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Frontiers in Immunology 2020As the use of hematopoietic stem cell transplantation (HSCT) has become a more widespread and effective treatment for hematological malignant and non-malignant... (Review)
Review
As the use of hematopoietic stem cell transplantation (HSCT) has become a more widespread and effective treatment for hematological malignant and non-malignant conditions, the need to minimize the harmful effects of graft- vs.-host disease (GvHD) has become more important in achieving good outcomes. With diagnosis of GvHD reliant on its clinical manifestations, research into biomarkers for the diagnosis, progression, and even for the prediction of disease, is imperative to combating the high levels of morbidity and mortality post-HSCT. Despite the development of novel treatment approaches to GvHD, corticosteroids remain the standard first-line treatment, with immunosuppressant therapies as second-line options. These strategies however have significant limitations and associated complications. Extracorporeal Photopheresis (ECP) has shown to be effective and safe in treating patients with symptomatic GvHD. ECP has been shown to have varied effects on multiple parts of the immune system and does not appear to increase the risk of relapse or infection in the post HSCT setting. Even so, ECP can be logistically more complex to organize and requires patients to be sufficiently stable. This review aims to summarize the potential role of biomarkers to help guide individualized treatment decisions in patients with acute and chronic GvHD. In relation to ECP, robust biomarkers of GvHD will be highly useful in informing patient selection, intensity and duration of the ECP schedule, monitoring of response and other treatment decisions alongside the concurrent administration of other GvHD therapies. Further research is warranted to establish how GvHD biomarkers are best incorporated into ECP treatment pathways with the goal of tailoring ECP to the needs of individual patients and maximizing benefit.
Topics: Animals; Biomarkers; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Photopheresis
PubMed: 32082329
DOI: 10.3389/fimmu.2020.00081 -
Transfusion and Apheresis Science :... Apr 2015The immune system is tasked with the unique challenge of recognizing foreign pathogens and damaged cells while at the same time preserving and protecting the integrity... (Review)
Review
The immune system is tasked with the unique challenge of recognizing foreign pathogens and damaged cells while at the same time preserving and protecting the integrity of "self". When this process fails, severe consequences including cancer and autoimmunity are the end result. Current therapies aimed at treating autoimmune disorders result in generalized immunosuppression and place the patient at increased risk for infection and malignancy. ECP is a potential therapeutic intervention that recapitulates natural physiologic processes of tolerance induction to restore immune homeostasis. Several clinical trials suggest that ECP may be used to treat a broad spectrum of autoimmune diseases.
Topics: Animals; Apoptosis; Arthritis, Rheumatoid; Autoimmune Diseases; Clinical Trials as Topic; Crohn Disease; Diabetes Mellitus, Type 1; Eosinophilia; Epidermolysis Bullosa Acquisita; Fasciitis; Homeostasis; Humans; Immune Tolerance; Immunosuppression Therapy; Immunosuppressive Agents; Lichen Planus; Lupus Erythematosus, Systemic; Multiple Sclerosis; Pemphigus; Photopheresis; Psoriasis; Scleroderma, Systemic; Scleromyxedema; Spondylitis, Ankylosing; T-Lymphocytes, Regulatory
PubMed: 25886694
DOI: 10.1016/j.transci.2015.02.005 -
Transfusion Medicine and Hemotherapy :... Jun 2020Extracorporeal photopheresis (ECP) is a cell-based immunotherapy that involves the reinfusion of autologous leukocytes after exposure to psoralen and UVA. The treatment... (Review)
Review
Extracorporeal photopheresis (ECP) is a cell-based immunotherapy that involves the reinfusion of autologous leukocytes after exposure to psoralen and UVA. The treatment has been used for over 30 years, at first on patients with cutaneous T-cell lymphoma (CTCL) and later for the management of patients with graft-versus-host disease (GvHD), sclerosing disorders, atopic dermatitis, and other diseases that may share the common driving factor of a pathogenic T-cell clone or clones in blood circulation. Patients with clinical improvement mount an antigen-specific immune response that may have tolerance traits in the case of GvHD or anticlonal cytotoxic characteristics in the case of CTCL. The exact mechanisms that dictate one response or the other are not fully understood, but the evidence accumulated so far indicates that multiple events occur simultaneously and consequentially contribute to the end result. These include contact of cells with the outside (plastics and tubing of the ECP apparatus), exposure to psoralen and UVA that activates platelets, monocytes, and other myeloid cells, the release of damage-associated molecular patterns, differentiation of monocytes into dendritic cells, and generation and successive presentation of numerous antigens after the phagocytosis of apoptotic cells. Once reintroduced, the ECP product increases the frequency and activity of regulatory T cells (Tregs), shifts the systemic cytokine balance, and promotes extravasation of immune cells that together shape the effects of this treatment. In this review, we summarize the seminal work and most recent literature of the therapeutic mechanisms and reflect on future avenues of improvements and applications of ECP.
