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Hematology. American Society of... Dec 2017Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative option for many disease states. Despite significant improvements in strategies used... (Review)
Review
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative option for many disease states. Despite significant improvements in strategies used to prevent and treat acute and chronic graft-versus-host disease (a/cGVHD), they continue to negatively affect outcomes of HSCT significantly. Standard, first-line treatment consists of corticosteroids; beyond this, there is little consistency in therapeutic regimens. Current options include the addition of various immunosuppressive agents, the use of which puts patients at even higher risks for infection and other morbidities. Extracorporeal photopheresis (ECP) is a widely used cellular therapy currently approved by the US Food and Drug Administration for use in patients with cutaneous T-cell lymphoma; it involves the removal of peripherally circulating white blood cells, addition of a light sensitizer, exposure to UV light, and return of the cells to the patient. This results in a series of events ultimately culminating in transition from an inflammatory state to that of tolerance, without global immunosuppression or known long-term adverse effects. Large-scale, prospective studies of the use of ECP in patients with a/cGVHD are necessary in order to develop the optimal treatment regimens.
Topics: Acute Disease; Allografts; Chronic Disease; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, T-Cell, Cutaneous; Photopheresis
PubMed: 29222315
DOI: 10.1182/asheducation-2017.1.639 -
Current Problems in Dermatology 2012Graft-versus-host disease (GVHD) is the primary cause of non-relapse-related morbidity and mortality in patients who undergo hematopoietic stem cell transplantation.... (Review)
Review
Graft-versus-host disease (GVHD) is the primary cause of non-relapse-related morbidity and mortality in patients who undergo hematopoietic stem cell transplantation. Dermatologic manifestations are common in both acute and chronic GVHD. In the acute setting, skin involvement often provides the first indication of GVHD and may progress to erythroderma and even skin necrolysis. In the chronic phase, skin involvement is extraordinarily polymorphic, potentially involves all layers of the skin and subcutaneous tissue, and presents in sclerotic and nonsclerotic forms. Management of cutaneous disease is challenging and ideally employs a multi-disciplinary approach and an understanding of the multiple medical issues facing patients with GVHD. The dermatologist plays a key role in caring for the patient with GVHD by providing an accurate diagnosis, determination of disease activity and response to treatment, and appropriate consideration of all available treatment modalities, including topical, systemic, and physical interventions (e.g. phototherapy, extracorporeal photopheresis). This chapter describes the cutaneous manifestations of acute and chronic GVHD and provides an evidence-based review of current treatment interventions for patients with GVHD skin disease.
Topics: Acute Disease; Antineoplastic Agents; Chronic Disease; Evidence-Based Medicine; Graft vs Host Disease; Humans; Immunosuppressive Agents; Skin Diseases
PubMed: 22377924
DOI: 10.1159/000335270 -
The European Respiratory Journal Jan 2004In 2002, equal numbers of lung transplantation (LTx) were performed with or without induction therapy with antilymphocyte antibodies, monoclonal anti-CD3 antibody or... (Comparative Study)
Comparative Study Review
In 2002, equal numbers of lung transplantation (LTx) were performed with or without induction therapy with antilymphocyte antibodies, monoclonal anti-CD3 antibody or anti-interleukin-2-receptor monoclonal antibodies. It remains to be established if induction therapy after LTx is beneficial or deleterious for long-term graft and patient survival. The vast majority of lung transplant recipients receive a triple-drug maintenance regimen including a calcineurin inhibitor, a cell-cycle inhibitor and steroids. Equal proportions receive cyclosporin A (CsA) and tacrolimus (Tac). There is also a trend to prescribe mycophenolate mofetil (MMF) instead of azathioprine (Aza). Steroid withdrawal is uncommon even 5 yrs after transplantation. The superiority of Tac over CsA as a maintenance agent has not been established to date, and the administration of MMF instead of Aza in combination with CsA and steroids did not improve graft or patient survival in a recent international, prospective, randomised, controlled trial. Shift from cyclosporin A to tacrolimus has emerged as the first treatment step of refractory acute rejection followed by high-dose steroids or antilymphocyte agents, total lymphoid irradiation or photopheresis. The treatment of chronic rejection remains deceptive and includes varied strategies such as modification of the maintenance regimen, addition of inhaled immunosuppressants and/or total lymphoid irradiation and photopheresis.
