-
Pharmaceutics Jun 2024Extracorporeal photopheresis (ECP) is a therapeutic modality used for T-cell-mediated disorders. This approach involves exposing isolated white blood cells to...
Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Cutaneous T-Cell Lymphoma: A First-in-Human Phase I/II Study.
Extracorporeal photopheresis (ECP) is a therapeutic modality used for T-cell-mediated disorders. This approach involves exposing isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light, aiming to induce apoptosis in T-cells and thereby modulate immune responses. However, conventional 8-MOP-ECP lacks cell selectivity, killing both healthy and diseased cells, and has shown limited treatment efficacy. An alternative approach under investigation involves the use of 5-aminolevulinic acid (ALA) in conjunction with light, referred to as ALA-based photodynamic therapy. Our previous ex vivo studies suggest that ALA-ECP exhibits greater selectivity and efficiency in killing T-cells derived from patients with T-cell-mediated disorders compared to those treated with 8-MOP-ECP. We have conducted a clinical phase I-(II) study evaluating ALA-ECP safety and tolerability in cutaneous T-cell lymphoma (CTCL). Here, 20 ALA-ECP treatments were administered to one CTCL patient, revealing no significant changes in vital signs. Two adverse events were reported; both evaluated by the Internal Safety Review Committee as non-serious. In addition, five conceivable events with mainly mild symptoms took place. During the study period, a 53% reduction in skin involvement and a 50% reduction in pruritus was observed. In conclusion, the results indicate that ALA-ECP treatment is safe and well tolerated.
PubMed: 38931936
DOI: 10.3390/pharmaceutics16060815 -
Cancers May 2024Sézary syndrome (SS) is a rare primary cutaneous T-cell lymphoma variant. Despite various treatment options, it remains incurable, with a poor prognosis. There is an...
Sézary syndrome (SS) is a rare primary cutaneous T-cell lymphoma variant. Despite various treatment options, it remains incurable, with a poor prognosis. There is an urgent need for additional descriptive research to enhance our understanding and treatment of SS. The aim of this retrospective register-based study was to outline patients' demographic characteristics; investigate the clinical, histopathological, and molecular findings; and assess treatment effectiveness with a focus on time to next treatment (TTNT) and disease progression. Data on 17 patients with SS were obtained from the primary cutaneous lymphoma register in West Sweden between 2012 and 2024. The results revealed that not all patients exhibited the classical triad of symptoms at diagnosis, emphasizing the need for personalized diagnostic approaches. The median survival was only 2.1 years, which reflects the aggressive nature of SS. The longest median TTNT was observed in triple therapy involving retinoids, interferon alpha, and extracorporeal photopheresis (ECP). There was no significant difference in TTNT between various lines of treatment. Early initiation of ECP treatment did not result in improved outcomes. This study highlights the importance of combination therapy for improved outcomes and underscores the need for future studies to identify optimal treatment approaches.
PubMed: 38893069
DOI: 10.3390/cancers16111948 -
Transplant Infectious Disease : An... Jun 2024
PubMed: 38874266
DOI: 10.1111/tid.14320 -
The Journal of Dermatological Treatment Dec 2024Response rates of approved systemic therapies for cutaneous T-cell lymphoma (CTCL) hover near 30%, suggesting unmet need. This study describes real-world treatment...
BACKGROUND
Response rates of approved systemic therapies for cutaneous T-cell lymphoma (CTCL) hover near 30%, suggesting unmet need. This study describes real-world treatment patterns and response rates of extracorporeal photopheresis (ECP) in CTCL patients.
METHODS
A chart review was conducted in the United States of adults with CTCL who initiated ECP between January 1, 2017, and February 28, 2019, and received at least three months of ECP treatment as monotherapy or concomitant therapy. Clinical outcomes were collected quarterly for up to 18 months.
RESULTS
The 52 patients were predominantly Caucasian. Half were male; median age was 69 years. Most patients had Sézary syndrome (50%) or mycosis fungoides (36.5%). Nearly 40% of patients had stage IV disease; 33% had lymph node involvement. Nineteen patients (36.5%) achieved response (>50% reduction in BSA affected); median time to response was 6.5 months. The percentage of patients rated as at least minimally improved was 59.5% at 6 months ( = 22), 75.0% at 9 months ( = 24), and 60.0% at 12 months ( = 15) after ECP initiation.
CONCLUSIONS
Despite the ECP treated population in this study being older and having more advanced-stage disease than recent trials, response rates were comparable. These real-world findings support ECP as an effective treatment option for CTCL patients.
Topics: Humans; Photopheresis; Male; Female; Aged; Middle Aged; Lymphoma, T-Cell, Cutaneous; Skin Neoplasms; United States; Treatment Outcome; Retrospective Studies; Adult; Aged, 80 and over; Sezary Syndrome; Mycosis Fungoides; Neoplasm Staging
PubMed: 38852942
DOI: 10.1080/09546634.2024.2360568 -
Frontiers in Immunology 2024Allograft rejection is a critical issue following solid organ transplantation (SOT). Immunosuppressive therapies are crucial in reducing risk of rejection yet are... (Review)
Review
Allograft rejection is a critical issue following solid organ transplantation (SOT). Immunosuppressive therapies are crucial in reducing risk of rejection yet are accompanied by several significant side effects, including infection, malignancy, cardiovascular diseases, and nephrotoxicity. There is a current unmet medical need with a lack of effective minimization strategies for these side effects. Extracorporeal photopheresis (ECP) has shown potential as an immunosuppression (IS)-modifying technique in several SOT types, with improvements seen in acute and recurrent rejection, allograft survival, and associated side effects, and could fulfil this unmet need. Through a review of the available literature detailing key areas in which ECP may benefit patients, this review highlights the IS-modifying potential of ECP in the four most common SOT procedures (heart, lung, kidney, and liver transplantation) and highlights existing gaps in data. Current evidence supports the use of ECP for IS modification following SOT, however there is a need for further high-quality research, in particular randomized control trials, in this area.
