Explore the vast range of titles available.

Extracorporeal photopheresis (ECP) is a viable treatment that slows the progression of chronic lung allograft dysfunction. Despite its immunoregulatory potential, data on extracorporeal photopheresis as an induction therapy remain rather limited. We conducted a pilot randomized controlled study on ECP as induction therapy in cystic fibrosis patients undergoing primary lung transplantation. Primary endpoints included safety, assessed based on the incidence of adverse events, treatment-related toxicity, and procedure-related complication rates; and feasibility, evaluated through the completion rate of scheduled ECP sessions, patient tolerability, and treatment discontinuation rates. Secondary endpoint consisted of an exploratory assessment of efficacy, using a composite measure that included three key components: freedom from biopsy-proven acute rejection within the first 12 months, absence of chronic lung allograft dysfunction at 36 months, and optimal graft function, defined as a predicted forced expiratory volume in the first second ≥ 90% at 36 months. Finally, exploratory endpoints included cell phenotypic and functional analyses, secreted immune protein profiling, and gene expression analysis for mechanistic insights. Patients were randomly assigned to receive either standard immunosuppressive therapy alone or standard therapy plus six sessions of extracorporeal photopheresis, with a follow-up period of 36 months. Among 36 cystic fibrosis patients who underwent lung transplantation between 2018 and 2021 and met the eligibility criteria, 21 were randomized (9 to the study group and 12 to the control group). No patients in the treatment group experienced adverse events. The enrollment rate was 61%, and the treatment discontinuation rate was 22%. The clinical composite endpoint was achieved by 28.6% of patients in the treatment group and 16.7% in the control group. Exploratory endpoint analyses revealed significant decreases in pro-inflammatory cytokines, degranulating CD8 T lymphocytes, and NK cells in the treatment group. Moreover, significant increases in Treg lymphocytes, IL-10-producing NK cells, and anti-inflammatory cytokines appeared to be associated with improved pulmonary function in the treatment group. Induction therapy with extracorporeal photopheresis is safe and feasible in lung transplantation for cystic fibrosis. Some clinical benefits appear to persist for the first 36 months of follow-up. Interestingly, a correlation between immunological modulation induced by extracorporeal photopheresis and pulmonary function was observed. https://clinicaltrials.gov/study/NCT03500575?cond=NCT03500575&rank=1, identifier NCT03500575.

Standard treatment for GVHD is glucocorticoids, but for glucocorticoid-refractory GVHD, no intervention has emerged as standard second-line treatment. This trial with 329 patients compared ruxolitinib with control (chosen from among 10 possible therapies) in patients with glucocorticoid-refractory chronic GVHD. Response at week 24 was 50% with ruxolitinib as compared with 26% with control therapy.

Chronic graft-versus-host disease (cGvHD) is a major cause of morbidity after allogeneic hematopoietic stem cell transplantation. Ruxolitinib (RUX) is a standard second-line treatment for steroid-refractory or -dependent cGvHD, while extracorporeal photopheresis (ECP), an autologous cell-based immunomodulatory procedure, is also widely used. However, comparative real-world data on combined immunomodulation with the RUX-ECP combination are scarce. We conducted a retrospective single-center analysis of patients with steroid-refractory or -dependent cGvHD receiving RUX-ECP (n=30) or ECP alone (n=21) between 2012 and 2025. The overall response rate was 77% with RUX-ECP and 52% with ECP (p=0.13), with CR rates of 17% and 10% (p=0.69). RUX-ECP was associated with a significantly shorter time to first response (2.6 vs. 12.3 months, p=0.0249). Organ-specific trends favored RUX-ECP in gastrointestinal, ocular and cutaneous cGvHD, whereas both regimens showed limited activity in pulmonary disease. Overall survival, relapse incidence and non-relapse mortality were comparable. At 12 months, complete steroid discontinuation (69% vs. 10%; p=0.005) and relative corticosteroid reduction were significantly greater with RUX-ECP (88% vs. 30%; p=0.0026). Toxicities of RUX-ECP were manageable and consistent with the known RUX profile, and several patients discontinued therapy after stable responses. Thus, combined immunomodulation with RUX-ECP showed high and fast response rates, a favorable safety profile and substantial steroid-sparing, supporting further evaluation in steroid-refractory or -dependent cGvHD patients.

