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

Disabling esophageal symptoms ((dysphagia, painful swallowing, and severe restrosternal pain) developed in 8 of 63 patients with chronic graft-versus-host disease after allogeneic bone marrow transplantation. At endoscopy 7 patients had characteristic desquamation of the upper esophagus; 2 of these also had distal esophagitis; and 3 had distinctive upper esophageal webs. No infectious pathogens were detected in esophageal biopsies or brushings. Abnormalities of esophageal motility were seen in 5 of 7 patients studied including 3 with aperistalsis. Retrosternal pain in 3 patients resulted from acid reflux. Esophageal histology from 5 autopsied patients showed no muscle or neuronal abnormalities by silver stain or conventional light microscopy. There was increased submucosal fibrosis associated with mucosal esophagitis and ulceration. Blind microscopic review of histology clearly distinguished the esophagus of chronic graft-versus-host disease from that of progressive systemic sclerosis. We conclude that esophageal epithelium, like skin and mucous membranes, is a target organ in chronic graft-versus-host disease. This immunologic disease results in desquamative esophagitis with web formation. Peptic esophagitis, a cause of severe pain and perhaps distal esophageal strictures in these patients, may be related to poor acid clearing from the esophagus. Diagnostic endoscopy and disruption of webs should be performed carefully to avoid perforation. Treatment should be directed toward suppressing the underlying immunologic disorder and at preventing acid-peptic reflux.
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PMID:Esophageal abnormalities in chronic graft-versus-host disease in humans. 700 15

Three patients who developed acute onset of cerebral blindness within 5-47 days of BMT using tacrolimus (FK506) as primary GVHD prophylaxis are described. This syndrome has been described with the use of cyclosporin A (CsA) and FK506 in solid organ transplant recipients. CsA-induced cerebral blindness has also been noted in BMT recipients but to date there have been no reports of this complication in BMT patients receiving FK506. We have noted a striking similarity in the clinical and radiographic presentations between these patients and those with CsA-associated cerebral blindness. Reversibility within 1-2 weeks of onset and the potential for substitution of CsA for FK506 in these patients is described.
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PMID:Tacrolimus (FK506)-induced cerebral blindness following bone marrow transplantation. 887 19

A 40-year-old woman underwent allogeneic peripheral blood stem cell transplantation for relapsed AML-M6. She developed graft-versus-host disease on day +15 post-transplant, for which she was treated with cyclosporin A and methyl prednisolone. On day +19 she developed cortical blindness, headache and convulsions which were associated with white matter changes on MRI scanning of the head and elevated cyclosporin A levels. A diagnosis of cyclosporin A encephalopathy was made and cyclosporin A was discontinued. Her vision recovered completely after 48 h and the other symptoms resolved. This is the first case of cyclosporin A encephalopathy to be reported in an allogeneic PBSC recipient.
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PMID:Reversible cortical blindness and convulsions with cyclosporin A toxicity in a patient undergoing allogeneic peripheral stem cell transplantation. 938 85

A 46-year-old woman with Hodgkin's disease who underwent nonmyeloablative allogeneic stem cell transplantation developed cortical blindness, seizures, and left hemiparesis on day 100 while receiving tacrolimus (FK506) and prednisone for the treatment of graft-versus-host disease (GVHD). Magnetic resonance imaging revealed multiple changes, mainly in the bilateral occipital lobes, suggesting FK506-related leukoencephalopathy. These abnormalities improved after discontinuation of FK506. However, 3 days after the episode, cerebral hemorrhage in the left occipital lobe with perforation to the left subdural space occurred. Although FK506-induced leukoencephalopathy with cerebral hemorrhage is considered the more severe form of such leukoencephalopathy, the patient's neurological symptoms almost completely resolved and radiographic findings improved after discontinuation of FK506, tapering of methylprednisolone, and initiation of mycophenolate mofetil. FK506-related leukoencephalopathy is a rare complication after allogeneic stem cell transplantation. Although the symptoms usually subside after discontinuation of FK506, therapeutic intervention in many cases may result in severe complications, including GVHD and vascular disease. We consider it important to use immunosuppressive agents without vascular endothelial toxicity for preventing the development of fatal GVHD after discontinuation of FK506.
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PMID:Successful treatment of tacrolimus (FK506)-related leukoencephalopathy with cerebral hemorrhage in a patient who underwent nonmyeloablative stem cell transplantation. 1554 Sep 7

Tacrolimus is a potent immunosuppressive drug widely used to prevent and treat graft-versus-host disease (GVHD) in stem cell transplantation (SCT). Among 49 patients receiving tacrolimus who underwent SCT from January 2000 to July 2003, 10 patients (20%) developed encephalopathy. The commonly observed symptoms were convulsions and drowsiness, and most patients complained of signal symptoms such as headache, nausea, and cortical blindness before onset. The most common abnormality on neuroimages was high-intensity lesions in white matter on magnetic resonance imaging T2-weighted or fluid-attenuated inversion recovery images. At onset, all patients were receiving treatment for acute GVHD (grade II/III) or extensive chronic GVHD and demonstrated an abrupt increase in blood pressure from baseline levels. The serum tacrolimus concentration was generally within acceptable levels at onset. Symptoms gradually improved in all patients when the blood pressure was lowered with antihypertensive medication, regardless of continued tacrolimus administration following a short-term suspension. The pathogenesis of tacrolimus-related encephalopathy is multifactorial, although refractory GVHD and a sudden increase in blood pressure seem to be major predisposing factors. Because the withdrawal of tacrolimus or switching to less potent anti-GVHD agents usually worsens the GVHD, the administration of tacrolimus should be managed by closely monitoring serum levels and controlling blood pressure.
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PMID:Tacrolimus-related encephalopathy following allogeneic stem cell transplantation in children. 1581 39

