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Transplantation and Cellular Therapy Sep 2023Graft-versus-host disease (GVHD) is a major cause of mortality and morbidity following allogeneic hematopoietic stem cell transplantation. Extracorporeal photopheresis... (Review)
Review
Graft-versus-host disease (GVHD) is a major cause of mortality and morbidity following allogeneic hematopoietic stem cell transplantation. Extracorporeal photopheresis (ECP), which exposes mononuclear cells to ultraviolet A irradiation in the presence of a photosensitizing agent, has shown efficacy in the treatment of GVHD. Recent observations in molecular and cell biology have revealed the mechanisms by which ECP can reverse GVHD, including lymphocyte apoptosis, differentiation of dendritic cells from circulating monocytes, and modification of the cytokine profile and T cell subpopulations. Technical innovations have made ECP accessible to a broader range of patients; however, logistical constraints may limit its use. In this review, we scrutinize the development of ECP from its origins to recent insights into the biology underlying ECP efficacy. We also review practical aspects that may complicate successful ECP treatment. Finally, we analyze how these theoretical concepts translate into clinical practice, summarizing the published experiences of leading research groups worldwide.
Topics: Humans; Photopheresis; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Monocytes; Transplantation, Homologous
PubMed: 37419324
DOI: 10.1016/j.jtct.2023.07.001 -
The European Respiratory Journal Mar 2024Chronic graft--host disease (cGvHD) is a common complication after allogeneic haematopoietic stem cell transplantation, characterised by a broad disease spectrum that...
Chronic graft--host disease (cGvHD) is a common complication after allogeneic haematopoietic stem cell transplantation, characterised by a broad disease spectrum that can affect virtually any organ. Although pulmonary cGvHD is a less common manifestation, it is of great concern due to its severity and poor prognosis. Optimal management of patients with pulmonary cGvHD is complicated and no standardised approach is available. The purpose of this joint European Respiratory Society (ERS) and European Society for Blood and Marrow Transplantation task force was to develop evidence-based recommendations regarding the treatment of pulmonary cGvHD phenotype bronchiolitis obliterans syndrome in adults. A multidisciplinary group representing specialists in haematology, respiratory medicine and methodology, as well as patient advocates, formulated eight PICO (patient, intervention, comparison, outcome) and two narrative questions. Following the ERS standardised methodology, we conducted systematic reviews to address these questions and used the Grading of Recommendations Assessment, Development and Evaluation approach to develop recommendations. The resulting guideline addresses common therapeutic options (inhalation therapy, fluticasone-azithromycin-montelukast, imatinib, ibrutinib, ruxolitinib, belumosudil, extracorporeal photopheresis and lung transplantation), as well as other aspects of general management, such as lung functional and radiological follow-up and pulmonary rehabilitation, for adults with pulmonary cGvHD phenotype bronchiolitis obliterans syndrome. These recommendations include important advancements that could be incorporated in the management of adults with pulmonary cGvHD, primarily aimed at improving and standardising treatment and improving outcomes.
Topics: Adult; Humans; Bronchiolitis Obliterans Syndrome; Graft vs Host Disease; Lung; Hematopoietic Stem Cell Transplantation; Lung Transplantation; Chronic Disease
PubMed: 38485149
DOI: 10.1183/13993003.01727-2023 -
International Journal of Molecular... Mar 2024Extracorporeal photopheresis (ECP) is an apheresis procedure that is conventionally used as a first-line treatment for cutaneous and leukemic subtypes of T-cell... (Review)
Review
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.