Topics: Cyclosporine; Drug Therapy, Combination; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Lung Transplantation; Multicenter Studies as Topic; Mycophenolic Acid; Prospective Studies; Randomized Controlled Trials as Topic; Tacrolimus
PubMed: 14738248
DOI: 10.1183/09031936.03.00039203 -
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 -
Transplantation and Cellular Therapy Mar 2021
PubMed: 33462569
DOI: 10.1016/j.jtct.2021.01.008 -
Frontiers in Immunology 2017Allogeneic hematopoietic stem cell transplant (HSCT) is used to treat increasing numbers of malignant and non-malignant disorders. Despite significant advances in... (Review)
Review
Allogeneic hematopoietic stem cell transplant (HSCT) is used to treat increasing numbers of malignant and non-malignant disorders. Despite significant advances in improved human leukocyte antigens-typing techniques, less toxic conditioning regimens and better supportive care, resulting in improved clinical outcomes, acute graft-versus-host disease (aGvHD) continues to be a major obstacle and, although it principally involves the skin, gastrointestinal tract, and liver, the thymus is also a primary target. An important aim following HSCT is to achieve complete and durable immunoreconstitution with a diverse T-cell receptor (TCR) repertoire to recognize a broad range of pathogens providing adequate long-term adaptive T-lymphocyte immunity, essential to reduce the risk of infection, disease relapse, and secondary malignancies. Reconstitution of adaptive T-lymphocyte immunity is a lengthy and complex process which requires a functioning and structurally intact thymus responsible for the production of new naïve T-lymphocytes with a broad TCR repertoire. Damage to the thymic microenvironment, secondary to aGvHD and the effect of corticosteroid treatment, disturbs normal signaling required for thymocyte development, resulting in impaired T-lymphopoiesis and reduced thymic export. Primary immunodeficiencies, in which failure of central or peripheral tolerance is a major feature, because of intrinsic defects in hematopoietic stem cells leading to abnormal T-lymphocyte development, or defects in thymic stroma, can give insights into critical processes important for recovery from aGvHD. Extracorporeal photopheresis is a potential alternative therapy for aGvHD, which acts in an immunomodulatory fashion, through the generation of regulatory T-lymphocytes (Tregs), alteration of cytokine patterns and modulation of dendritic cells. Promoting normal central and peripheral immune tolerance, with selective downregulation of immune stimulation, could reduce aGvHD, and enable a reduction in other immunosuppression, facilitating thymic recovery, restoration of normal T-lymphocyte ontogeny, and complete immunoreconstitution with improved clinical outcome as the ability to fight infections improves and risk of secondary malignancy or relapse diminishes.
PubMed: 28377772
DOI: 10.3389/fimmu.2017.00328 -
Advances in Experimental Medicine and... 2017Ultraviolet blood irradiation (UBI) was extensively used in the 1940s and 1950s to treat many diseases including septicemia, pneumonia, tuberculosis, arthritis, asthma... (Review)
Review
Ultraviolet blood irradiation (UBI) was extensively used in the 1940s and 1950s to treat many diseases including septicemia, pneumonia, tuberculosis, arthritis, asthma and even poliomyelitis. The early studies were carried out by several physicians in USA and published in the American Journal of Surgery. However with the development of antibiotics, UBI use declined and it has now been called "the cure that time forgot". Later studies were mostly performed by Russian workers and in other Eastern countries and the modern view in Western countries is that UBI remains highly controversial.This chapter discusses the potential of UBI as an alternative approach to current methods used to treat infections, as an immune-modulating therapy and as a method for normalizing blood parameters. No resistance of microorganisms to UV irradiation has been reported, and multi-antibiotic resistant strains are as susceptible as their wild-type counterparts. Low and mild doses of UV kill microorganisms by damaging the DNA, while any DNA damage in host cells can be rapidly repaired by DNA repair enzymes. However the use of UBI to treat septicemia cannot be solely due to UV-mediated killing of bacteria in the blood-stream, as only 5-7% of blood volume needs to be treated with UV to produce the optimum benefit. UBI may enhance the phagocytic capacity of various phagocytic cells (neutrophils and dendritic cells), inhibit lymphocytes, and oxidize blood lipids. The oxidative nature of UBI may have mechanisms in common with ozone therapy and other oxygen therapies. There may be some similarities to extracorporeal photopheresis (ECP) using psoralens and UVA irradiation. However there are differences between UBI and ECP in that UBI tends to stimulate the immune system, while ECP tends to be immunosuppressive. With the recent emergence of bacteria that are resistant to all known antibiotics, UBI should be more investigated as an alternative approach to infections, and as an immune-modulating therapy.
