconazole in Chronic Graft Versus Host Disease

In this phase 2 clinical trial, patients with newly diagnosed cGVHD and refractory cGVHD will receive low-dose ibrutinib (140mg/day) combined with a cytochrome 3A4 inhibitor (itraconazole, 100mg BID) for six months. The follow-up consists of weekly visits for the first months and then monthly for six months. The investigators will address clinical and biochemical parameters in each visit and grade severity using the NIH (2014) scale. Also, patients will answer the modified Lee symptom scale, and grade response to treatment using the National Institutes of Health (NIH) Consensus Panel Chronic GVHD Activity Assessment (2014). The investigators will grade adverse events with the Common Terminology Criteria for Adverse Events [v5.0]. The investigators will report proportion and time to any response, complete response, partial response, stable disease, and progression. Also, the investigators will report the proportion of patients that interrupted steroids for at least one month, the proportion of patients that interrupted every immunosuppressive therapy for at least one month, and the proportion of patients that interrupted ibrutinib specifying the cause of the interruption.

Human Amniotic Epithelial Cells Prevent Acute Graft-versus-host Disease After Hematopoietic Stem Cell Transplantation

A dose escalation study evaluating the safety and efficacy of human amniotic epithelial cells( hAECs) in preventing acute graft-versus-host(aGVHD) disease after hematopoietic stem cell transplantation(HSCT). The doses were 1×10^6、2×10^6、5×^6 cell/kg, successively.

Sitagliptin for the Treatment of Grade 3-4 and Refractory Acute Graft-versus-host Disease

The prognosis of severe (grade 3-4) and steroid refractory acute GVHD continues to be dismal. Sitagliptin given as GVHD-prophylaxis has recently been shown to reduce the incidence of acute GVHD to less than 10% with an excellent safety profile. In this single center and single arm phase 2 study we aim to explore the safety and efficacy of sitagliptin in the treatment of severe and refractory acute GVHD. Patient with new onset grade 3-4 acute GVHD will receive standard treatment consisting CNI and methylprednisolone 1-2 mg/kg/day or an equivalent dose of prednisone. Patients with refractory grade 2-4 acute GVHD will continue their current treatment; however methylprednisolone dose will be reduced to ≤ 1 mg/kg/day or an equivalent dose of prednisone. Oral sitagliptin will be commenced at a dose of 100 mg BID. The dose will be increased by 100 mg every three days up to a maximal dose of 300 mg BID. In the case of significant drug related side effects or drug intolerance, the last tolerated dose will be resumed. Patients responding well to lower doses of sitagliptin, will not be given higher doses of the drug. Sitagliptin will be provided as long as deemed effective by the treating physician up to three months. The primary end point will be the proportion of patients achieving CR, VGPR or PR by day 28. The secondary endpoints will be safety profile, proportion of patients achieving CR, VGPR or PR by day 56, 6-month duration of response (time from first response to GVHD progression or death), proportion of patients discontinuing immunosuppressive treatment by 3 and 6 months, proportion of patients developing chronic GVHD (limited and extensive) by 6 months, time to response, specific organ response, biomarker profile (ST2 and REG3a), Infection profile, OS at 6 months, GVHD free - disease free survival at 6 months.

Prevention of Acute Graft Versus Host Disease in Patients Undergoing Allogeneic ApoGraft Stem Cell Transplantation

ApoGraft product is a mobilized peripheral blood cell product of a matched Related donor, collected via apheresis, which is exposed to the apoptotic mediator Fas Ligand (CD95L) prior to transplantation (Ex Vivo). The study is designed to address the aspects of engraftment and Prevention of Acute Graft versus Host Disease (aGvHD) rate and/or severity in 12 Patients STUDY DESIGN: This is a phase 1/2, open-label, proof-of-concept, staggered 4-cohort clinical study. Each cohort will include 3 patients with hemato-oncology disorders eligible for allogeneic HLA-matched HSCT. Patients in all cohorts will undergo similar study procedures and evaluation. The cohorts will differ from each other in the amount of apoptotic mediator Fas Ligand (APO010) to which the graft is exposed during incubation prior to ApoGraft transplantation and HSCT, ranging from 10 ng/ml APO010 in Cohort 1, 25 ng/ml APO010 in Cohort 2, 50 ng/ml APO010 in Cohort 3 and 100 ng/ml APO010 in Cohort 4. APO010 is washed-out as part of the ApoGraft process and only trace amounts of APO010 are present in the final ApoGraft product The study consists of a screening phase (subject and donor clinical assessment and screening tests), transplantation of ApoGraft, and a follow-up period of 180 days during and after hospitalization. The study will progress from one cohort to the next based on an independent data safety monitoring board (DSMB) review and analysis of safety data

