[Update on extracorporeal photopheresis]. / Update zur extrakorporalen Photopherese.

Extracorporeal photopheresis (ECP) is a treatment approach that combines leukapheresis with photochemotherapy and is derived from PUVA; with this procedure, nucleated cells such as lymphocytes and monocytes are extracorporeally irradiated with UVA light after photosensitization. ECP is an effective treatment modality with few side effects that in recent years has been expanded to treat a range of indications. It has been proven effective in the treatment of cutaneous T cell lymphoma and is being increasing used in other lymphocyte-mediated, autoimmune and inflammatory diseases that are associated with proliferation of autoreactive T cells.

A concise review on extracorporeal photochemotherapy: Where we began and where we are now and where are we going!

Currently, more than 1080 peer-reviewed papers are displayed on PubMed when initiating a search for therapeutic indications and mechanisms of action of extracorporeal photochemotherapy (ECP). This concise review focuses mainly on some prevalent and traditional treatment-resistant disorders with an emphasis on immunologic complications emerging from stem cell and solid organ transplantation.

Extracorporeal photopheresis: technique, established and novel indications.

Extracorporeal photopheresis (ECP) has had a major impact in the treatment of various conditions in the past 25 years. Although it was initially developed for the treatment of patients with resistant cutaneous T cell lymphoma (CTCL), this therapy was later used to treat recipients of solid organs and stem cell transplants with rejection or graft-versus-host disease (GVHD), respectively. A significant number of patients with CTCL can achieve long term remission with ECP therapy. Those patients with heart or lung transplants may experience fewer or shorter rejection episodes following ECP. Furthermore, patients that respond to ECP can generally reduce the dose of immunosuppression medication, thus minimizing the morbidity caused by drugs such as corticosteroids and calcineurin inhibitors. While the exact mechanism of action of ECP is not well-understood, evidence suggests that reinfusion of the patient's apoptotic white blood cells, the ultimate product of ECP, promotes immunomodulatory events that are beneficial in patients with CTCL, transplant rejection, GVHD, and possibly other inflammatory conditions.

Extracorporeal photopheresis: clinical use so far.

Extracorporeal photopheresis (ECP or photopheresis) is an advanced therapeutic apheresis procedure in which blood is separated into its various components and the isolated buffy coat is treated with 8-methoxypsoralen (a photoactivating drug), exposed to ultraviolet light and returned to the patient. All other remaining blood components are also returned to the patient. The purpose of this procedure is immunomodulation. The treated leukocytes, specifically T-cells, are returned to the patient's circulation and will induce cytotoxicity and reduce proliferation of new T-cells. In the United States, ECP was initially approved for the treatment of cutaneous T-cell lymphoma by the US Food and Drug Administration in the late 1980s. Since that time, it has been used as an "off-label" therapy to treat several other autoimmune diseases in the United States and even more extensively in Europe and Asia. The following review is limited to the current clinical use of ECP in cutaneous T-cell lymphoma, Crohn's disease, systemic sclerosis, graft versus host disease, and emerging data on nephrogenic systemic fibrosis.

[New therapeutic prospects for renal transplant: extracorporeal photochemotherapy]. / Nuove prospettive terapeutiche per il trapianto di rene: la fotochemioterapia extracorporea.

Since 1960, different classes of immunosuppressive drugs have been used in the post-transplant follow-up. Each is assessed for its effectiveness in preventing rejection but also on the basis of the many side effects induced by prolonged treatment. To reduce these side effects, continuous development of knowledge and medical technology to create cutting-edge therapies in the field is necessary. One of these is extracorporeal photochemotherapy (ECP), an immunomodulatory therapy approved by the United States Food and Drug Administration in 1988 for the treatment of advanced forms of cutaneous T-cell lymphoma. EC P is a useful therapeutic tool for the development of immunomodulation supported by CD8+ clone-specific cytotoxic lymphocytes. The T cells targeted by EC P are modified by photoactivation and seem to develop marked immunogenicity with no suppression of the immune response. Recent studies suggest the possible utility of EC P in the treatment of glomerulonephritis and in countering rejection after transplantation of organs including the kidney.

Beyond dialysis: current and emerging blood purification techniques.

Extracorporeal blood purification using various techniques and hardware is a major part of the modern day practice of clinical nephrology. Although the various modalities of hemodialysis and hemofiltration are the most commonly used extracorporeal therapies in clinical nephrology, blood purification using other techniques have become necessary to remove pathogenic, toxic, or waste substances not easily cleared by hemodialysis or hemofiltration due to factors such as molecular size, protein binding, and lipid solubility. The following review is an up to date summary of extracorporeal therapies, beyond hemodialysis and hemofiltration, in current clinical use as practiced by nephrologists and others in the United States and beyond. This comprises therapeutic apheresis (plasma exchange and cytapheresis), plasma adsorption, hemoperfusion, and the bio-artificial devices.

