Transplant Rejection

Researchers are investigating acute myocardial inflammation, a complex condition that includes acute cellular cardiac allograft rejection (ACR), cardiac sarcoidosis (CS), and immune checkpoint inhibitor induced myocarditis (ICIM). This study aims to evaluate the accuracy of [68Ga]Ga-PentixaFor PET/CT imaging for detecting inflammatory cells in these patients, offering a potentially non-invasive diagnostic option. The study is a phase 2 trial focusing on these specific heart inflammation conditions where diagnosis is currently challenging. Participants will receive an intravenous injection of a maximum of 50 micrograms of PentixaFor labeled with 150 ±15 MBq of Gallium-68 ([68Ga]) as a bolus 60 ±15 minutes before undergoing PET/CT imaging. The treatment involves this imaging procedure for all three patient groups (ACR, CS, ICIM) to assess the presence and characteristics of myocardial inflammation. During the study, researchers will evaluate imaging results by analyzing lesion number, location, and standardized uptake value (SUV) over one year. They will also monitor toxicity data for safety assessment. Participants will have regular clinical follow-ups at the cardiology department. The study involves signing informed consent and includes monitoring for any adverse effects related to the imaging agent or procedures throughout the study duration.

Researchers are evaluating the safety and effectiveness of GT729 universal cell injection for treating patients with refractory or relapsed chronic graft-versus-host disease (cGVHD) following allogeneic hematopoietic stem cell transplantation. This early phase 1 clinical trial aims to understand how this biological treatment affects people who have not responded to at least two prior systemic therapies for active cGVHD. Participants will receive the GT729 injection as the experimental treatment. The study will monitor participants from the time of infusion through 24 months to assess safety outcomes such as dose limiting toxicity within 28 days and the occurrence of adverse events. Researchers will also evaluate the overall response rate up to 6 months after the infusion. During the study, participants will undergo regular assessments including laboratory tests to monitor blood counts, liver and kidney function, and pregnancy status for women of childbearing age. Safety and treatment response will be closely observed throughout the treatment period. The total participation duration may last up to two years for long-term safety monitoring and outcome evaluation.

This research aims to understand how abnormal lipid metabolism, which is common after organ transplantation, relates to transplant rejection and failure. It focuses on cardiac transplant patients who often experience lipid changes due to immunotherapy. The study explores the interaction between PCSK9, lipid disorders, and immune responses, which may contribute to transplant rejection. The goal is to clarify these links to improve management of lipids during and after surgery. The study involves tracking heart transplant patients over a long term to observe lipid changes and their connection to rejection. It expands testing beyond traditional lipid assays to include transcriptomic, proteomic, and metabolomic analyses to better understand PCSK9's role in dyslipidemia. Single-cell sequencing is used to investigate how these lipid changes affect T-cell-mediated rejection of the transplanted heart. Participants will be followed for four years, during which blood lipid levels and graft/patient survival will be monitored. Additional assessments include measuring heart function through left ventricular ejection fraction at rest. This observational study collects detailed biological data and monitors health outcomes to deepen understanding of how lipid metabolism influences transplant success and patient survival.

Thalassemia is a common inherited blood disorder, particularly prevalent in Yunnan, China, where many patients face high treatment costs. Current treatments include blood transfusions and hematopoietic stem cell transplantation (HSCT), which can cure thalassemia but involve significant risks and complications such as organ damage and graft-versus-host disease (GVHD). This research explores a new approach called hypertransplantation, developed by Professor Ai Huisheng's team, aiming to provide a safer, more effective, and affordable treatment without the need for pre-treatment or causing GVHD. The study will test hypertransplantation, which uses hematopoietic stem cells from haplotype-compatible healthy donors without requiring pre-treatment such as chemotherapy or radiation. This innovative method relies on immune interactions between donor and recipient to achieve stable donor cell implantation. Animal studies showed promising results with no GVHD or reproductive damage, and this clinical trial plans to enroll 3 to 5 patients aged 7 to 12 years with severe Mediterranean thalassemia who are ineligible or refuse standard HSCT or gene therapy. Participants will receive the hypertransplantation treatment and be closely monitored for donor cell implantation, blood counts, hemoglobin levels, immune function, and potential complications like infections or GVHD. The primary outcome will be the donor cell implantation rate three months after transplantation, with secondary outcomes including gene carrier status after one year. The study involves a single center and a single treatment group, with follow-up assessments to evaluate safety, efficacy, and recovery of endocrine and gastrointestinal functions over time.

