Graft Failure

Anterior cruciate ligament (ACL) rupture is one of the most common knee injuries, particularly in young and physically active individuals. Despite advances in reconstruction techniques, graft failure and rerupture remain clinically relevant. Revision ACL surgery is more complex than primary reconstruction and is associated with inferior outcomes, with rerupture rates of approximately 13%, reaching up to 25% when both subjective and objective failure criteria are considered. The main goal of ACL reconstruction is to restore anteroposterior and rotational knee stability, prevent secondary meniscal and cartilage damage, and enable return to sport. Surgical outcomes depend on several intraoperative factors, including graft choice and tunnel geometry, which are particularly relevant in revision settings. Diagnosis of ACL rerupture is primarily clinical, based on instability tests (Lachman, anterior drawer, pivot shift), and supported by instrumental assessment such as the KT-1000 arthrometer, which provides an objective measure of joint laxity. Revision ACL reconstruction can be performed using different surgical techniques (single-bundle, double-bundle, or combined extra-articular procedures) and graft types (autograft or allograft). Surgical strategy depends on multiple factors such as meniscal and cartilage status, previous surgery characteristics, tunnel positioning/enlargement, and fixation devices. However, no consensus exists regarding the optimal approach in terms of mid- to long-term outcomes. A major long-term complication is the development of osteoarthritis, particularly in this typically young and active patient population. Identification of modifiable factors, such as surgical technique and graft type, may help reduce failure risk and joint degeneration. This study aims to evaluate clinical and radiographic outcomes over a follow-up period exceeding two years in patients undergoing revision ACL reconstruction with different surgical techniques and graft types. The study also integrates objective knee laxity assessment using KT-1000 and markerless motion analysis based on artificial intelligence. Functional movements are recorded via video and analyzed using Sports2D software, enabling 2D kinematic analysis without markers or sensors, providing quantitative functional data to complement clinical and radiographic evaluation.

This trial will determine whether adding ruxolitinib to a reduced intensity conditioning (RIC) regimen reduces the rate of graft failure following haploidentical (haplo) hematopoietic cell transplant (HCT) for children and young adults with sickle cell disease (SCD). This study will enroll and treat up to 24 participants. Recruitment is expected to last for about 2 years and participants will be followed for an additional 2 years post-HCT.

A single center, open label, interventional, phase II trial for donor transplant for high risk hemoglobinopathies and other red cell transfusion dependent disorders utilizing allogeneic hematopoietic stem cell transplantation (HSCT) regimens.

Coronary artery bypass graft (CABG) surgery is the commonest type of heart operation performed. During this, arteries or veins (termed 'grafts') are used to supply blood around blockages within the blood vessels that supply the heart. Unfortunately, these grafts can sometimes fail, and patients can also experience complications like heart attacks and strokes, after surgery. It is known that vein grafts are more likely to narrow over time. Additionally, treating vein graft failure is very challenging, as repeat surgery is riskier and procedures to stent open the veins can also fail. However, it is not fully understood why these complications occur. In this study, the investigators will use an imaging technique called a total-body Positron Emission Tomography (PET) scan. This uses special radioactive dyes (radiotracers) to look at what is happening inside vein grafts. With this technique, the investigators will also be able to see what is happening to the heart, brain and wider parts of the body after CABG surgery. This study will aim to recruit 70 participants in total (maximum 150). 40 (maximum of 120) of these participants will have recently undergone CABG surgery and received ≥1 vein graft. The remaining 30 will have undergone CABG surgery ≥5 years ago and will have symptoms suggestive of vein graft failure. The study will last a total of 36 months and will involve participants undertaking the following assessments: 1. Total-body Positron Emission Tomography and Computed Tomography (PET-CT) scan 2. Ultrasound scan of the heart (echocardiogram) 3. A blood test - up to four tablespoons (60 mL) of blood will be taken for immediate testing and the remainder will be stored for future ethically approved studies.

The investigators hypothesize that graft rejection after hematopoietic stem cell transplant (HSCT) is primarily driven by interferon gamma, and prophylactic interferon gamma inhibition in high-risk patients will prevent graft rejection. Additionally, knowledge of emapalumab PK/PD and in vitro mechanistic effects of emapalumab in this novel setting will guide optimization of dosing regimens and treatment approaches in future studies.

