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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 British Journal of Dermatology Oct 2023Extracorporeal photopheresis (ECP) has emerged as a systemic first-line immunomodulatory therapy in leukaemic cutaneous T-cell lymphoma (L-CTCL) and is now beginning to...
BACKGROUND
Extracorporeal photopheresis (ECP) has emerged as a systemic first-line immunomodulatory therapy in leukaemic cutaneous T-cell lymphoma (L-CTCL) and is now beginning to be utilized in other T-cell-mediated diseases. Although ECP has been used for nearly 30 years, its mechanisms of action are not sufficiently understood, and biomarkers for response are scarce.
OBJECTIVES
We aimed to investigate the immunomodulatory effects of ECP on cytokine secretion patterns in patients with L-CTCL, to help elucidate its mechanism of action.
METHODS
A total of 25 patients with L-CTCL and 15 healthy donors (HDs) were enrolled in this retrospective cohort study. Concentrations of 22 cytokines were simultaneously quantified by using multiplex bead-based immunoassays. Neoplastic cells in patients' blood were evaluated by flow cytometry.
RESULTS
Firstly, we observed a distinct cytokine profile pattern difference between L-CTCLs and HDs. There was a significant loss of tumour necrosis factor (TNF)-α, and significant increase of interleukins (IL)-9, IL-12 and IL-13 in the sera of patients with L-CTCL compared with HDs. Secondly, patients with L-CTCL who received ECP were classified as treatment responders and nonresponders according to the quantitative reduction of malignant burden in their blood. We evaluated cytokine levels in culture supernatants from patients' peripheral blood mononuclear cells (PBMCs) at baseline and 27 weeks after ECP initiation. Strikingly, PBMCs purified from ECP responders released statistically higher concentrations of innate immune cytokines IL-1α, IL-1β, granulocyte-macrophage colony-stimulating factor (GM-CSF) and TNF-α in comparison with ECP nonresponders. In parallel, responders showed clearance of erythema, reduction of malignant clonal T cells in the blood, and a potent boost of relevant innate immune cytokines in individual patients with L-CTCL.
CONCLUSIONS
Taken together, our results demonstrate that ECP stimulates the innate immune network, and facilitates redirection of the tumour-biased immunosuppressive microenvironment towards proactive antitumour immune responses. The alterations of IL-1α, IL-1β, GM-CSF and TNF-α can be used as biomarkers of response to ECP in patients with L-CTCL.
Topics: Humans; Cytokines; Photopheresis; Granulocyte-Macrophage Colony-Stimulating Factor; Tumor Necrosis Factor-alpha; Retrospective Studies; Leukocytes, Mononuclear; Lymphoma, T-Cell, Cutaneous; Immunity, Innate; Skin Neoplasms; Biomarkers; Tumor Microenvironment
PubMed: 37409661
DOI: 10.1093/bjd/ljad220 -
Vox Sanguinis Sep 2023Extracorporeal photopheresis (ECP) is a widespread cellular therapy for graft-versus-host disease, autoimmune diseases and Sézary disease. One of the main effects of...
BACKGROUND AND OBJECTIVES
Extracorporeal photopheresis (ECP) is a widespread cellular therapy for graft-versus-host disease, autoimmune diseases and Sézary disease. One of the main effects of ECP is the apoptosis of leukocytes, but the therapeutic mechanisms are not completely known. The aim of this study was to investigate the effects on red blood cells, platelets and the induction of reactive oxygen species.
MATERIALS AND METHODS
We used human cells from healthy blood donors to simulate in vitro the composition in an apheresis bag. Cells were treated with 8-methoxypsoralen (8-MOP) and UVA. Red blood cell stability, platelet activity and induction of reactive oxygen species were analysed.
RESULTS
After 8-MOP and UVA treatment, the red blood cells showed high cell integrity with low levels of eryptosis and no increase of free haemoglobin or red blood cell distribution width (RDW). Red blood cell immune-associated antigens CD59 and CD147 were hardly affected by the treatment. Platelet glycoproteins CD41, CD62P and CD63 indicated strong platelet activation after 8-MOP and UVA treatment. Reactive oxygen species were slightly but not significantly induced by the treatment.