Researchers are conducting a prospective observational study to explore the relationship between autonomic nervous system (ANS) function and acute graft-versus-host disease (GvHD) in patients who undergo allogeneic hematopoietic stem cell transplantation. The study aims to use ANS function measurements as early tools for classification and assessment in transplant recipients. This research is led by the Institute of Hematology & Blood Diseases Hospital in China. Participants in this study are adult patients receiving HLA-haploidentical stem cell transplants. Various tests will be conducted before and after transplantation, including heart rate response to standing, piloerection tests, and dynamic electrocardiography to evaluate ANS function. These assessments take place within one month before transplantation and again between 17 to 25 days after transplantation. The study also monitors the incidence of acute GvHD, including severe cases, within 100 days after transplantation. During the study, participants will undergo scheduled evaluations to measure heart rate response, piloerection, and electrocardiography changes. Researchers will track these physiological responses to understand their association with the development of acute GvHD. The study period includes monitoring up to 100 days post-transplant to assess disease outcomes. Participants are expected to provide informed consent and comply with study monitoring requirements throughout the observation period.

Researchers are investigating a new, non-invasive method to monitor kidney function after transplantation using advanced non-contrast Magnetic Resonance Imaging (MRI). This study aims to create individualized baselines for transplanted kidneys by scanning donors before donation, allowing earlier detection of kidney problems compared to current blood tests or biopsies. It includes both donor-recipient pairs and recipients without donor data, primarily from deceased donors, to evaluate MRI's ability to track kidney health over time. Participants are divided into two main groups: one where donors undergo pre-transplant MRI to establish a personalized baseline for their kidney before transplant, and recipients are followed post-transplant to compare function against this baseline; the other group includes recipients without donor MRI data to validate MRI's standalone monitoring ability. The study also assesses body composition and metabolic health to better understand their impact on transplant kidney function. During the study, participants will undergo scheduled non-contrast MRI scans alongside clinical, laboratory, and body composition assessments. Data such as serum creatinine, eGFR, and biopsy results when available will be collected to correlate with MRI findings. The main outcome is the diagnostic accuracy of MRI for detecting transplant kidney rejection and dysfunction over up to five years. Approximately 1000 participants will be enrolled to provide robust data for developing a precise, individualized monitoring tool for kidney transplant patients.

Researchers are conducting an observational, multicenter cohort study called the SweD-HTx study, involving adult heart transplant recipients from three Swedish university hospitals. The study aims to develop a nationwide protocol for monitoring transplant rejection using donor-derived cell-free DNA (dd-cfDNA) and to better understand rejection mechanisms and immune activation. This study focuses on adults who have undergone orthotopic heart transplantation, with exclusion of those who are pregnant or have had multiple organ or stem cell transplants. Participants receive routine post-transplant care including endomyocardial biopsies at scheduled intervals. Blood samples are collected alongside these biopsies for dd-cfDNA and donor-specific antibody (DSA) analysis, using next-generation sequencing and standardized laboratory procedures. The study will analyze the relationship between dd-cfDNA levels and biopsy-confirmed rejection, following international histopathological criteria. The collection of clinical and demographic data from electronic medical records supports comprehensive analysis. Participants are monitored over several years with blood sampling coordinated with routine biopsies during the first two years post-transplant and annual data collection up to five years. Outcomes include the correlation between dd-cfDNA fraction levels and biopsy-proven rejection, longitudinal changes in dd-cfDNA and DSA, and their association. Safety and standard care continue throughout, with data securely managed and analyzed to improve rejection monitoring methods in heart transplantation.

