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)

Paraneoplastic pemphigus is a recently described autoimmune disease characterized by painful mucosal ulceration and polymorphous skin lesions in association with an underlying neoplasm. Distinct autoantibodies bind desmoplakin I, desmoplakin II, bullous pemphigoid antigen and an uncharacterized 190 kDa antigen. A case is presented of paraneoplastic pemphigus that developed after radiotherapy for non-Hodgkin's lymphoma in a 53 year old man. Multiple skin biopsies showed a lichenoid reaction without acantholysis. Immunofluorescence and mucosal biopsies were required to establish the correct diagnosis. Corneal opacities resembling lichenoid graft-versus-host disease and retinal haemorrhages, which developed in the patient, have not been previously documented. Despite high doses of immunosuppressive agents and plasmaphoresis, the patient eventually died from respiratory failure.
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PMID:Paraneoplastic pemphigus triggered by radiotherapy. 859 11

This report documents a case of squamous cell carcinoma (SCC) of the tongue in a child with Fanconi anemia (FA). FA is an autosomal recessive syndrome defined by chromosomal breakage in response to diepoxybutane or mitomycin C in which many patients present with pancytopenia, hypoplastic bone marrow, hyperpigmentation of the skin, skeletal malformations, small stature, hypogonadism, and chromosomal aberrations. Such patients are prone to the development of hematological malignancies and squamous cell carcinoma, especially of the head and neck. Although FA appears to be genetically heterogeneous, all cases display abnormalities of DNA repair. A gene defective in one of the four subsets of FA patients has been defined. Defects in this gene are thought to play a role in the development of neoplasia in FA patients. However, many other factors may also contribute to the development of malignancies, including immune deficiencies, therapeutic strategies, and bone marrow transplantation. This report reviews the association of FA and SCC and highlights the many factors involved in the development of neoplasia within a single patient, including FA, cyclophosphamide, immunosuppression, X-irradiation, and chronic oral graft-versus-host disease. In addition, the human papillomavirus status, although negative, is documented for the first time in such a case.
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PMID:Squamous cell carcinoma of the tongue in a child with Fanconi anemia: a case report and review of the literature. 859 46

We evaluated patients presenting with large and recurrent sterile serosal effusions following bone marrow transplants. From a review of the Minnesota BMT Database from 1974 to 1993, seven patients with unexplained multiple effusions involving two or more of the pleural, pericardial or peritoneal cavities were identified. Patients with veno-occlusive disease (VOD), infections, cardiac insufficiency, tumor relapse and GM-CSF toxicity were excluded. All had onset following engraftment and six occurred before day 100. Unexplained multiple effusions were observed in recipients of allogeneic transplants but not autologous transplants and were found only in patients with acute and/or chronic GVHD. Five of seven patients also had cytomegalovirus (CMV) disease. Multiple effusions appear to be part of the presentation of severe acute or chronic GVHD, often in association with CMV disease in patients who receive allogeneic donor marrow.
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PMID:Unexplained effusions: association with allogeneic bone marrow transplantation and acute or chronic graft-versus-host disease. 1456

During the last 15 years, the techniques to prepare leukocyte-poor cellular blood components greatly improved, as well as our knowledge about the role of leukocytes in many adverse effects of transfusion. These two facts favor the extension of indication of leukocyte-poor blood components. Leukocytes in blood components may be detrimental to their storage, due to their metabolic needs and to their progressive lysis, leading to the release of cytokines. Leukocytes are the exclusive vector in blood of CMV and HTLV viruses. Leukocytes are a key element of the immune modifications induced by transfusion. HLA alloimmunization is favored by the transfusion of large quantities of leukocytes HLA different from the recipient whose immune functions are intact. Conversely, the risk of transfusion associated graft versus host disease is dependent of the transfusion of mature T lymphocytes sharing a partial identity with the recipient, and/or an immune deficient status of the recipient. Between these two extremes, many other effects related to the presence of leukocytes in cellular blood components, as are the transfusion effect observed in transplant recipients, the increased risk for bacterial infection after transfusion, the increased risk for tumor recurrence or the reactivation of virus infections, remain to be fully understood. Despite recent significant improvements, further studies, experimental as well as clinical, will be needed to expand the indications of leukocyte-poor blood components.
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PMID:[Why remove leukocytes from labile blood products in 1995?]. 864 Mar 15