CONCLUSION
The effect of the ECP therapy is probably not exclusively mediated by leukocytes. Platelet activation is another striking effect caused by the treatment of the apheresis product with 8-MOP/UVA. However, since we could hardly identify any evidence for eryptosis or haemolysis, it is unlikely that red blood cell eryptosis is part of the therapeutic mechanism. Further research on this topic seems to be promising.
Topics: Humans; Methoxsalen; Reactive Oxygen Species; Photopheresis; Blood Platelets; Erythrocytes
PubMed: 37401421
DOI: 10.1111/vox.13489 -
Journal of Clinical Apheresis Oct 2023A common required duty of pathology resident physicians while rotating on transfusion medicine is the medical oversight of the therapeutic apheresis service. A task...
BACKGROUND
A common required duty of pathology resident physicians while rotating on transfusion medicine is the medical oversight of the therapeutic apheresis service. A task often performed on this clinical medicine service is formulating and writing orders for therapeutic apheresis procedures. The EpicCare tool called the therapy plan provides unique advantages over a standard electronic order set for therapeutic apheresis.
MATERIALS AND METHODS
Transfusion medicine physicians, apheresis nurses, pharmacists, and information technology professionals collaborated to create therapy plans for three therapeutic apheresis procedures: plasmapheresis, red cell exchange, and photopheresis.
RESULTS
Therapy plans were implemented and have been well-received for several years. Over a six-year time period, a total of 613 therapy plans were created and signed. We speculate that this implementation may have increased both physician efficiency and patient safety.
CONCLUSION
This article reports our experience using therapy plans in EpicCare in order to raise awareness of this tool and to serve as an encouragement for wider adoption.
Topics: Humans; Blood Component Removal; Plasmapheresis; Photopheresis; Clinical Medicine; Patient Safety
PubMed: 37376707
DOI: 10.1002/jca.22072 -
Best Practice & Research. Clinical... Jun 2023Apheresis is an automated process to separate the whole blood of a patient or a donor, collect or remove specific blood components, and return the remaining back to the... (Review)
Review
Apheresis is an automated process to separate the whole blood of a patient or a donor, collect or remove specific blood components, and return the remaining back to the individual. Apheresis is an integral part of blood and marrow transplantation and has been increasingly utilized in novel cellular therapies for a variety of blood disorders. This review uses clinical cases to highlight the multiple roles of apheresis in the care of adult leukaemia patients, including therapeutic leukapheresis in hyperleukocytosis, mobilized peripheral blood hematopoietic progenitor cell collection in donors, mononucleated cell collection in preparation of donor lymphocyte infusion or chimeric antigen receptor T cells manufacture, and extracorporeal photopheresis in the treatment of graft versus host diseases.
Topics: Humans; Adult; Blood Component Removal; Leukapheresis; Photopheresis; Immunotherapy, Adoptive; Leukemia; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation
PubMed: 37353291
DOI: 10.1016/j.beha.2023.101467 -
Cureus May 2023Steam, dry heat, radiation, ethylene oxide gas, evaporated hydrogen peroxide, and many other sterilization methods are used to sanitize medical equipment...
Steam, dry heat, radiation, ethylene oxide gas, evaporated hydrogen peroxide, and many other sterilization methods are used to sanitize medical equipment (e.g., chlorine dioxide gas, nitrogen dioxide, and vaporized peracetic acid). The benefits of ethylene oxide (EO) are its great processing capabilities, high ionic conductivity, high flexibility, low cost, and exceptional adhesive qualities. Patients on hemodialysis, those undergoing extracorporeal photopheresis, and plasmapheresis donors have all reported allergic reactions to EO. Differentiating between IgE-mediated anaphylaxis and anaphylactoid reactions is often impossible in practice due to the wide range of clinical symptoms. The infrequency of EO reactions coupled with healthcare personnel's lack of familiarity with this clinical phenomenon may result in their underdiagnosis. We describe the case of a platelet donor who developed an allergy, while donating at a transfusion facility, due to an ethylene oxide-sterilized apheretic kit. We aim to draw attention to the fact that care should be given while handling cases of this nature as they can become life-threatening.