The goal of this pilot trial is to to evaluate the preliminary effect of oral colchicine therapy on graft outcomes in patients underwent primary isolated CABG. The main questions it aims to answer is: 1. Whether the oral colchicine therapy may reduce the failure outcome of grafts after CABG. 2. Whether it is feasible to construct a muticenter powered trial to test the superiority hypothesis. Researchers will compare colchicine to none to see if colchicine works. Participants will 1. Take oral colchicine (0.5mg daily) therapy for 12 months after CABG. 2. Clinical follow-up at Month 1, 6, and 12 after CABG. 3. Protocol-driven CCTA at Week 1 and Month 12 after CABG.

The use of a graft from the left internal thoracic artery to the left anterior descending artery has become the gold standard for the indication of coronary artery bypass grafting. However, choosing a graft for the second-best coronary artery, focusing on long-term patency, is still a challenge. The saphenous vein using the "no-touch" technique is an alternative to a radial artery graft, but there is little evidence, especially in women. This randomized clinical study aims to compare the patency of these grafts in the second-best coronary artery in women undergoing coronary artery bypass grafting.

The proposed trial is a single arm, non-randomized, single center pilot study utilizing CliniMACS CD34 Reagent System for patients following allogeneic hematopoietic stem cell transplant (HSCT) requiring treatment of graft dysfunction or failure.

Acute rejection after kidney transplantation should ideally be diagnosed prior to immunologic injury in a non-invasive fashion in order to improve long-term graft function. Donor-derived cell-free DNA (ddcfDNA) is a promising method to do so as it is elevated prior to acute rejection and has good predictive performance especially for antibody-mediated and high severity T-cell mediated rejection. Its ability to predict low severity T-cell mediated rejection and future graft function remains equivocal. Regulatory T cells (Tregs) are essential in transplant tolerance by suppressing effector immune responses. Circulating post-transplant highly suppressive HLA-DR+ Tregs were reduced in recipients who developed acute rejection. Preliminary results in a cohort including predominantly low severity T-cell mediated rejection also showed that pre-transplant circulating highly suppressive TNFR2+ Tregs were reduced in and could predict acute rejection. Integrating dd-cfDNA with HLA-DR+TNFR2+ Treg could improve the predictive performance for acute rejection especially of low severity and potentially predict graft function. Plasma dd-cfDNA and HLA-DR+TNFR2+ Tregs will be measured in 150 kidney transplant recipients at scheduled intervals during the first 6 months post-transplant. Predictive accuracy of a model integrating ddcfDNA and HLA-DR+TNFR2+ Treg for acute rejection will be tested using ROC curve analysis and multivariate logistic regression. Predictive accuracy for 1-year graft function will be tested using multivariate linear regression. High predictive performance for acute rejection and graft function using a model integrating dd-cfDNA and HLA-DR+TNFR2+ Treg would help identify kidney transplant recipients at immunologic risk early on and allow personalization of immunosuppression accordingly.

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. We previously reported encouraging results with a novel Flu/Cy regimen. However, there are still around 20% patients developed delayed platelet recovery. We designed a modified regimen to further improve the hematopoietic reconstitution after second transplantation. This prospective, single-arm study aims to investigate the safety and efficacy of this modified regimen.

The goal of this clinical trial is to compare the degree of HLA sensitization at 2 years in patients with late renal graft failure (\> 3 months) when receiving reduced immunosuppressant treatment versus stopping immunosuppression at 6 months. The main question this study aims to answer is: Does maintaining long-term immunosuppression in patients with a late renal graft failure (\> 3 months) safely reduce the risk of HLA sensitization? To answer this question, patients will be assigned to a control arm or investigational arm: * Patients assigned to the control arm will receive standard treatment, in which immunosuppressant treatment is withdrawn after 6 months. * Patients assigned to the investigatonal arm will continue immunosuppressant treatment at low doses for 2 years. Patients recruited in this clinical trial will be followed for up to 2 years. During this time, patients will visit the clinic every 3 months for checkups and tests.

