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Journal of Clinical and Experimental... Feb 2015Graft versus host disease (GVHD) is one of the most frequent and serious complications of hematopoietic stem cell transplantation, and is regarded as the leading cause... (Review)
Review
Graft versus host disease (GVHD) is one of the most frequent and serious complications of hematopoietic stem cell transplantation, and is regarded as the leading cause of late mortality unrelated to the underlying malignant disease. GVHD is an autoimmune and alloimmune disorder that usually affects multiple organs and tissues, and exhibits a variable clinical course. It can manifest in either acute or chronic form. The acute presentation of GVHD is potentially fatal and typically affects the skin, gastrointestinal tract and liver. The chronic form is characterized by the involvement of a number of organs, including the oral cavity. Indeed, the oral cavity may be the only affected location in chronic GVHD. The clinical manifestations of chronic oral GVHD comprise lichenoid lesions, hyperkeratotic plaques and limited oral aperture secondary to sclerosis. The oral condition is usually mild, though moderate to severe erosive and ulcerated lesions may also be seen. The diagnosis is established from the clinical characteristics, though confirmation through biopsy study is sometimes needed. Local corticosteroids are the treatment of choice, offering overall response rates of close to 50%. Extracorporeal photopheresis and systemic corticosteroids in turn constitute second line treatment. Oral chronic GVHD is not considered a determinant factor for patient survival, which is close to 52% five years after diagnosis of the condition. Key words:Chronic graft-versus-host disease, oral chronic graft-versus-host disease, pathogenics, management, survival.
PubMed: 25810826
DOI: 10.4317/jced.51975 -
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 -
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 -
HemaSphere Jun 2021Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a potentially curative therapy for patients suffering from hematological malignancies, and its... (Review)
Review
Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a potentially curative therapy for patients suffering from hematological malignancies, and its therapeutic success is based on the graft-versus-leukemia (GvL) effect. Severe acute and chronic graft-versus-host disease (GvHD) are life-threatening complications after allo-HCT. To date, most of the approved treatment strategies for GvHD rely on broadly immunosuppressive regimens, which limit the beneficial GvL effect by reducing the cytotoxicity of anti-leukemia donor T-cells. Therefore, novel therapeutic strategies that rely on immunomodulatory rather than only immunosuppressive effects could help to improve patient outcomes. Treatments should suppress severe GvHD while preserving anti-leukemia immunity. New treatment strategies include the blockade of T-cell activation via inhibition of dipeptidyl peptidase 4 and cluster of differentiation 28-mediated co-stimulation, reduction of proinflammatory interleukin (IL)-2, IL-6 and tumor necrosis factor-α signaling, as well as kinase inhibition. Janus kinase (JAK)1/2 inhibition acts directly on T-cells, but also renders antigen presenting cells more tolerogenic and blocks dendritic cell-mediated T-cell activation and proliferation. Extracorporeal photopheresis, hypomethylating agent application, and low-dose IL-2 are powerful approaches to render the immune response more tolerogenic by regulatory T-cell induction. The transfer of immunomodulatory and immunosuppressive cell populations, including mesenchymal stromal cells and regulatory T-cells, showed promising results in GvHD treatment. Novel experimental procedures are based on metabolic reprogramming of donor T-cells by reducing glycolysis, which is crucial for cytotoxic T-cell proliferation and activity.
PubMed: 34095764
DOI: 10.1097/HS9.0000000000000581 -
Frontiers in Bioscience (Landmark... Jan 2009Extracorporeal photoimmunotherapy-photopheresis (ECP) is an immunomodulatory therapy, which basically consists of separating the patient's leucocyte rich plasma from the... (Review)
Review
Extracorporeal photoimmunotherapy-photopheresis (ECP) is an immunomodulatory therapy, which basically consists of separating the patient's leucocyte rich plasma from the red blood cell fraction, followed by extracorporeal administration of a photosensitizer and UVA light prior to reinfusion of the treated cells. Successful use of ECP has been reported in patients with cutaneous T cell lymphoma, the Sezary syndrome variant, graft-versus-host disease, cardiac transplant rejection and other T cell mediated/autoimmune and autoimmune diseases. Apoptosis of malignant lymphocytes and presentation of their antigens to anti-tumor CD8+ T cells with induction of an anticlonotypic response by CD8+ effector cells against the CD4+ neoplastic T cells was one of the intial mechanisms of action proposed. The exact mechanism by which ECP exerts its therapeutic effect remains to be further explored and is still uncertain. The better understanding of its mode of action and the clinical benefits of ECP are important findings that provide additional tools to increase the therapeutic armamentarium in a number of acute and chronic T cell mediated diseases.