Graft-versus-leukemia (GvL) has been shown to be an important immune-mediated antitumor effect in hematologic malignancies. It is still unknown whether such an immunemediated antitumor effect has clinical implications in patients with solid tumors. A 32-year-old woman with inflammatory breast cancer received a bone marrow transplant (BMT) from her HLA-identical sibling. During graft-versus-host disease (GvHD) cytotoxic T lymphocytes were grown and tested in a chromium-release assay against B and T lymphocytes of the patient and donor and against a panel of breast cancer cell lines. Resolution of liver metastases was observed simultaneously with clinical GvHD in the first weeks after transplant. In addition, minor histocompatibility antigen (MiHA)-specific and major histocompatibility complex (MHC) class I antigen-restricted cytotoxic T lymphocytes recognizing breast carcinoma target cells were isolated from the blood of the patient. Pretreatment of such target cells with tumor necrosis factor (TNF)-alpha but not with interferon (IFN)-alpha or IFN-gamma increased susceptibility of these cells to lysis by cytotoxic T lymphocytes. Clinical course and in vitro results suggest that a graft-versus-tumor (GvT) effect might exist after allogeneic BMT for breast cancer. However, clinical experience on a larger scale would be required to determine the clinical efficacy of GvT effects in patients with solid tumors.
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PMID:Evidence for a graft-versus-tumor effect in a patient treated with marrow ablative chemotherapy and allogeneic bone marrow transplantation for breast cancer. 869 72

Fas (APO-1, CD95) is a type I integral membrane protein initially identified by mAbs that induce apoptotic cell death upon binding to certain tumor cells and its belongs to the TNFR family. Fas is expressed on activated lymphocytes and in various tissues including the liver, lung, intestine, and skin. Molecular cloning of Fas ligand (FasL) revealed that it is a type II integral membrane protein homologous to TNF. FasL is predominantly expressed on activated T and NK cells, and mediates Fas divided by target cell lysis by these effector cells. The Fas/FasL system has been also implicated in the pathogenesis of autoimmune diseases, fulminant hepatitis, GVHD, and AIDS. It has been recently reported that human FasL was released as a 26 kD soluble form from COS cells transfected with human FasL cDNA and activated human T cells. In this communication, metalloproteinase-mediated release of FasL and it's clinical relevance are discussed.
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PMID:[Metalloproteinase-mediated release of human fas ligand]. 874 61

The shortage of HLA-matched sibling donors for bone marrow transplant patients has stimulated interest in the use of alternative donors. As a result, there has been a dramatic increase in the use of autologous marrow transplantation, which avoids the complications of graft-versus-host disease, but may deprive the patient of a potentially beneficial graft-versus-disease response and runs the risk of returning occult tumor cells with the graft. There is increasing evidence that these cells may be associated with disease relapse post-transplant, and many methods have been developed for their removal ex vivo. Combinations of negative and positive selection may achieve elimination of tumor cells to the limits of detection of the most sensitive assays currently available. The marked trend toward the use of autologous grafts derived from blood rather than marrow has raised the question as to whether peripheral blood stem cell (PBSC) preparations should be purged of tumor. Data indicate that these grafts generally contain a lower tumor burden, although the stem cell mobilization procedure may recruit tumor cells into the peripheral circulation. Enrichment of CD34+ cells from apheresis products appears, at present, to be less efficient than from marrow and provides at best about a 2-3 log depletion of tumor. This has prompted proposals to follow positive selection by a small-scale purging procedure. Technical issues, such as preprocessing and pooling of collections prior to purging, remain to be addressed. Ultimately, the development of successful purging procedures for PBSC grafts will simply reemphasize the necessity of improving the efficacy of high-dose therapy.
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PMID:Purging of peripheral blood stem cell grafts. 874 89

