Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extracorporeal photophoresis (ECP), a therapeutic modality that has been under investigation for some years, is based on separation of a leucocyte/lymphocyte-enriched cell fraction from the peripheral blood, extracorporeal treatment of the cells with 8-MOP/UVA and subsequent reinfusion of the cells in the patient. Its main effects seem to consist in changes to the immunologic behaviour of the photoinactivated/modulated cells. The immune response of the host is obviously stimulated by this treatment. ECP is normally performed for 4 h per day on 2 consecutive days every 4 weeks. The treatment is well tolerated and causes few side effects. In our department, 1210 ECP treatments were administered to 41 patients between 1990 and 1994 and a preliminary evaluation was performed. These patients included 21 with cutaneous T-cell lymphoma (CTCL), 10 with progressive systemic scleroderma, 4 with chronic graft-versus-host disease and 1 each with pemphigus vulgaris, epidermolysis bullosa acquisita, lupus erythematosus and cutaneous mucinosis. Patients with erythroderma and preserved immunocompetence achieved the best responses of all patients with CTCL. A treatment combining ECP with rIFN-alpha, PUVA and/or radiation was also successful in patients with tumour-stage CTCL and lymph node involvement. Progressive systemic scleroderma responded in more than 50% of our cases. Treatment results were impressive in 4 patients with chronic graft-versus-host disease presenting with sclerodermatous and lichenoid changes of the skin and mucous membranes. A clear improvement was also observed in the patient with pemphigus vulgaris refractory to standard therapies and in another patient with scleromyxoedema (Arndt-Gottron syndrome). The effectiveness of ECP seems to be quite well established in CTCL, but remains to be examined in autoimmune dermatoses. ECP is an attractive addition to the dermatological therapies available but our experience is still preliminary.
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PMID:[Therapeutic experiences with extracorporeal photopheresis. Technical procedure, follow-up and clinical outcome in 31 skin diseases]. 886 55

Recently various cytokines have been introduced into the clinic and have played important therapeutic roles in the treatment of hematological malignancies. Among these cytokines, I have focused on interferon (IFN) and granulocyte (G) or granulocyte-macrophage (GM) colony stimulating factor (CSF), which are currently the most useful cytokines, in this review. IFN-alpha has been approved for chronic myelogenous leukemia (CML), multiple myeloma and hairy cell leukemia. In addition, IFN-alpha has therapeutic potentials for low grade non-Hodgkin's lymphoma, cutaneous T cell lymphoma and adult T cell leukemia/lymphoma. Thus, IFN-alpha is one of the most useful and wide-ranging antitumor agents in hematological malignancies. Most striking effects have been studied in chronic phase CML. Cytogenetic responses are seen in 30-40% of the treated patients and a complete cytogenetic response can be seen in about 10%. Long-term survival can be expected in these patients. Considering the risk of graft-versus-host disease-associated mortality in allogeneic bone marrow transplantation, the category of treatment is difficult to choose in IFN-responsive patients. Elucidation of the antitumor mechanism of IFN, as a prototype for other biological response modifiers, may revolutionize cancer treatment. G- and GM-CSF (CSFs) have reduced the duration of neutropenia, incidence of infectious episodes and days of hospitalization following cancer chemotherapy or stem cell transplantation. CSFs have also been used to mobilize peripheral blood stem cells and to increase dose intensity of chemotherapeutic agents. Leukemic cells from many patients with acute myelogenous leukemia (AML) have surface receptors for CSFs and may proliferate in response to CSFs. However, several randomized studies showed that CSFs can be used safely and effectively in augmenting neutrophil recovery in patients with AML when given after induction chemotherapy. Various trials have been made to prime leukemic cells by CSFs to make them more susceptible to chemotherapy, but no convincing evidence has been obtained.
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PMID:Cytokine therapy for hematological malignancies. 899 Jun 22