Topics: Graft Rejection; Graft vs Host Disease; Humans; Immunotherapy; Lymphoma, T-Cell; Photopheresis; Scleroderma, Systemic; Skin Neoplasms
PubMed: 19273388
DOI: 10.2741/3566 -
Acta Dermato-venereologica Mar 2018Scleroedema adultorum Buschke is a rare skin disease, which can be divided into 3 subtypes: classic type, occurring after respiratory infections; a type lacking... (Review)
Review
Scleroedema adultorum Buschke is a rare skin disease, which can be divided into 3 subtypes: classic type, occurring after respiratory infections; a type lacking association with infections; and a type associated with diabetes. Scleroedema adultorum Buschke is characterized by thickening and tightening of the skin, which typically starts at the neck. In half of patients, spontaneous remission may occur. The aim of this systematic review is to summarize all reported treatments for scleroedema adultorum Buschke, based on articles from PubMed database, using the query "scleroedema adultorum Buschke treatment", English and German, published between 1970 and 2016 and documenting adequate treatments. The results are based mainly on individual case reports, small case series, and retrospective studies often reporting unsuccessful results. Treatment options include topical as well as systemic treatments, and physical modalities. There is a need for randomized controlled trials and studies on long-term outcomes after treatment.
Topics: Dermatologic Agents; Humans; Immunosuppressive Agents; PUVA Therapy; Photopheresis; Remission, Spontaneous; Risk Factors; Scleredema Adultorum; Skin; Treatment Outcome
PubMed: 29136263
DOI: 10.2340/00015555-2846 -
Transplantation and Cellular Therapy Jun 2023Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the sole curative option for many patients diagnosed with hematologic malignancies. A major obstacle is... (Randomized Controlled Trial)
Randomized Controlled Trial
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the sole curative option for many patients diagnosed with hematologic malignancies. A major obstacle is graft-versus-host disease (GVHD), causing significant morbidity and mortality. Extracorporeal photopheresis (ECP) is an increasingly applied treatment for GVHD, owing in part to its favorable safety profile. In contrast, reports on the use of ECP to prevent GVHD are rare, and randomized controlled trials (RCTs) are lacking. We conducted an RCT to assess whether ECP applied post-transplantation could prevent the development of GVHD within the first year of transplantation. We enrolled 157 patients (age 18 to 74 years) with a hematologic malignancy undergoing their first allo-HSCT, randomized as 76 to the intervention group and 81 to the control group. ECP was initiated directly on engraftment and was planned twice weekly for 2 weeks, then once weekly for 4 weeks. GVHD, relapse, and death were analyzed by Cox regression analysis. During the first year, 45 patients in the intervention group and 52 control patients developed GVHD (hazard ratio [HR], .82; 95% confidence interval [CI], .55 to 1.22; P = .32). There were no differences in acute or chronic GVHD or its organ distribution in this intention-to-treat RCT. A per-protocol analysis revealed a significant difference in GVHD between the intervention group (per-protocol; n = 39 of 76) and the control group (n = 77), 46% versus 68%, respectively (HR, .47; 95% CI, .27 to .80; P = .006). Relapse occurred in 15 patients in the intervention group and in 11 control patients (HR, 1.38; 95% CI, .64 to 3.01; P = .42). GVHD-free relapse-free survival, event-free survival, overall survival, and nonrelapse mortality did not differ significantly between the 2 study groups. There also was no significant difference in immune reconstitution between the 2 groups. This first intention-to-treat RCT investigating ECP as GVHD prophylaxis in allo-HSCT for hematologic malignancy does not support the use of ECP as an adjunct to standard drug-based GVHD prophylaxis.