Photopheresis in the treatment of cutaneous T-cell lymphoma: current status.

Cutaneous T-cell lymphoma is the overall name for a group of malignancies in which malignant T-lymphocytes localize at the skin. Of the current 20 recognized subtypes of the disease, the most common are mycosis fungoides and Sézary syndrome. Extracorporeal photopheresis (ECP), an immunomodulating procedure that treats pheresed blood with a photoactive agent, received US Food and Drug Administration approval in 1988 as a medical device for the treatment of CTCL patients, one of many treatment options for such patients. This was followed in 2003 by guidelines in the United Kingdom that recommended ECP for patients with advanced CTCL, particularly after skin-directed treatment options have failed. ECP is now under investigation for use in patients with earlier stages of CTCL. This article reviews the evolution of the ECP technique--for example, the most recent generation of the device requires a lower extracorporeal volume of blood than the previous version did, thus making it possible for more patients to be candidates for the procedure. In addition, there has been progress in understanding how ECP works at the cellular level.

Update on extracorporeal photopheresis in heart and lung transplantation.

Transplant rejection of solid organs remains a threat to thousands of patients despite modern immunosuppressive regimens. The currently available drugs are associated with severe complications such as hypertension, diabetes mellitus, renal failure, risk of infections, and malignancies among many others and, often enough, still allow episodes of rejection. New and less-toxic immunologic measures are desperately needed to accomplish the desired tolerance to the transplant without the undesirable side effects. Extracorporeal photopheresis (ECP) has been shown to benefit especially patients with cardiac transplants, but also those who received lung allografts. ECP likely modulates the recipient's antigen-specific immune responses and inflammation in transplantation by in vivo generation of apoptotic leukocytes. This review will highlight the need for ECP, how it is thought to act, and the published evidence for its role in cardiac and pulmonary transplantation.

Extracorporeal photopheresis: past, present, and future.

Extracorporeal photopheresis (ECP) is a leukapheresis-based therapy that uses 8-methoxypsoralen and ultraviolet A irradiation. Used alone or in combination with biological agents, ECP is an established and effective therapy for advanced cutaneous T-cell lymphoma. ECP has also shown promising efficacy in a number of other severe and difficult-to-treat conditions, including systemic sclerosis, graft-versus-host disease, prevention and treatment of rejection in solid organ transplantation, and Crohn disease. Furthermore, the use of ECP in some of these conditions may allow a significant reduction in the use of systemic steroids and other immunosuppressants, reducing long-term morbidity and mortality. The accumulated experience shows ECP to be well tolerated, with no clinically significant side effects. Progress is also being made in the search for understanding of the mechanisms of action of ECP, which will ultimately facilitate improvements in the use of this therapy.

[Extracorporeal photopheresis]. / Extrakorporale Photopherese.

Photopheresis, originally developed in dermatology, has become a treatment method accepted across various disciplines. A basic knowledge of photomedicine and photobiology is one of the cornerstones of dermatology. Even if photopheresis is used for indications that are not specifically dermatological, e.g. graft-versus-host disease or Crohn's disease, an experienced dermatologist trained in the use of photopheresis should therefore always be consulted.

Enfermedad de injerto contra huésped crónica tratada con fotoféresis: a propósito de un caso / A case of chronic graft vs host disease treated with photopheresis

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Transimmunization and the evolution of extracorporeal photochemotherapy.

We are now aware that extracorporeal photopheresis (ECP) - in which a patient's leukocytes are isolated, passed through an ultrathin clear plastic plate, and exposed to 8-methoxypsoralen (8-MOP) and ultraviolet A light prior to reinfusion - is a simple and efficient dendritic cell (DC) therapy and the first FDA approved selective immunotherapy for cancer. DCs, as the most effective antigen presenting cells (APCs), are central to many ongoing efforts to stimulate immune responses to cancer cells. Moreover, ECP has not only demonstrated efficacy in the treatment of a T cell malignancy--namely cutaneous T-cell lymphoma (CTCL)--but also in treatment of oligoclonal T-cell-mediated diseases such as graft-versus-host-disease (GVHD) and organ transplant rejection. Recent advances in the understanding of DC/T-cell interactions provide insight into how ECP-induced DCs (EI-DCs) can be utilized to stimulate specific T-cell (i.e. anti-tumor) responses, or down-regulate a pre-existing potent T-cell response. The mechanism of this apparent paradox of EI-DC functionality is likely dependent on several fundamental principles: (1) the status of existing in vivo T-cell reactions, (2) the temporal stage of EI-DC differentiation, and (3) the affinity of the available repertoire of T-cell receptors (TCRs) for the antigen(s) in question. Further investigation into DC/T-cell interactions will help to shape the future of ECP and the ability to optimize this therapy for the desired immune effect. To this end, we are developing and testing Transimmunization to replace conventional ECP.