PubMed: 37332446
DOI: 10.7759/cureus.39126 -
Cureus May 2023The aim of the study was to systematically analyze the influence of extracorporeal photopheresis (ECP) on the quality of life (LQ) and the course of the disease in...
Effects of Extracorporeal Photopheresis on Quality of Life and the Course of Diseases in Patients With Mycosis Fungoides and Graft-Versus-Host Disease: A Single-Center Analysis.
INTRODUCTION
The aim of the study was to systematically analyze the influence of extracorporeal photopheresis (ECP) on the quality of life (LQ) and the course of the disease in patients with Mycosis Fungoides (MF), as well as with Graft-versus-Host Disease (GvHD).
METHODS
LQ was monitored retrospectively by using the dermatology life quality index (DLQI) and Skindex-29 test before ECP onset and after the last ECP. Disease parameters were assessed by objective criteria i.e. number of associated medical drugs taken, intervals between therapeutic cycles, gradual change of the disease, and eventual side-effects and complications of ECP therapy.
RESULTS
Fifty-one patients were treated with ECP during 2008-19; 19 out of 51 died, and follow-up was not completed in 13 patients. Finally, treatment protocols of 671 ECP procedures were evaluated in 19 patients (10 MF; 9 GvHD). MF and GvHD subpopulations did not differ in the individual scores of LQ questions, either before the outset or after the last ECP. DLQI and Skindex-29 scores were ameliorated by the ECP therapy (p= 0.001 and p< 0.001, respectively) due to improvement of individual scores of feelings, daily/social activities (p< 0.05), and functionality (p≤ 0.05). The median interval between ECP cycles was extended from two to eight weeks (p= 0.001). Needs of GvHD patients for drugs being received for the underlying disease were reduced (p= 0.035). Two of the 10 MF patients worsened from stage IIA to IIIA. Severe or minor side effects leading to a therapy interruption were not recorded.
CONCLUSION
Patients with GvHD experienced a notable decrease in the administration of drugs for their underlying condition, and there were no instances of severe side effects that resulted in the discontinuation of treatment. ECP is safe and effective for the treatment of MF and GvHD.
PubMed: 37309341
DOI: 10.7759/cureus.38929 -
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 -
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 -
American Journal of Clinical Pathology Oct 2023The US health care payment system is complex and difficult to interpret. Although federal regulations require that more data, in the form of charges and negotiated...
OBJECTIVES
The US health care payment system is complex and difficult to interpret. Although federal regulations require that more data, in the form of charges and negotiated rates, be made available, compliance remains variable. We review chargemaster and negotiated rate values for extracorporeal photopheresis (ECP) to assess this variability. We sought to determine the availability of chargemaster and negotiated rates for health care consumers and to assess compliance and pricing among institutions using ECP as a model for apheresis billing.
METHODS
We obtained ECP chargemaster data and negotiated rates from 20 institutions. We analyzed the availability of ECP chargemaster data and compared values with a previously published historic cohort. We evaluated the availability of negotiated rates and determined relative reimbursement using charge to reimbursement ratios. We determined calculated fines for hospitals based on bed size.
RESULTS
Chargemaster availability increased from 2019 to 2022, though only 65% (13/20) of hospitals had both chargemaster and negotiated rate data. Chargemaster prices increased significantly from 2019 to 2022 (range, $3,586.83-$34,043.00). We reviewed 1,191 negotiated rates, with institutions averaging 93.6 different rates (SD, 189.5). Negotiated rates were variable, ranging from $3,586.83 to $34,043.00 per procedure. Reimbursement was higher among private insurers compared with reported Centers for Medicare & Medicaid Services negotiated rates. Of the 35% (7/20) that lacked chargemaster and negotiated rates, institutions faced an average annual fine of $1,430,800.
CONCLUSIONS
Despite recent financial penalties, ECP pricing data are often unavailable or inadequate. Current available resources are unlikely to benefit the average health care consumer who requires ECP.
Topics: Aged; Humans; Blood Component Removal; Hospitals; Medicare; Outpatients; Photopheresis; United States
PubMed: 37265164
DOI: 10.1093/ajcp/aqad059