Topics: Adolescent; Adult; Aged; Humans; Middle Aged; Young Adult; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Neoplasm Recurrence, Local; Photopheresis
PubMed: 36878428
DOI: 10.1016/j.jtct.2023.02.023 -
Journal of Thoracic Disease Nov 2021Outcomes after lung transplantation are limited by chronic lung allograft dysfunction (CLAD). The incidence of CLAD is high, and its clinical course tends to be... (Review)
Review
Outcomes after lung transplantation are limited by chronic lung allograft dysfunction (CLAD). The incidence of CLAD is high, and its clinical course tends to be progressive over time, culminating in graft failure and death. Indeed, CLAD is the leading cause of death beyond the first year after lung transplantation. Therapy for CLAD has been limited by a lack of high-quality studies to guide management. In this review, we will discuss the diagnosis of CLAD in light of the recent changes to definitions and will discuss the current clinical evidence available for treatment. Recently, the diagnosis of CLAD has been subdivided into bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). The current evidence for treatment of CLAD mainly revolves around treatment of BOS with more limited data existing for RAS. The best supported treatment to date for CLAD is the macrolide antibiotic azithromycin which has been associated with a small improvement in lung function in a minority of patients. Other therapies that have more limited data include switching immunosuppression from cyclosporine to tacrolimus, fundoplication for gastroesophageal reflux, montelukast, extracorporeal photopheresis (ECP), aerosolized cyclosporine, cytolytic anti-lymphocyte therapies, total lymphoid irradiation (TLI) and the antifibrotic agent pirfenidone. Most of these treatments are supported by case series and observational studies. Finally, we will discuss the role of retransplantation for CLAD.
PubMed: 34992842
DOI: 10.21037/jtd-2021-19 -
World Journal of Transplantation Oct 2019Therapeutic apheresis is a cornerstone of therapy for several conditions in transplantation medicine and is available in different technical variants. In the setting of... (Review)
Review
Therapeutic apheresis is a cornerstone of therapy for several conditions in transplantation medicine and is available in different technical variants. In the setting of kidney transplantation, immunological barriers such as ABO blood group incompatibility and preformed donor-specific antibodies can complicate the outcome of deceased- or living- donor transplantation. Postoperatively, additional problems such as antibody-mediated rejection and a recurrence of primary focal segmental glomerulosclerosis can limit therapeutic success and decrease graft survival. Therapeutic apheresis techniques find application in these issues by separating and selectively removing exchanging or modifying pathogenic material from the patient by an extracorporeal aphaeresis system. The purpose of this review is to describe the available techniques of therapeutic aphaeresis with their specific advantages and disadvantages and examine the evidence supporting the application of therapeutic aphaeresis as an adjunctive therapeutic option to immunosuppressive agents in protocols before and after kidney transplantation.
PubMed: 31750088
DOI: 10.5500/wjt.v9.i6.103 -
Clinical Reviews in Allergy & Immunology Apr 2021Ultraviolet blood irradiation (UBI) was used with success in the 1930s and 1940s for a variety of diseases. Despite the success, the lack of understanding of the... (Review)
Review
Ultraviolet blood irradiation (UBI) was used with success in the 1930s and 1940s for a variety of diseases. Despite the success, the lack of understanding of the detailed mechanisms of actions, and the achievements of antibiotics, phased off the use of UBI from the 1950s. The emergence of novel viral infections, from HIV/AIDS to Ebola, from SARS and MERS, and SARS-CoV-2, bring back the attention to this therapeutical opportunity. UBI has a complex virucidal activity, mostly acting on the immune system response. It has effects on lymphocytes (T-cells and B-cells), macrophages, monocytes, dendritic cells, low-density lipoprotein (LDL), and lipids. The Knott technique was applied for bacterial infections such as tuberculosis to viral infections such as hepatitis or influenza. The more complex extracorporeal photopheresis (ECP) is also being applied to hematological cancers such as T-cell lymphomas. Further studies of UBI may help to create a useful device that may find applications for novel viruses that are resistant to known antivirals or vaccines, or also bacteria that are resistant to known antibiotics.
Topics: Bacteria; Bacterial Infections; COVID-19; Cytokines; Dendritic Cells; Humans; Lymphocytes; Macrophages; Monocytes; Photopheresis; SARS-CoV-2; Signal Transduction; Treatment Outcome; Ultraviolet Rays
PubMed: 33026601
DOI: 10.1007/s12016-020-08811-8