A Study to Evaluate Vimseltinib in Adults With Active Chronic Graft-Versus-Host Disease (cGVHD)

Treatment of Oral Chronic Graft-versus-host Disease With Human Umbilical Cord Mesenchymal Stem Cell Dressing

Fecal Microbiota Transplant and Dietary Fiber Supplementation for the Treatment of Gut Graft Versus Host Disease

OUTLINE: Patients are randomized to 1 of 4 arms. ARM I: Patients receive upper FMT capsules orally (PO) over 5 days or via post-pyloric or nasogastric (NG) feeding tube over 2 days. ARM II: Patients undergo lower FMT via colonoscopy on day 0. ARM III: Patients receive upper FMT capsules PO over 5 days or via post-pyloric or NG feeding tube over 2 days. Patients also receive fiber supplementation PO or via post-pyloric or NG feeding tube from the first day of FMT administration and up to 6 weeks post FMT. ARM IV: Patients undergo lower FMT via colonoscopy on day 0. Patients also receive fiber supplementation PO or via post-pyloric or NG feeding tube from day 0 up to 6 weeks post FMT. Patients also undergo tissue, stool, stool swabs, and blood sample collection throughout the study. After completion of study treatment, patients are followed up for 365 days.

Umbilical Cord Mesenchymal Stem Cells in the Treatment of Moderate/Severe Chronic Graft-versus-host Disease

Chronic graft-versus-host disease (cGVHD) refers to the clinicopathological synthesis of lymphocytes from the donor attacking the recipient's organs during the process of rebuilding the donor's immunity after allogeneic hematopoietic stem cell transplantation (allo-HSCT) Signs (including classic cGVHD and overlap syndrome) are one of the main complications after transplantation, with an incidence of 30% to 70%. cGVHD is a systemic disease with multi-system damage similar to autoimmune and other immune diseases. It can affect multiple organs such as skin, liver, kidney, and peripheral nerves, causing a serious decline in the quality of life of patients, and death in the late stage of transplantation. main reason. According to the cGVHD prognostic risk scoring system (revised Risk Group) revised by the European Society for Blood and Bone Marrow Transplantation (EBMT) in 2017, the 3-year survival rate of patients with rRG1 (0-3 points) is about 93.3 ± 6.4%, and rRG2 (4-6 points) About 84.9 ± 3.4%, rRG3 (7-9 points) about 70.9 ± 4.4%, rRG4 (≥10 points) about 32.0 ± 1.1%, it can be seen that moderate to severe cGVHD directly affects the survival of allo-HSCT patients. Once moderate or severe cGVHD is diagnosed, glucocorticoids with or without calcineurin inhibitor (CNI) are first-line drugs, but the effective rate is less than 50%, and the prognosis of hormone-resistant severe cGVHD is extremely poor even if second-line treatment is added. Second-line treatments include monoclonal antibodies, immunosuppressants, chemotherapy drugs, phototherapy or others. Most of them cannot improve the long-term survival rate. The main reason is that these treatments suppress immunity for a long time, which increases the risk of infection and reduces the survival rate. In this context, the treatment of mesenchymal stromal stem cells (MSCs) provides a new path for clinical treatment of cGVHD. In 2002, Frassoni reported for the first time that MSCs expanded in vitro were used to evaluate the efficacy of allo-HSCT. Allo-HSCT transplanted patients with hematological malignancies were enrolled. MSCs were derived from the donor's bone marrow. After expanded in vitro, participants were combined with the donor's hematopoietic stem cells for reinfusion. As a result, the incidence of aGVHD in the MSCs expansion group and cGVHD within 6 months was significantly lower in the control group, the 6-month OS was significantly higher than that in the control group, and there was no significant difference in the recurrence rate. Subsequently, in 2004, Le Blanc and others successfully used third-party MSCs to successfully treat a refractory grade IV intestinal combined with liver aGVHD for the first time. Subsequently, MSCs were increasingly used in clinical studies for the treatment of GVHD. More clinical trials have shown that umbilical cord-derived MSCs cultured in vitro can not only promote the implantation of hematopoietic stem cells (HSC), but also reduce the incidence of severe GVHD in patients, showing a good therapeutic effect.