Patients with steroid-refractory graft-versus-host disease (GvHD) are known to have a poor prognosis and for decades no approved drug has been available to treat this serious condition. Although ruxolitinib, a selective Janus kinase (JAK)1/2 inhibitor demonstrated significantly higher response rates in randomized trials compared to the best available therapy, and thus, is of benefit in both acute as well as chronic GvHD, there is an urgent medical need to improve results, such as durability of responses, response in eye, liver and lung manifestations and reduction of infectious complications. In this “Review” article we would like to offer strategies for improving treatment results in patients with steroid-refractory GvHD by combining ruxolitinib with extracorporeal photopheresis (ECP), a leukapheresis-based immunomodulatory treatment frequently applied in T-cell mediated immune disease including GvHD. Our article explores key published evidence supporting the clinical efficacy of both ruxolitinib and ECP in the treatment of GvHD and highlights their potentially complementary mechanisms of action.

Steroid-refractory acute graft-versus-host disease (SR-aGVHD) is a significant complication of hematopoietic stem cell transplantation (HSCT). Extracorporeal Photopheresis (ECP) represents a key second-line option. Previous reviews have provided valuable insights, and recent studies allow for an updated synthesis of efficacy, safety, and patterns of ECP use in SR-aGVHD, including outcomes not fully analysed previously. This study aims to address the literature gap by providing a comprehensive updated review of the efficacy of ECP and its patterns of use in SR-aGVHD. A Systematic literature search was conducted as per PRISMA guidelines, up to September 2024, using the PubMed, Scopus, and Cochrane databases. Studies investigating the use of ECP in the setting of chronic GVHD, GVHD prophylaxis, or first-line treatment of aGVHD were excluded. Meta-analyses using fixed and random effects models were employed to estimate the pooled effect sizes. Thirty-eight studies, including a total of 1249 participants, were included, and 29 were included in the quantitative analyses. Most studies focused on the adult population, and the majority used a retrospective single-arm study design (n = 30). Overall, skin, gut, and liver response rates were 72%, 89%, 54%, and 36%, respectively. The pooled steroid-sparing percentage was 66%. ECP showed significantly higher survival in patients with grade 2 GVHD compared with grades 3 and 4 (HR: 2.35, 95% CI: 1.67 - 3.29). ECP demonstrated a positive trend in overall survival compared to other treatments, but the results were not significant. This review indicates that ECP is an effective treatment for SR-aGVHD, with favorable response and survival outcomes. However, due to the heterogeneity observed in the analyses among the studies, more controlled trials are needed to establish its effects in combination with other agents and against other regimens. https://www.crd.york.ac.uk/prospero/, identifier CRD42024585471.

Extracorporeal photopheresis (ECP) is used by few lung transplant centers to treat chronic lung allograft dysfunction (CLAD). Although reported results suggest a beneficial effect on CLAD progression, evidence is limited to single center experiences. The aim of this study is to analyze outcomes of ECP in a large multicenter European cohort. The primary endpoint was patient survival after initiation of ECP. This study included 631 patients, 87% suffered from bronchiolitis obliterans syndrome (BOS), and 13% had restrictive allograft syndrome (RAS). Long-term stabilization was achieved in 42%, improvement in 9%, and no response in 26%. Within the first 12 months of therapy, 23% of patients died. Patients’ survival after initiation of ECP at 5 years was 56% in stable, 70% in responders, and 35% in non-responders ( p = 0.001). In multivariable Cox regression, both stabilization (HR: 0.48, CI: 0.27–0.86, p = 0.013) and response (HR: 0.11, CI: 0.04–0.35, p < 0.001) to ECP were associated with survival. Absolute FEV1 at baseline was also protective (HR: 0.09, CI: 0.01–0.94, p = 0.046). RAS phenotype was the only risk factor for mortality (HR: 2.11, 1.16–3.83, p = 0.006). This study provides long-term outcomes of ECP use in CLAD patients in the largest published cohort to date. Two-thirds of the cohort had a sustained response to ECP with excellent long-term results.