Topics: Animals; Bacteria; Bacterial Infections; Bacterial Load; Blood; DNA Damage; DNA, Bacterial; Humans; Microbial Viability; Photopheresis; Treatment Outcome; Ultraviolet Rays; Ultraviolet Therapy
PubMed: 29124710
DOI: 10.1007/978-3-319-56017-5_25 -
The Yale Journal of Biology and Medicine 1989Photopheresis, the process by which peripheral blood is exposed in an extracorporeal flow system to photoactivated 8-methoxypsoralen (8-MOP), is a new treatment for... (Review)
Review
Photopheresis, the process by which peripheral blood is exposed in an extracorporeal flow system to photoactivated 8-methoxypsoralen (8-MOP), is a new treatment for disorders caused by aberrant T lymphocytes. It is now a standard therapy for advanced cutaneous T-cell lymphoma and shows promise in the treatment of two autoimmune disorders, pemphigus vulgaris and progressive systemic sclerosis (scleroderma). Additional diseases for which clinical trials are in progress include multiple sclerosis, organ transplant rejection, rheumatoid arthritis, and AIDS. The mechanism of action appears to involve a "vaccination" against the pathogenic T cells, in a clone-specific manner. Photoactivated 8-MOP initiates a cascade of immunologic events by forming covalent photoadducts with nuclear and cell surface-adherent DNA and possibly with other cellular molecules. For reasons not yet fully clarified, but probably related to enhanced cycling of the T-cell receptor for antigen, photopheresis increases the immunogenicity of the irradiated T cells so that their reinfusion induces a therapeutically significant immunologic reaction that targets unirradiated T cells of the pathogenic clone(s). The specificity of the induced immunologic reaction probably results from the extremely disproportionate expansion of the pathogenic clone(s), relative to the several million other clones of normal T cells.
Topics: Autoimmune Diseases; Extracorporeal Circulation; Humans; Lymphoproliferative Disorders; Methoxsalen; PUVA Therapy; T-Lymphocytes
PubMed: 2700056
DOI: No ID Found -
Biomedicines Oct 2017Although significant advances have been made in the biologic understanding of graft-versus-host disease (GVHD) and its treatment options, GVHD remains the single most... (Review)
Review
Although significant advances have been made in the biologic understanding of graft-versus-host disease (GVHD) and its treatment options, GVHD remains the single most challenging obstacle to the success of allogeneic hematopoietic cell transplantation (HCT) due to high risk of disabling morbidity and mortality. Extracorporeal photopheresis (ECP) has promising effects in controlling steroid-refractory GVHD, both acute and chronic, and it has been studied extensively. Its putative immunomodulatory mechanisms, while not immunosuppressive, position ECP as an attractive treatment strategy for GVHD patients who are already receiving global immunosuppression. However, ECP is relatively underutilized due in part to limited access and time commitment. Here, we review the recent findings on the ECP efficacy in both acute and chronic GVHD, primarily for steroid-refractory status, and we critically appraise its benefits. We also explore salient considerations on the optimal use of ECP in the treatment of refractory GVHD.
PubMed: 29019937
DOI: 10.3390/biomedicines5040060 -
The Yale Journal of Biology and Medicine Mar 2020Dendritic cells (DCs) are professional antigen-presenting cells, necessary for the initiation and maintenance of antigen-specific immunity and tolerance. Decades of... (Review)
Review
Dendritic cells (DCs) are professional antigen-presenting cells, necessary for the initiation and maintenance of antigen-specific immunity and tolerance. Decades of research have been driven by hopes to harness the immunological capabilities of DCs and achieve physiological partnership with the immune system for therapeutic ends. Potential applications for DC-based immunotherapy include treatments for cancer, autoimmune disorders, and infectious diseases. However, DCs have poor availability in peripheral and lymphoid tissues and have poor survivability in culture, leading to the development of multiple strategies to generate and manipulate large numbers of DCs . Among these is Extracorporeal Photopheresis (ECP), a widely used cancer immunotherapy. Recent advancements have uncovered that stimulation of monocyte-to-DC maturation via physiologic inflammatory signaling lies at the mechanistic core of ECP. Here, we describe the landscape of DC-based immunotherapy, the historical context of ECP, the current mechanistic understanding of monocyte-to-DC maturation in ECP, and the implications of this understanding on making scientifically driven improvements to modern ECP protocols and devices.
Topics: Dendritic Cells; Humans; Immunotherapy; Neoplasms; Photopheresis
PubMed: 32226344
DOI: No ID Found