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. There are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). However, the study was performed in single-center and with very small sample size. Therefore, it should be further validated via multicenter study. In this multi-center study, we aim to further evaluate the safety and efficacy of this protocol.

This is a multi-center, observational cohort study including patients with prior coronary artery bypass grafting (CABG) and ≥1 saphenous vein grafts (SVG) presenting with recurrent ischemic symptoms. Objective: to investigate the clinical outcomes in patients with prior CABG evaluated for bypass graft failure and progression of native coronary artery disease (CAD). Follow-up will be collected through national registry databases, electronic medical patient records and standardized telephonic assessment at 3 and 5 years follow-up.

Despite progress in chemotherapy, targeted therapy and immunotherapy, allogeneic hematopoietic stem cell transplantation (allo-SCT) is still the only curative procedure for some hematological malignancies. The probability of finding a matched sibling donor (MSD) is estimated under the classical 30%, because of the age of patients and their relatives, and a matched unrelated donor (MUD) can take time to identify. Currently in France, 25% of the allo-SCT are performed with an haplo-identical related donor. The Baltimore group developed an approach using haploidentical related donors, RIC, T-replete bone marrow and post-transplant high dose cyclophosphamide (PTCy) in patients with advanced hematological malignancies. PTCy has shown to eradicate alloreactive donor and host T-cells, activated by respective antigens, thereby reducing the incidence of graft versus host disease (GvHD) but delaying hematopoietic recovery. Therefore, the main source of graft is peripheral blood stem cells (PBSC) mobilized by G-CSF in France. Unfortunately, with PBSC we observe a higher cumulative incidence of GvHD (around 50%) and a higher toxicity-related mortality (TRM), especially for recipients \>50 years old. The co-transplantation of Mesenchymal Stem Cells (MSC) at the time of transplantation has previously shown a double interest in GvHD immunomodulation and hematopoiesis support. Pre-clinical studies (in mice) have shown that mesenchymal stromal cells (MSCs) from Wharton's Jelly reduce the incidence of GvHD when the infusions are weekly repeated. We propose a phase I clinical trial to find the maximum tolerated dose (MTD) of a weekly infusion of WJ-MSC administered as GvHD prophylaxis and as a support for a faster hematological reconstitution after haplo-identical allo-SCT.

Prognosis of patients with graft failure is dismal, and re-transplantation is the sole option for long-term survival. Currently, there is no consensus concerning therapeutic options in patients with primary or secondary (within the 60 days post-transplantation) graft failure and finding a new donor within an acceptable delay is challenging. Literature is poor on the subject while the overall survival of such patients is about 30% at 1 year. This situation thus represents today a very challenging unmet medical need. Recently, haploidentical (haplo) related donor Stem Cell Transplantation (haplo-SCT) have improved dramatically outcomes using T-cell replete grafts with administration of post-transplantation cyclophosphamide (PTCy, which targets alloreactive T cells generated early after an HLA-mismatched transplant, sparing regulatory T cells and leaving unaffected the non-dividing hematopoietic stem cells) and standard post-transplant immune suppression with a calcineurin inhibitor (CNI) and mycophenolate mofetil. Our group re-transplanted a patient who experienced two consecutive graft failures and was successfully managed through a third haplo-SCT from her son using PTCy. We then retrospectively collected and analyzed data from 26 primary graft failure patients transplanted between 2011 and 2017 in 15 centers on behalf of French Society for Stem Cell Transplantation and Cell Therapy (SFGM-TC). The study population consisted mainly of patients with primary or secondary (within the 60 days post-transplantation) graft failure who underwent haplo-SCT and received PTCy as graft-versus-host-disease prophylaxis. The 1-year overall survival was about 60% suggesting that this approach might be a valid option in this particular poor clinical situation but now need validation through a phase II multicenter, national, prospective cohort study.

SENIOR transplant Registry European transplant registry of senior renal transplant recipients (above the age of 65 years) receiving initial immunosuppression with tacrolimus once daily, mycophenolate and steroids to investigate long term outcomes on an observational basis.