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)

Cyclosporin A was given to five patients with acute leukaemia in whom graft-versus-host disease (G.V.H.D.) had developed after bone-marrow transplantation from sibling donors. In all instances the acute erythematous skin reaction of G.V.H.D. resolved within two days, but four of the five patients died. Cyclosporin A in high doses produced anorexia, nausea, and a reversible rise in blood-urea. The four patients who died all had liver damage, but the histological changes varied. Cyclosporin A modifies the acute skin reaction of G.V.H.D. In the management of liver and gut G.V.H.D., and in prophylaxis of G.V.H.D., its role needs to be determined.
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PMID:Cyclosporin A for the treatment of graft-versus-host disease in man. 8 37

Cyclosporin A (CsA) is a potent inhibitor of cytokine (IL-2-IL-6, IFN gamma) production by CD4+ T lymphocytes stimulated via the T cell antigen receptor pathway. This action results in indirect inhibitory effects on the growth and differentiation of B lymphocytes (IL-4 and IL-6). Using experimental models, it has also been shown that the functional activities of mononuclear phagocytes (IFN-gamma) and other antigen-presenting cells, production of mast cells (IL-3) and eosinophils (IL-5) and the activity of natural killer (NK) cells may be inhibited indirectly by CsA. In addition, however, CsA blocks B cell responses to Ca(2+)-dependent signals (e.g., anti-IgM) downstream of phosphatidyl inositol diphosphate hydrolysis; Ca(2+)-independent responses (e.g., to LPS or IL-4) are largely unaffected. In general terms, the functions of macrophages are unchanged or reduced in the presence of CsA. These include phagocytic activity in vitro and in vivo, chemotactic migration, superoxide and H2O2 production, protein (including monokine) secretion and MHC gene product expression. Antigen presentation (e.g., by epidermal Langerhans cells) may be affected, especially at high drug concentrations. There is recent evidence that CsA inhibits mediator (histamine and prostaglandin) release from human mast cells and that mucosal mast cell numbers may be diminished in CsA-treated animals exhibiting graft-versus-host disease or helminth infections.
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PMID:The effects of cyclosporin A on non-T cell components of the immune system. 150 9

The presence of two distinct T-cell receptors (TCR) alpha/beta and gamma/delta dimers as well as of the activated T cells was analysed in peripheral blood mononuclear cells from seventeen recipients of allogeneic bone marrow transplants for leukemia and for severe aplastic anemia. Nine of seventeen recipients expressed an elevated percentage of T cells bearing TCR gamma/delta receptors in their peripheral blood. Seven out of nine cases having elevated gamma/delta positive cells showed chronic graft-versus-host (GVH) disease; one patient was treated with Cyclosporin A, and one patient was asymptomatic. In the twelve patients with GVH or other clinical symptoms, activated T cells (CD3+/HLA-DR+) were elevated indicating an autoreactive or alloreactive cell population. Our results confirmed earlier in vitro data showing that TCR-gamma/delta-bearing lymphocytes may be an activated T-cell population, and this T cell subset might be involved in mediating GVH disease, or in prolonging immunodeficiency after transplantation.
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PMID:TCR gamma/delta bearing lymphocytes in peripheral blood of allogenic bone marrow transplanted patients. 153 60

A 9-year-old boy was admitted with the diagnosis of myelodysplastic syndrome (FAB RAEB in T). The patient was treated with busulfan and cyclophosphamide and transplanted with bone marrow cells from an HLA identical sister. Cyclosporin A (CyA) and short term methotrexate (MTX) was given for prophylaxis against graft versus host disease (GvHD). The serum potassium value was observed to increase to 6.3 mEq/l during the period of CyA therapy. The serum potassium value returned to 4 mEq/l when CyA treatment was decreased to a serum concentration of less than 50 ng/ml (FPIA). On day 90 post transplantation the patient was diagnosed as relapsed. The patient was preconditioned with cyclophosphamide and total body irradiation and a second bone marrow transplantation was performed using cells from the same donor. He was treated again with CyA and short term MTX for the prevention of GvHD. Once again the patient became hyperkalemic with 6.8 mEq/l. The serum creatinine level was 0.9 mg/dl, the GFR was 52.1 ml/min, FEK was 7.1%. Pseudohypoaldosteronism or hyporeninemic hypoaldosteronism was suspected. To investigate this possibility a renin/aldosterone stimulation test was performed. We speculate that an idiosyncratic response to CyA resulted in pseudohypoaldosteronism and produced a defect in potassium secretion.
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PMID:[Hyperkalemia in a cyclosporine A-treated allogeneic bone marrow transplant recipient]. 154 16