This research investigates a new self-administered digital application designed to improve sexual health, quality of life, and psychological distress among survivors of hematopoietic stem cell transplants (HCT). HCT survivors often face long-term sexual dysfunction due to complex biological, psychological, and social factors, which significantly affect their well-being and relationships. The study aims to address these challenges through a multidisciplinary approach delivered via a digital platform. Participants will be randomly assigned to either use the SHIFT digital application or receive enhanced usual care. The SHIFT app includes interactive features like gamification, survivor videos, intimacy exercises, and optional content to engage users over eight weeks. Those in the usual care group will meet with their clinicians and may be referred to specialists if needed but will not have access to the SHIFT app. During the study, participants will complete assessments measuring sexual satisfaction, function, quality of life, anxiety, and depression at various points up to 24 weeks. Researchers will monitor global satisfaction with sex at week 8 as the primary outcome. The study involves medical evaluations and tracks psychological and physical health through questionnaires and scales, aiming to evaluate the impact of the digital intervention on sexual health outcomes and overall well-being in HCT survivors.

Researchers are evaluating axatilimab monotherapy in Chinese participants aged 12 years and older who have recurrent or refractory active chronic graft-versus-host disease (cGVHD) after receiving systemic therapy. The study aims to assess the safety, effectiveness, and pharmacokinetics of this treatment in managing cGVHD, a condition that can occur after stem cell transplantation. This is a Phase 1b/2, open-label, multicenter study sponsored by Incyte Corporation. Participants will receive axatilimab through intravenous infusion at protocol-defined doses. The study includes two parts: Part 1 focuses on safety evaluation, and Part 2 assesses efficacy. The treatment duration and dosing schedule follow the study protocol, and participants may continue to receive corticosteroids, calcineurin inhibitors, or mTOR inhibitors if stable. The study will monitor participants for up to two years and 30 days to gather information on treatment responses and adverse events. Throughout the study, participants will undergo various assessments including monitoring for treatment-emergent adverse events, evaluation of response rates, symptom improvement using the modified Lee symptom scale, and pharmacokinetic sampling for axatilimab. Additional laboratory tests will measure changes in immune markers and antibody development. Participants are expected to attend regular visits for these evaluations and safety monitoring during the study period, which may last up to two years and beyond.

Researchers are evaluating tabelecleucel, an off-the-shelf allogeneic T-cell immunotherapy, for treating Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in patients who have undergone solid organ transplant (SOT) or allogeneic hematopoietic cell transplant (HCT) and have not responded to rituximab or rituximab plus chemotherapy. This phase 3, multicenter, open-label study aims to determine the clinical benefit and safety profile of tabelecleucel in these specific patient populations. Participants are divided into cohorts based on transplant type and prior treatments: those with EBV+ PTLD after SOT who failed rituximab alone (with or without chemotherapy), and those with EBV+ PTLD after HCT who failed rituximab. Tabelecleucel is given intravenously in 5-week cycles at a dose of 2 x 10^6 cells/kg on Days 1, 8, and 15, followed by observation until Day 35. Treatment continues until maximal response, unacceptable toxicity, start of other therapy, or failure of tabelecleucel, with limits on the number of different HLA restrictions tested per cohort. Participants undergo extensive assessments including biopsy confirmation, PET-CT or MRI imaging for disease evaluation, and organ function tests. Follow-up for disease and survival status lasts up to 5 years for early enrollees and up to 12 months for others and responders. The primary outcome measured is the objective response rate, with secondary outcomes including duration of response, overall survival, and rates of graft loss or rejection. Safety and efficacy are carefully monitored throughout the study duration.