Topics: Humans; Photopheresis; Skin Neoplasms; Mycosis Fungoides; Blood Component Removal; Sezary Syndrome
PubMed: 38474257
DOI: 10.3390/ijms25053011 -
Pharmacological Reviews Nov 2023Chronic lung rejection, also called chronic lung allograft dysfunction (CLAD), remains the major hurdle limiting long-term survival after lung transplantation, and... (Review)
Review
Chronic lung rejection, also called chronic lung allograft dysfunction (CLAD), remains the major hurdle limiting long-term survival after lung transplantation, and limited therapeutic options are available to slow the progressive decline in lung function. Most interventions are only temporarily effective in stabilizing the loss of or modestly improving lung function, with disease progression resuming over time in the majority of patients. Therefore, identification of effective treatments that prevent the onset or halt progression of CLAD is urgently needed. As a key effector cell in its pathophysiology, lymphocytes have been considered a therapeutic target in CLAD. The aim of this review is to evaluate the use and efficacy of lymphocyte depleting and immunomodulating therapies in progressive CLAD beyond usual maintenance immunosuppressive strategies. Modalities used include anti-thymocyte globulin, alemtuzumab, methotrexate, cyclophosphamide, total lymphoid irradiation, and extracorporeal photopheresis, and to explore possible future strategies. When considering both efficacy and risk of side effects, extracorporeal photopheresis, anti-thymocyte globulin and total lymphoid irradiation appear to offer the best treatment options currently available for progressive CLAD patients. SIGNIFICANCE STATEMENT: Effective treatments to prevent the onset and progression of chronic lung rejection after lung transplantation are still a major shortcoming. Based on existing data to date, considering both efficacy and risk of side effects, extracorporeal photopheresis, anti-thymocyte globulin, and total lymphoid irradiation are currently the most viable second-line treatment options. However, it is important to note that interpretation of most results is hampered by the lack of randomized controlled trials.
Topics: Humans; Antilymphocyte Serum; Bronchiolitis Obliterans; Graft Rejection; Lung; Allografts; Lymphocytes; Chronic Disease
PubMed: 37295951
DOI: 10.1124/pharmrev.123.000834 -
Hematological Oncology Dec 2023Patients with cutaneous T-cell lymphoma with progressive disease typically undergo a series of skin-directed and systemic therapy regimens during cycles of response and... (Review)
Review
Patients with cutaneous T-cell lymphoma with progressive disease typically undergo a series of skin-directed and systemic therapy regimens during cycles of response and relapse. Extracorporeal photopheresis (ECP) is an effective and safe systemic treatment option, often reserved for later stages of disease and typically employed after failure of several other therapies. ECP has benefits in response rate, time to next treatment, and tolerability that may support its use earlier in the treatment cycle for advancing/progressing disease.
Topics: Humans; Photopheresis; Mycosis Fungoides; Skin Neoplasms; Neoplasm Recurrence, Local; Lymphoma, T-Cell, Cutaneous
PubMed: 37974524
DOI: 10.1002/hon.3229 -
Dermatologie (Heidelberg, Germany) Jul 2023Guidelines are systematically developed decision-making aids to ensure appropriate clinical care for specific medical conditions. In Germany, dermatological guidelines... (Review)
Review
Guidelines are systematically developed decision-making aids to ensure appropriate clinical care for specific medical conditions. In Germany, dermatological guidelines are developed under the aegis of the German Dermatological Society (DDG) and the Professional Association of German Dermatologists (BVDD), while European and international guidelines are published by organisations such as the European Centre for Guidelines Development (EuroGuiDerm), founded by the European Dermatology Forum (EDF) in cooperation with the Division of Evidence-Based Medicine at Charité-Universitätsmedizin Berlin. In 2021 and 2022, the German guidelines were revised or developed on topics such as the management of anticoagulation during dermatological procedures, chronic pruritus, contact dermatitis, laser therapy of the skin, psoriasis vulgaris, rosacea, extracorporeal photopheresis, onychomycosis, mucous membrane pemphigoid and prevention of skin cancer. A selection of the most important recommendations and innovations in the guidelines is summarized here.
Topics: Humans; Dermatology; Germany; Psoriasis; Skin; Skin Neoplasms
PubMed: 37266595
DOI: 10.1007/s00105-023-05154-1 -
Transplantation and Cellular Therapy Dec 2023Extracorporeal photopheresis (ECP) has shown efficacy in treating graft-versus-host disease (GVHD). We aim to summarize eight years of real-world experience with...