Cyclosporin A, a strong immunosuppressive agent, has been used to prevent rejection or graft-versus-host disease (GVHD) after organ transplantations including bone marrow transplantations. Monitoring of cyclosporin A concentration in whole blood is necessary for its high frequency of side effects. The authors to measured its concentration by means of radioimmunoassay (RIA) as well as fluorescence polarization Immunoassay (FPIA) a cases after bone marrow transplantation. There was a good correlation between these two methods. FPIA is less specific for cyclosporin A than RIA, but it is an easier method. It is important to measure the concentration of cyclosporin with FPIA because there are metabolites of cyclosporin A which cannot be measured with RIA. Thus FPIA can be applied to the routine monitoring of cyclosporin.
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PMID:[Monitoring of cyclosporin A concentration in whole blood with fluorescence polarization immunoassay after bone marrow transplantation]. 160 2

Interleukin-2 (IL-2) therapy generates killer cells with major histocompatibility complex (MHC)-unrestricted cytotoxicity against most tumors but not normal tissues. Cyclosporine A (CsA) has been reported to break tolerance to self and to induce killer cells with specificity against class II MHC (Ia) antigens both on the host and the tumor cells, resulting in a mild graft-versus-host disease (GVHD) in an autologous bone marrow transplantation (BMT) setting in the rat. We used these two agents in a syngeneic BMT model in a strain of mice that does not develop GVHD with CsA. Therapy with either agent alone was ineffective, whereas a combination of CsA plus IL-2 after BMT induced a potent graft-versus-tumor (GVT) effect against a melanoma and an acute myeloid leukemia. The antitumor effect could be adoptively transferred by infusing spleen cells harvested from mice treated with CsA plus IL-2 into secondary recipients that received chemoradiotherapy. The cytotoxicity of these cells was not influenced by treatment of tumor cells with gamma-interferon or Ia antibody. The cytotoxic effect was mediated by Thy 1+ and asialo GM 1+ cells. There was no GVHD either in the primary recipients of CsA and IL-2 or in those receiving the adoptively transferred spleen cells. Our findings show that combination therapy with CsA and IL-2 after syngeneic BMT induces a potent GVT effect in a non-MHC-restricted manner, and point to the existence of differences between the mechanisms of GVT and GVHD.
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PMID:Synergism of interleukin-2 and cyclosporine A in induction of a graft-versus-tumor effect without graft-versus-host disease after syngeneic bone marrow transplantation. 161 Oct 84

CBA/N mice submitted to autologous bone marrow reconstitution after lethal irradiation and simultaneous Cyclosporin A (CsA) treatment develop a chronic graft-versus-host disease with autoimmune characteristics. When compared to normal controls, diseased mice show an overrepresentation of V beta 8-expressing T cells (65-80% of all CD3+ lymphocytes), together with a marked increase in the titres of serum Ig that specifically bind to F(ab')2 fragments of anti-V beta 8 F23.1 antibodies. Such 'V beta 8-like' Ig V regions are abundantly represented among the IgG2b and mAbs of an unselected collection of hybridomas derived from these mice. These mAbs are not multireactive Ig as they fail to bind to a panel of various antigens and antibodies, but often show simultaneous reactivity with anti-idiotypic mAbs to F23.1 and auto-binding. These molecules may provide the structural basis of V-region specific complementarities, driving the expansion of restricted T and B cell repertoires associated with pathological autoimmunity.
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PMID:Selective expansion of idiotype sharing T and B cells in cyclosporin A-mediated autoimmunity. 171 75