BackgroundLong-term survival after lung transplantation is limited compared with other organ transplants. The main cause is development of progressive immune-mediated damage to the lung allograft. This damage, which can develop via multiple immune pathways, is captured under the umbrella term chronic lung allograft dysfunction (CLAD). Despite the availability of powerful immunosuppressive drugs, there are presently no treatments proven to reverse or reliably halt the loss of lung function caused by CLAD. The aim of the E-CLAD UK trial is to determine whether the addition of immunomodulatory therapy, in the form of extracorporeal photopheresis (ECP), to standard care is more efficacious at stabilising lung function in CLAD compared with standard care alone.Methods and analysisE-CLAD UK is a Phase II clinical trial of an investigational medicinal product (Methoxsalen) delivered to a buffy coat prepared via an enclosed ECP circuit. Target recruitment is 90 bilateral lung transplant patients identified as having CLAD and being treated at one of the five UK adult lung transplant centres. Participants will be randomised 1:1 to intervention plus standard of care, or standard of care alone. Intervention will comprise nine ECP cycles spread over 20 weeks, each course involving two treatments of ECP on consecutive days. All participants will be followed up for a period of 24 weeks.The primary outcome is lung function stabilisation derived from change in forced expiratory volume in one second and forced vital capacity at 12 and 24 weeks compared with baseline at study entry. Other parameters include change in exercise capacity, health-related quality of life and safety. A mechanistic study will seek to identify molecular or cellular markers linked to treatment response and qualitative interviews will explore patient experiences of CLAD and the ECP treatment.A patient and public advisory group is integral to the trial from design to implementation, developing material to support the consent process and interview materials.Ethics and disseminationThe East Midlands—Derby Research Ethics Committee has provided ethical approval (REC 22/EM/0218). Dissemination will be via publications, patient-friendly summaries and presentation at scientific meetings.Trial registration numberEudraCT number 2022-002659-20; ISRCTN 10615985.

Haematopoietic stem cell transplantation (HSCT) is the treatment of choice for malignant haematological diseases. Despite continuous improvements in pre- and post-transplantation procedures, the applicability of allo-HSCT is limited by life-threatening complications such as graft-versus-host disease (GvHD), engraftment failure, and opportunistic infections. Extracorporeal photopheresis (ECP) is used to treat steroid resistant GvHD with significant success. However, the molecular mechanisms driving its immunomodulatory action, whilst preserving immune function, require further understanding. As ECP is safe to administer with few significant adverse effects, it has the potential for earlier use in the post-HSCT treatment of GvHD. Thus, further understanding the immunomodulatory mechanisms of ECP action may justify more timely use in clinical practice, as well as identify biomarkers for using ECP as first line or pre-emptive GvHD therapy. This review aims to discuss technical aspects and response to ECP, review ECP as an immunomodulatory treatment modality for chronic GvHD including the effect on regulatory T cells and circulating vs. tissue-resident immune cells and consider the importance of emerging biomarkers for ECP response.

Solid organ transplantation (SOT) faces significant challenges in managing allograft rejection, with current immunosuppressive therapies often associated with substantial adverse effects. Extracorporeal photopheresis (ECP) has emerged as a promising adjunctive treatment for rejection prevention and management in heart and lung transplants, with growing evidence supporting its use in kidney and liver transplants. Despite this, the availability of ECP and its place in standard treatment pathway is widely variable across Europe. This narrative review, supported by a European survey of 51 transplant clinicians, highlights the current usage of ECP in SOT. Findings reveal that ECP is primarily used for recurrent rejection in heart and lung transplants, with limited application currently in kidney and liver transplants. ECP has shown some efficacy in managing acute and chronic rejection, and stabilizing graft function. Barriers including lack of standardized protocols, availability of ECP, lack of high-quality clinical trial data and lack of a defined mechanism of action hinder its broader adoption. Future directions include the development of standardized protocols, multicenter registries, and further controlled clinical trials to define the role of ECP. Increased awareness, cost-effectiveness studies, mechanistic studies and equitable access are essential to integrate ECP into routine SOT management.

Extracorporeal photopheresis (ECP) is an apheresis procedure that is conventionally used as a first-line treatment for cutaneous and leukemic subtypes of T-cell lymphoma, such as Sezary’s syndrome and mycosis fungoides. Over the past three decades, its immunotherapeutic properties have been tested on a variety of autoimmune conditions, including many dermatologic diseases. There is ample evidence of ECP’s ability to modify leukocytes and alter cytokine production for certain dermatologic diseases that have been refractory to first-line treatments, such as atopic dermatitis. However, the evidence on the efficacy of ECP for the treatment of these dermatologic diseases is unclear and/or lacks sufficient evidence. The purpose of this paper is to review the literature on the utilization and clinical efficacy of ECP in the treatment of several [autoimmune] dermatologic diseases and discuss its applications, guidelines, recommendations, and future implementation for dermatologic diseases.