Topics: Photopheresis; Humans; Organ Transplantation; Graft Rejection; Immunosuppression Therapy; Immunosuppressive Agents; Graft Survival
PubMed: 38846942
DOI: 10.3389/fimmu.2024.1371554 -
Journal of Clinical Apheresis Jun 2024Due to development of chronic lung allograft dysfunction (CLAD), prognosis for patients undergoing lung transplantation (LTx) is still worse compared to other solid...
BACKGROUND
Due to development of chronic lung allograft dysfunction (CLAD), prognosis for patients undergoing lung transplantation (LTx) is still worse compared to other solid organ transplant recipients. Treatment options for slowing down CLAD progression are scarce with extracorporeal photopheresis (ECP) as an established rescue therapy. The aim of the study was to identify characteristics of responders and non-responders to ECP treatment, assess their survival, lung function development and by that define the subset of patients who should receive early ECP treatment.
METHODS
We performed a retrospective study of all LTx patients receiving ECP treatment at the University Hospital Zurich between January 2010 and March 2020. Patients were followed-up for a maximum period of 5 years. Mortality and lung function development were assessed by CLAD stage and by CLAD subtype before initiation of ECP treatment.
RESULTS
Overall, 105 patients received at least one ECP following LTx. A total of 57 patients (61.3%) died within the study period with a median survival of 15 months. Mortality was 57% for patients who started ECP at CLAD1, 39% for CLAD2, 93% for CLAD3, and 90% for CLAD4 (p < 0.001). Survival and lung function development was best in young patients at early CLAD stages 1 and 2. Response to ECP treatment was worst in patients with CLAD-RAS/mixed subtype (14.3%) and patients with ECP initiation in CLAD stages 3 (7.1%) and 4 (11.1%). Survival was significantly better in a subset of patients with recurrent acute allograft dysfunction and earlier start of ECP treatment (105 vs 15 months).
CONCLUSION
In this retrospective analysis of a large group of CLAD patients treated with ECP after LTx, early initiation of ECP was associated with better long-term survival. Besides a subset of patients suffering of recurrent allograft dysfunction, especially a subset of patients defined as responders showed an improved response rate and survival, suggesting that ECP should be initiated in early CLAD stages and young patients. ECP might therefore prevent long-term disease progression even in patients with CLAD refractory to other treatment options and thus prevent or delay re-transplantation.
Topics: Humans; Photopheresis; Lung Transplantation; Retrospective Studies; Male; Female; Middle Aged; Adult; Allografts; Chronic Disease; Recurrence; Primary Graft Dysfunction
PubMed: 38829041
DOI: 10.1002/jca.22128 -
BMJ Open Respiratory Research May 2024Long-term survival after lung transplantation is limited compared with other organ transplants. The main cause is development of progressive immune-mediated damage to... (Randomized Controlled Trial)
Randomized Controlled Trial
Extracorporeal photopheresis (ECP) in the treatment of chronic lung allograft dysfunction (CLAD): a prospective, multicentre, open-label, randomised controlled trial studying the addition of ECP to standard care in the treatment of bilateral lung transplant patients with CLAD (E-CLAD UK).
BACKGROUND
Long-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 ANALYSIS
E-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 DISSEMINATION
The 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 NUMBER
EudraCT number 2022-002659-20; ISRCTN 10615985.
Topics: Adult; Female; Humans; Male; Middle Aged; Allografts; Graft Rejection; Lung; Lung Transplantation; Methoxsalen; Multicenter Studies as Topic; Photopheresis; Primary Graft Dysfunction; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome; United Kingdom
PubMed: 38724453
DOI: 10.1136/bmjresp-2023-001995 -
ImmunoTargets and Therapy 2024Hematopoietic stem cell donation is a method used to treat both blood-related and non-blood-related malignancies. Graft-versus-host disease is a potentially... (Review)
Review
Hematopoietic stem cell donation is a method used to treat both blood-related and non-blood-related malignancies. Graft-versus-host disease is a potentially life-threatening complication that can occur following a stem cell transplant from a donor. This happens after the transplanted grafts attack the recipient's body as foreign cells, causing significant morbidity and mortality. Clinically, this condition can be classified as acute or chronic based on onset and pathophysiology. This review aims to provide an overview of recent studies on extracorporeal photopheresis as a treatment strategy option for graft-versus-host-diseased patients. It will explain how it treats graft-versus-host disease, summarize its promising effects, and provide future recommendations for its use in treating this illness. Extracorporeal photopheresis is used to treat graft-versus-host disease by collecting and separating white blood cells from the patient. This blood is fractionated into different parts, and white blood cells undergo treatment with 8-methoxy psoralen, a photoactivable drug, before exposure to ultraviolet light A. Lastly, the cells that have been treated are reinfused into the recipient's body. It prompts the programmed cell death of lymphocytes and the engulfment of cellular debris by host antigen-presenting, leading to a subsequent rise in T regulatory cells. However, more experimental and randomized controlled studies are required to identify the best patient selection requirements, environments, and treatment regimens for graft-versus-host disease.
PubMed: 38689598
DOI: 10.2147/ITT.S457366 -
Journal of Clinical Apheresis Jun 2024
Topics: Humans; Male; Cell Aggregation; Citric Acid; Glucose; Photopheresis; Adult
PubMed: 38661254
DOI: 10.1002/jca.22117 -
Journal of Clinical Apheresis Jun 2024
Topics: Humans; Photopheresis; Graft vs Host Disease
PubMed: 38634471
DOI: 10.1002/jca.22115