PubMed: 32595427
DOI: 10.1159/000508479 -
Therapeutic Apheresis and Dialysis :... Apr 2015From the 1980s, extracorporeal photochemotherapy (ECP) has been shown to be effective in a variety of pathological conditions such as erythrodermic cutaneous T-cell... (Review)
Review
From the 1980s, extracorporeal photochemotherapy (ECP) has been shown to be effective in a variety of pathological conditions such as erythrodermic cutaneous T-cell lymphoma, autoimmune diseases, solid organ allograft rejection and graft versus host disease. To date, ECP represents a non-aggressive immune modulatory therapy with a low spectrum of toxicity. ECP reduces the alloreactivity promoting the immune tolerance to self. At the same time, it allows the maintenance of immune response integrity of both naive and memory T-cells. However, the molecular mechanisms of action by which ECP exerts its therapeutic activity are still under investigation. Here, we review molecular mechanisms and clinical applications involved in ECP. The outcome of ECP is difficult due to the lack of reliable predictor factors for the selection of patients and their adequate follow-up. Since the study of such predictors is important, we also describe some biological markers that enable us to investigate the clinical management of the patients considered for the use of ECP.
Topics: Autoimmune Diseases; Graft vs Host Disease; Humans; Lymphoma, T-Cell, Cutaneous; Photopheresis
PubMed: 25363837
DOI: 10.1111/1744-9987.12245 -
Transfusion and Apheresis Science :... Jun 2023Extracorporeal photopheresis (ECP) is a cell therapy originally employed for cutaneous T cell lymphoma and later for GvHD, solid organ rejection and other immunological... (Review)
Review
Extracorporeal photopheresis (ECP) is a cell therapy originally employed for cutaneous T cell lymphoma and later for GvHD, solid organ rejection and other immunological diseases demonstrating an excellent safety profile. Mononuclear cell (MNCs) apoptosis triggered by UV-A light irradiation in the presence of 8-methoxypsoralene has a key role in priming the cells, ultimately leading to immunomodulation. We report preliminary data about an evaluation of the new automated irradiator device LUMILIGHT (Pelham Crescent srl) for off-line ECP. Fifteen MNCs samples collected by apheresis from 15 adult patients undergoing ECP at our Center were cultured immediately after irradiation along with untreated samples and evaluated at 24, 48 and 72 h timepoints for T cell apoptosis and viability by flow cytometry with Annexin V and Propide Iodidum staining. Post irradiation Hematocrit (HCT), calculated by the device, was compared with that of the automated cell counter. Bacterial contamination was also tested. In irradiated samples after 24-48 and 72 h, the average total apoptosis was 47 %, 70 % and 82 %, respectively, showing a significant difference from untreated samples; residual viable lymphocytes at 72 h were, on average, 18 %. The greatest initiation of apoptosis occurred from 48 h of irradiation onwards. Average early apoptosis of irradiated samples decreased over time (26 %, 17 % and 10 % at 24, 48 and 72 h, respectively). HCT measured by LUMILIGHT was over-estimated, possibly due to the low pre irradiation red blood cell contamination. Bacterial tests resulted negative. Our study showed the LUMILIGHT device to be a valid instrument for MNCs irradiation with good handling and no major technical problems as well as no adverse events in the patients. Our data need to be confirmed in larger studies.
Topics: Adult; Humans; Photopheresis; Blood Component Removal; Lymphocytes; Leukocytes; Skin Neoplasms; Graft vs Host Disease
PubMed: 37202323
DOI: 10.1016/j.transci.2023.103724 -
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 -
Transfusion Jun 2020Extracorporeal photopheresis (ECP) is an immunosuppressive treatment that involves leukocyte apheresis, psoralen and UV light treatment, and subsequent reinfusion....
BACKGROUND
Extracorporeal photopheresis (ECP) is an immunosuppressive treatment that involves leukocyte apheresis, psoralen and UV light treatment, and subsequent reinfusion. Patients treated with ECP are usually immunosuppressed. Bacterial contamination therefore poses a much unwanted risk, but incidence data are lacking.
PATIENTS AND METHODS
We screened all 1922 consecutive ECP procedures scheduled within a roughly 3-year period for eligibility. Those with missing data on ECP method (inline or offline) or type of venous access (peripheral or central) were excluded. ECPs with complete aerobic and anaerobic microbial testing of baseline patient blood samples (n = 1637) and of ECP cell concentrates (n = 1814) were included in the analysis.