Lupus erythematosus (LE) is a disease with a wide spectrum of cutaneous and systemic manifestations. Discoid LE (DLE) is the most common form of cutaneous LE; the disseminated form of DLE is rare. We report an encouraging response to treatment with extracorporeal photopheresis (ECP) in a single patient with disseminated DLE who did not respond to conventional therapy. To the best of our knowledge this is the first successful use of ECP in the management of such a patient. Extracorporeal photopheresis is a therapeutic modality that has been under investigation for more than 12 years. Although originally developed for the treatment of cutaneous T-cell lymphoma, ECP has recently been used for the management of autoimmune diseases including systemic scleroderma, pemphigus vulgaris and SLE, as well as prevent organ rejection in patients with cardiac or kidney transplants and graft versus host disease after bone marrow transplantation.
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PMID:[Extracorporeal photopheresis in therapy-refractory disseminated discoid lupus erythematosus]. 967 77

Extracorporeal exposure of peripheral blood mononuclear cells to the photosensitizing compound 8-methoxypsoralen and ultraviolet A radiation has been shown to be effective in the treatment of several T-cell-mediated diseases, including cutaneous T-cell lymphoma and rejection after organ transplantation. We present 21 patients (10 men and 11 women) with hematological malignancies with a median age of 36 years (range, 25 to 55 years) who had received marrow grafts from sibling (n = 12) or unrelated (n = 9) donors. Six patients had acute graft-versus-host disease (GVHD) grade II to III not responding to cyclosporine A (CSA) and prednisolone when referred to extracorporeal photochemotherapy (ECP). In 15 patients, 2 to 24 months after bone marrow transplantation (BMT), extensive chronic GVHD with involvement of skin (n = 15), liver (n = 10), oral mucosa (n = 11), ocular glands (n = 6), and thrombocytopenia (n = 3) developed and was unresponsive to conventional therapy, including steroids. All patients were treated with ECP on 2 consecutive days every 2 weeks for the first 3 months and thereafter every 4 weeks until resolution of GVHD. ECP was tolerated excellently without any significant side effects. After a median of 14 cycles of ECP, acute GVHD resolved completely in 4 of 6 patients (67%) and partially in another 2 patients. Cutaneous chronic GVHD completely resolved in 12 of 15 (80%) patients. Contractures of knees and elbows due to scleroderma resolved partially. Oral mucosal ulcerations resolved in all patients. Seven of 10 patients (70%) with liver involvement had complete responses after ECP. After discontinuation of ECP, no severe infections were observed. Our findings suggest that ECP is a safe and effective adjunct therapy for both acute and extensive chronic GVHD with skin and visceral involvement and resistance to conventional therapy.
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PMID:Successful use of extracorporeal photochemotherapy in the treatment of severe acute and chronic graft-versus-host disease. 978 44

Photopheresis or extracorporeal photochemotherapy (ECP) is a novel immunomodulatory therapy based upon pheresis of light-sensitive cells. Whole blood is removed from patients who have previously ingested the photosensitizing agent 8-methoxypsoralen (8-MOP) followed by leukapheresis and exposure of the 8-MOP containing white blood cells (WBCs) extracorporeally to an ultraviolet A (UVA) light source prior to their return to the patient. In 1988, the Food and Drug Administration (FDA) approved photopheresis for the treatment of cutaneous T-cell lymphoma (CTCL). Treatment of CTCL with photopheresis has been reported in over 300 patients worldwide. Photopheresis has also demonstrated encouraging results in the treatment of solid organ transplant rejection, graft versus host disease, scleroderma, and other autoimmune diseases although fewer patients have been studied. This review will focus on the North American experience with photopheresis.
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PMID:The North American experience with photopheresis. 1060 33

Extracorporeal photochemotherapy (ECP) is an immunotherapy that has found a role in the therapy of cutaneous T cell lymphoma, a disease of mature activated T cells. Graft-versus-host disease (GVHD) is also mediated by activated T cells, and thus often responds to therapies that target T cells. Murine models for both GVHD and ECP can be combined to study the impact of this immunotherapy on GVHD. In this paper we present a patient with GVHD who demonstrated a beneficial therapeutic response to treatment with ECP. The findings of this case are compared with the observations from a murine model for GVHD-ECP. The potential mechanisms of ECP in the treatment of GVHD are discussed. along with the similarities observed with ECP in the treatment of other conditions.
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PMID:Extracorporeal photochemotherapy in human and murine graft-versus-host disease. 1009 1