Extracorporeal photopheresis (ECP) has shown efficacy in treating graft-versus-host disease (GVHD). We aim to summarize eight years of real-world experience with off-line ECP in our institution, in order to validate this treatment schedule and analyze predictive factors. All consecutive adult patients with steroid-dependent or steroid-refractory GVHD undergoing off-line ECP were included in this single-center retrospective study. ECP was performed with a Spectra Optia device, processing 1 total blood volume, at a twice-weekly frequency for acute GVHD (aGVHD) and once weekly for chronic GVHD (cGVHD), and tapered individually according to clinical response. The cumulative incidence of response, including complete response (CR) and partial response (PR), were compared among patients grouped by different baseline, apheresis, and disease characteristics. Between January 2015 and May 2022, a total of 1382 ECP procedures were proposed for 82 patients. No incidents were reported in 97% of the ECP sessions. GVHD responded in 78% of patients (aGVHD: 57% CR and 4% PR; cGVHD, 39% CR and 48% PR). Overall survival was statistically greater for aGVHD patients who responded to ECP compared to those who did not respond (67.5% versus 26% at 1 year; P = 0.037). Severity was an independent predictor of response in aGVHD, whereas the absence of mouth involvement and lower lymphocyte counts in the apheresis product correlated with a higher response in cGVHD. Our findings support the effectiveness of this treatment schedule for GVHD. Further investigation is required to identify ECP-specific predictive factors, given that findings are not homogeneous across studies.
Topics: Humans; Adult; Photopheresis; Retrospective Studies; Graft vs Host Disease; Steroids; Remission Induction
PubMed: 37703997
DOI: 10.1016/j.jtct.2023.09.001 -
Expert Review of Clinical Immunology Feb 2024Patients with chronic graft versus host disease (cGVHD) have low circulating regulatory T cells (Tregs). Interleukin-2(IL-2) is a growth factor for Tregs, and clinical... (Review)
Review
INTRODUCTION
Patients with chronic graft versus host disease (cGVHD) have low circulating regulatory T cells (Tregs). Interleukin-2(IL-2) is a growth factor for Tregs, and clinical trials have explored its use in cGVHD patients.
AREAS COVERED
Here we will discuss the biology of IL-2, its rationale for use and results of clinical trials in cGVHD. We also describe its mechanisms of action and alteration in gene expression in T-cell subsets after treatment with low dose IL-2 and photopheresis.
EXPERT OPINION
Clinical trials using Low dose IL-2 have been done at single centers in small patient series. The majority of the clinical responses seen with IL-2 in cGVHD are classified as partial responses and efficacy as a single agent is limited. Compared to currently approved oral therapies, it has to be administered subcutaneously and requires specialized processing for compounding and storage limiting its widespread use. Its use is associated with constitutional symptoms and local injection site reactions. Local reactions can be easily managed by supportive care practices like rotation of injection sites and premeditations, constitutional symptoms resolve with, dose reduction (25-50%) allowing for continued therapy. Additional studies are needed to define optimal combination strategies with approved agents. Longer acting formulations of IL-2 that require less frequent dosing may also improve patient compliance.
Topics: Humans; Interleukin-2; Bronchiolitis Obliterans Syndrome; Graft vs Host Disease; T-Lymphocytes, Regulatory; Immunotherapy; Chronic Disease
PubMed: 37921226
DOI: 10.1080/1744666X.2023.2279188 -
American Journal of Transplantation :... Mar 2024Prevention and management of allograft rejection urgently require more effective therapeutic solutions. Current immunosuppressive therapies used in solid organ... (Review)
Review
Prevention and management of allograft rejection urgently require more effective therapeutic solutions. Current immunosuppressive therapies used in solid organ transplantation, while effective in reducing the risk of acute rejection, are associated with substantial adverse effects. There is, therefore, a need for agents that can provide immunomodulation, supporting graft tolerance, while minimizing the need for immunosuppression. Extracorporeal photopheresis (ECP) is an immunomodulatory therapy currently recommended in international guidelines as an adjunctive treatment for the prevention and management of organ rejection in heart and lung transplantations. This article reviews clinical experience and ongoing research with ECP for organ rejection in heart and lung transplantations, as well as emerging findings in kidney and liver transplantation. ECP, due to its immunomodulatory and immunosuppressive-sparing effects, offers a potential therapeutic option in these settings, particularly in high-risk patients with comorbidities, infectious complications, or malignancies.
PubMed: 38490642
DOI: 10.1016/j.ajt.2024.03.012