RESULTS
A test for microbial contamination was positive for 1.82% of the cell concentrates, with central venous access was the most significant risk factor for the contamination (odds ratio = 19). Patient blood samples were positive in 3.85% of cases, but no patients became septic. Staphylococcus spp. were most abundant, and products with bacterial contamination did not cause side effects after reinfusion. There were no significant differences in contamination rates between inline and offline ECP.
CONCLUSION
These findings stress the importance of sterile procedures and the benefits of using peripheral over central venous access for reducing the risk of bacterial contamination in ECP.
Topics: Adolescent; Adult; Aged; Central Venous Catheters; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Photopheresis; Staphylococcal Infections; Staphylococcus
PubMed: 32315092
DOI: 10.1111/trf.15801 -
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 -
Transfusion and Apheresis Science :... Oct 2021The aim of the study was to investigate safety and if extracorporeal photopheresis (ECP) may change health criteria (HC) and quality of life (QoL).
UNLABELLED
The aim of the study was to investigate safety and if extracorporeal photopheresis (ECP) may change health criteria (HC) and quality of life (QoL).
MATERIAL AND METHOD
560 patients (33 % women) were treated with ECP for a total of 13,871 procedures during a 17-years period. Mean age was 48 years (±18, range 3-81 years). Self-estimation of QoL was graded: 0 (suicidal) up to 10 (best ever) and HC: 0 (Bed ridden, ICU condition) up to 10 (athletic). Adverse events were analyzed. ANOVA and paired comparisons were performed.
RESULTS
Patients were treated due to graft versus host disease (GVHD, n = 317), skin lymphoma (n = 70), solid organ transplants (n = 47), skin diseases (n = 20) and other diseases (n = 106). Adverse events (AEs) were registered in 5.4 % of the first treatments and in 1.2 % of the subsequent procedures. Severe AEs were present in 0.04 % of all procedures. No patient died due to the procedure. Tingling and stitching were the most common AE. For those with GVHD an improvement was noticed within approximately 10 procedures of ECP in the severity stage, QoL (from a mean of 6.1 to 6.8, p < 0.002) and the HC (6.1 -> 6.4, p < 0.014) and improved further with added procedures.
CONCLUSION
Photopheresis is an established therapy with few side effects. The present study of soft variables indicate that GVHD shows benefits upon ECP within approximately 10 procedures in regard to the severity of mainly skin GVHD, and lower baseline levels of HC and QoL.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Chronic Disease; Female; Graft vs Host Disease; Hemodynamics; Humans; Lymphoma; Male; Middle Aged; Photopheresis; Quality of Life; Registries; Retrospective Studies; Skin Neoplasms; Young Adult
PubMed: 34059472
DOI: 10.1016/j.transci.2021.103172 -
Journal of Clinical Apheresis Aug 2015Systemic autoimmune diseases (AID) have multiorgan, heterogeneous clinical presentations and are characterized by dysregulation of the immune system, immunodeficiency,... (Review)
Review
Systemic autoimmune diseases (AID) have multiorgan, heterogeneous clinical presentations and are characterized by dysregulation of the immune system, immunodeficiency, irreversible organ damage and increased morbidity and mortality. Preventing or decreasing flares of AID correlate with durable disease control, significant reduction of inflammation and prevention of disability or therapy-related toxicity. There is an urgent need for better treatment of severe, therapy-refractory AID. Extracorporeal photopheresis (ECP) is a cell-based immunomodulatory treatment which has been extensively used in variety of autoimmune disorders for the last two decades. ECP treatment is FDA approved for the treatment of cutaneous T-cell lymphoma (CTCL) with particularly promising results seen in graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HCT). Prolonged therapy is safe, well tolerated and allows reduction of systemic immunosuppression in therapy-refractory patients. Both clinical and experimental evidence suggest that ECP mechanism of action is characterized by apoptosis and phagocytosis of activated cells by antigen-presenting cells (APC), secretion of anti-inflammatory cytokines and stimulation of regulatory T cells (Tregs). The focus of this paper is to review the current evidence of ECP use in the treatment of AID. Here, we summarize the experience of nine major AID from 65 published reports. The key findings demonstrate substantial evidence of ECP feasibility, safety and in some AID also promising efficacy. However, the role of ECP in AID therapy is not established as most published studies are retrospective with limited number of patients and the trials are small or poorly standardized. The available data support future investigations of ECP as a therapeutic modality for the treatment of AID in well-designed prospective clinical studies. J
Topics: Apoptosis; Autoimmune Diseases; Blood Component Removal; Clinical Trials as Topic; Humans; Immune Tolerance; Immunosuppression Therapy; Immunosuppressive Agents; Inflammation; Methoxsalen; Phagocytosis; Photopheresis; Photosensitizing Agents; Research Design; Retrospective Studies; Ultraviolet Rays
PubMed: 25546289
DOI: 10.1002/jca.21367