Extracorporeal photochemotherapy was developed for treatment of cutaneous T-cell lymphoma (CTCL). Several independent and multicenter trials using lymphapheresis with 8-methoxypsoralen (8-MOP) activated by shortwave ultraviolet light have demonstrated the clinical benefit of this modality for treatment of advanced CTCL. Recently, trials using the combination of photochemotherapy and recombinant interferons or photochemotherapy and low doses of methotrexate have been initiated to enhance the response to photopheresis. Also, a multicenter study evaluating a new 8-MOP formulation that could be added into the leukocyte/plasma fractions prior to ultraviolet exposure is in progress in CTCL patients. The applications of photochemotherapy in the treatment of other disorders of T-cells are being examined in ongoing clinical trials. Pilot studies have been completed and controlled trials are under way in patients with autoimmune diseases. Important information has emerged regarding the potential use of photopheresis for prevention of solid organ allograft rejection. Several investigators have undertaken pilot studies comparing the efficacy of photochemotherapy with the conventional immunosuppressive therapy for treatment of cardiac transplant rejection. It is hoped that photochemotherapy can induce an immune tolerance in the allograft setting and therefore eliminate or reduce the use of cyclosporin. Other considerations have led to the use of photochemotherapy in the prevention and treatment of graft-versus-host disease after alloeneic and unrelated donor marrow transplantation. Randomized studies are required to evaluate the impact of photochemotherapy on the course of graft-versus-host disease and overall survival.
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PMID:Extracorporeal photochemotherapy: a scientific overview. 1015 61

Extracorporeal photopheresis (ECP) is used in the treatment of T-cell-mediated disorders. However, the mechanism by which ECP achieves its effect remains illusive. Over recent years the ability of ECP to induce apoptosis has been demonstrated by cell culture experiments and retrospective histological analysis. We investigated if apoptosis could be determined in samples tested ex vivo from the UVAR:ECP system. Lymphocytes from 11 patients (six with cutaneous T-cell lymphoma, four with graft-versus-host disease, and one with scleredema) were isolated at three stages of the ECP process: immediately before ECP treatment, from the first buffy coat collected, and post UV irradiation, prior to re-infusion. Using flow cytometry each stage was tested for the early apoptotic markers; Annexin V, ApoptestTM and Carboxy-SNARF-1-AM. Comparisons of the pre-ECP and pre-infusion samples demonstrated a significant increase in apoptotic lymphocytes for all three flow cytometric techniques (P < 0.01). Increases between the pre-ECP and first buffy coat, used as a measure of the extracorporeal manipulation, were much lower. These results demonstrate that ECP directly induces significant levels of apoptosis in lymphocytes of CTCL, GvHD and scleredema patients. The apoptosis of these lymphocytes may contribute to the ECP effect.
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PMID:Extracorporeal photopheresis induces apoptosis in the lymphocytes of cutaneous T-cell lymphoma and graft-versus-host disease patients. 1060 73

Advances in posttransplant immunosuppression have to the present not been able to prevent the development of graft-versus-host disease (GVHD) in patients given related or unrelated stem cell grafts for cure of hematologic diseases. Patients with GVHD not responding to first line therapy with corticosteroids remain at high risk of death due to severe infections or organ failure. Extracorporeal exposure of peripheral blood mononuclear cells to the photosensitizing agent 8-methoxypsoralen and ultraviolet A radiation has been shown to be effective in treatment of selected T-cell mediated diseases, including cutaneous T-cell lymphoma and rejection after organ transplantation. Extracorporeal photochemotherapy (ECP) is also a safe and efficacious adjunct therapy for both acute and chronic extensive GVHD with skin and visceral involvement and resistance to conventional immunosuppressive therapy. A multicenter randomized study should help define the impact of ECP in the treatment of GVHD and overall survival of these patients.
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PMID:Extracorporeal photochemotherapy in the treatment of severe graft-versus-host disease. 1078 86

Dermatologists are frequently involved in the management of cutaneous T-cell lymphoma (CTCL) and graft-versus-host disease (GVHD). The similarities of these two entities are reviewed in the context of clinical and histologic findings, pathogenesis, and therapy. Photopheresis therapy (extracorporeal photochemotherapy) is used in the treatment of both entities, and the mechanisms underlying the responses represent yet another striking similarity of these two crippling dermatologic diseases.
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PMID:Cutaneous T-cell lymphoma and cutaneous graft-versus-host disease. Two indications for photopheresis in dermatology. 1094 37


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