Lethally irradiated rats, reconstituted with syngeneic bone marrow and given Cyclosporin A (CyA) for 6 weeks, developed disease resembling allogeneic graft-versus-host disease 2 weeks after withdrawal of CyA. Other studies have demonstrated the pivotal role of the thymus in the etiology of this CyA-induced autoimmune disease (CyA-AI). In this study the question was addressed whether inducer/effector cells of CyA-AI are generated in the thymus during or after CyA administration; whether these cells stay in the thymus, or, if they don't, whether they home to the secondary lymphoid organs. Adoptive transfer of thymocytes from donors treated for induction of CyA-AI obtained one and 14 days after cessation of CyA administration did not elicit CyA-AI in irradiated secondary recipients. Furthermore, adult thymectomy of rats immediately after the course of CyA did not influence the kinetics of development of skin pathology, although weight loss commenced later in thymectomized than in sham-thymectomized rats. Lymph node and spleen cells obtained from donors treated for induction of CyA-AI one and 14 days after withdrawal of CyA-AI caused CyA-AI upon adoptive transfer to secondary recipients, but the symptoms of acute disease (dermatitis, alopecia and weight loss) were strikingly less severe upon transfer of lymphoid cells obtained one day after stopping CyA than 14 days thereafter. Therefore, this study demonstrates that CyA-AI inducer/effector cells are generated in the thymus during the administration of CyA. These cells exit from the thymus during CyA administration; either they home predominantly peripherally (i.e. in the skin) rather than in the secondary lymphoid organs, or they leave the thymus as inducer cells which home in the lymphoid organs where they subsequently may trigger potentially autoreactive lymphocytes as probably also present in normal individuals, or both pathways may be operative.
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PMID:On the localization of effector cells in cyclosporin-induced autoimmunity. 177 63

The treatment of severe aplastic anemia has been modified recently by the demonstration that Cyclosporine A is active alone or in combination leading to more than 50% response rate. Combination or sequential treatments with ATG seem to be better than such drug separately but this must be studied in randomized studies. Long term follow-up is necessary to assess the rate of malignant transformation. Growth factors have been recently introduced. G or GM-CSF seem to be active. IL-3 has not been proven to be effective in very small non randomized study. Allogeneic bone marrow transplantation is the best treatment with a matched related donor, progress must be achieved in methods of conditioning and GVH prophylaxis when a matched unrelated donor is used.
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PMID:Recent treatments of aplastic anemia. The International Group on SAA. 181 8

Five of 182 recipients of allogeneic bone marrow transplants performed between 2/84 and 6/90 developed seizures while receiving cyclosporine and methylprednisolone to prevent acute graft-versus-host disease. All received a radiation-free regimen of busulfan and cyclophosphamide as preparative therapy. Two patients received HLA-mismatched allografts; and three patients received marrow from HLA-identical sibling donors. Two patients had received extensive intrathecal therapy prior to transplantation. All patients were receiving standard prophylactic doses of CsA and MP at the time of onset (median 31 days posttransplantation) of seizures. Three patients had mild-to-moderate hypertension and varying degrees of morphologic evidence of microangiopathic hemolytic anemia. None had unusually low magnesium levels. Cyclosporine levels were not in the toxic range. Cranial magnetic resonance imaging and computed tomography (CT) showed bilateral abnormalities primarily in the posterior temporal, occipital, and parietal lobes. These abnormalities were shown to be transient on sequential MRI exams in two patients. Seizures as well as radiologic abnormalities resolved on stopping CsA and did not recur in 2 patients who subsequently received CsA in lower doses. These findings confirm and expand previous observations of CsA-associated seizures and demonstrate that they occur in allogeneic bone marrow transplant recipients following a radiation-free preparative regimen of busulfan and cyclophosphamide.
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PMID:Cyclosporine-associated seizures in bone marrow transplant recipients given busulfan and cyclophosphamide preparative therapy. 187 5


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