Based on the concept of circulating hematopoietic stem cells with indefinite self-renewal capacity that gives rise to all three cell lineages, peripheral blood progenitor cells (PBPCs) have widely replaced the use of bone marrow (BM) progenitors for autologous transplantation purposes in patients with malignant hematological disorders and selected solid tumors. Ex vivo purification of normal CD34+ cell subsets contained in the patient's apheresis product possibly eliminates clonogenic tumor cells, but also serves as a target cell population for gene transduction. Genetic tagging of PBPC autografts has proven that: 1) NEOR gene expression is sustained for more than 18 months and 2) clonogenic tumor cells contaminating the autograft contribute to relapse. A second generation of gene transduction studies includes new treatment strategies such as the induction of chemoprotection (multidrug resistance gene-1), chemotherapy sensitization (p53), cancer vaccination and genetic chemosensitization. Most recently allogeneic PBPC transplantation has successfully been introduced with the intention of improving the graft-versus-leukemia effect without inducing a higher incidence or more severe graft-versus-host disease (GVHD) than what is expected after BM transplantation. Introducing the herpes virus thymidine kinase cDNA into activated donor T cells makes them susceptible to gangciclovir, thus allowing the in vivo inactivation of GVHD-inducing T cells. With the close interaction of molecular genetics and clinical oncology/hematology, genetic engineering of stem cell grafts will lead into a new stage of stem cell transplantation technology.
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PMID:Blood stem cell transplantation and gene therapy of cancer. 874 97

Interleukin 2 (IL-2) stimulates the proliferation of T-cells both in vitro and in vivo. When murine or human peripheral blood (PB) or bone marrow (BM) mononuclear cells are incubated with IL-2 in vitro for 24 hours, cytotoxic T-cells are generated. If these activated cells are infused into mice, the enhanced cytotoxicity continues if low dose IL-2 is administered. This combination of administering activated cells with the subsequent low dose IL-2 infusion results in enhanced tumor cell destruction and improved survival rates in mice with acute myeloid leukemia. The encouraging results of these laboratory experiments prompted the initiation of phase I clinical trials in patients with refractory/relapsed hematologic malignancies and patients with breast cancer (Stages II-IV). Results from these trials demonstrate that stem cell transplantation with IL-2 activated stem cells (either PB or BM) with or without parenteral administration of IL-2 results in hematopoietic reconstitution with mild-to-moderate toxicities. This regimen also generates cutaneous and visceral autologous graft versus host disease (AuGVHD). The majority of our patients with relapsed/refractory hematologic malignancies or breast cancer developed either clinical and/or histological evidence of AuGVHD. Further studies are being conducted to determine if patients who develop AuGVHD experience improved disease-free survival from a possible autologous graft versus tumor (GVT) effect. Current laboratory evaluations include the elucidation of the pathogenesis of AuGVHD and molecular evaluation of the purging efficacy of IL-2.
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PMID:Stem cell transplantation with chemoradiotherapy myeloablation and interleukin-2. 874 4

Graft-versus-host disease (GvHD) is the opposite of graft rejection in that a transplant containing donor lymphocytes attacks the host's skin, liver and gut. This disease can usefully also attack host tumor cells. There is a peculiar distribution of normal tissue targets in epithelial stem cell sites, suggesting that GvHD may be the abnormal counterpart of a physiological growth control system. Efforts to understand how the graft-versus-tumor effect could be therapeutically separated from GvHD require further understanding of the mechanisms involved in GvHD.
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PMID:Does graft-versus-host disease attack epithelial stem cells? 879 68


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