Metachromatic leukodystrophy (MLD) is an inherited demyelinating disease that causes progressive neurologic deterioration, leading to severe motor disability, developmental regression, seizures, blindness, deafness, and death. The disease presents as a late-infantile, juvenile, or adult form. Hematopoietic stem cell transplantation has been shown to slow disease progression. The purpose of this longitudinal study was to evaluate long-term treatment outcomes after unrelated donor umbilical cord blood (UCB) transplantation in pediatric patients according to disease burden and age at onset (ie, late-infantile versus juvenile). Engraftment, survival, treatment-related toxicity, graft-versus-host disease, neurophysiologic measures, and neurodevelopmental function were assessed. To evaluate whether signal intensity abnormalities on magnetic resonance imaging (ie, modified Loes scores) predict post-transplant cognitive and gross motor development, a general linear mixed model was fit to the data. Twenty-seven patients underwent transplantation after myeloablative chemotherapy; 24 patients engrafted after the initial transplantation. Seven patients died of infection, regimen-related toxicity, or disease progression. Twenty patients (6 with late-infantile onset and 14 with juvenile onset) were followed for a median of 5.1 years (range, 2.4 to 14.7). We found that patients with motor function symptoms at the time of transplant did not improve after transplantation. Brainstem auditory evoked responses, visual evoked potentials, electroencephalogram, and/or peripheral nerve conduction velocities stabilized or improved in juvenile patients but continued to worsen in most patients with the late-infantile presentation. Pretransplant modified Loes scores were highly correlated with developmental outcomes and predictive of cognitive and motor function. Children who were asymptomatic at the time of transplantation benefited most from the procedure. Children with juvenile onset and minimal symptoms showed stabilization or deterioration of motor skills but maintained cognitive skills. Overall, children with juvenile onset had better outcomes than those with late-infantile onset. As in other leukodystrophies, early intervention correlated with optimal outcomes. We conclude that UCB transplantation benefits children with presymptomatic late-infantile MLD or minimally symptomatic juvenile MLD.
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PMID:Neurodevelopmental outcomes of umbilical cord blood transplantation in metachromatic leukodystrophy. 2334 27

Autoimmune uveitis is an organ-specific disorder characterized by irreversible lesions to the eye that predominantly affect people in their most productive years and is among the leading causes of visual deficit and blindness. Currently available therapies are effective in the treatment of a wide spectrum of uveitis, but are often associated with severe side effects. Here, we review ongoing research with promising immunomodulatory therapeutic strategies, describing their specific features, interactions and the responses triggered by the targeted immune molecules that aim to minimize clinical complications and the likelihood of disease relapse. We first review the main features of the disease, diagnostic tools, and traditional forms of therapy, as well as the animal models predominantly used to understand the pathogenesis and test the novel intervention approaches aiming to control the acute immune and inflammatory responses and to dampen chronic responses. Both exploratory research and clinical trials have targeted either the blockade of effector pathways or of their companion co-stimulatory molecules. Examples of targets are T cell receptors (CD3), their co-stimulatory receptors (CD28, CTLA-4) and corresponding ligands (B7-1 and B7-2, also known as CD80 and CD86), and cytokines like IL-2 and their receptors. Here, we summarize the available evidence on effectiveness of these treatments in human and experimental uveitis and highlight a novel CD28 antagonist monovalent Fab' antibody, FR104, which has shown preclinical efficacy suppressing effector T cells while enhancing regulatory T cell function and immune tolerance in a humanized graft-versus-host disease (GVHD) mice model and is currently being tested in a mouse autoimmune uveitis model with encouraging results.
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PMID:Immunotherapeutic strategies in autoimmune uveitis. 2483 4

Ocular graft-versus-host disease (GvHD) is predominantly an inflammatory ocular surface disorder after allogeneic hematopoietic stem cell transplantation (HSCT) with increasing incidence. It is not only associated with reduced quality of life because of dry eye syndromes but can also impair visual acuity and lead to blindness due to corneal complications. The GvHD is mostly associated with severe moisturizing disorder of the ocular surface, which is often resistant to therapy and accompanied by chronic inflammation. Corneal complications are an important problem in these patients. An individually adapted multimodal stage-related and interdisciplinary therapy in cooperation with hematologists and oncologists is therefore important for the treatment of patients with ocular GvHD.
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PMID:[Ocular graft-versus-host disease]. 2660 95

Stem cells (SCs) are discovered long back but the idea that SCs possess therapeutic potential came up just a few decades back. In a past decade stem cell therapy is highly emerged and displayed tremendous potential for the treatment of a wide range of diseases and disorders such as blindness and vision impairment, type I diabetes, infertility, HIV, etc. SCs are very susceptible to destruction after transplantation into the host because of the inability to sustain elevated stress conditions inside the damaged tissue/organ. Heat shock proteins (HSPs) are molecular chaperones/stress proteins expressed in response to stress (elevated temperature, harmful chemicals, ischemia, viruses, etc) inside a living cell. HSPs protect the cell from damage by assisting in the proper folding of cellular proteins. This review briefly summarises different types of HSPs, their classification, cellular functions as well as the role of HSPs in regulating SC self-renewal and survival in the transplanted host. Applications of HSP modulated SCs in regenerative medicine and for the treatment of ischemic heart disease, myocardial infarction (MI), osteoarthritis, ischemic stroke, spinocerebellar ataxia type 3 (SCA3), leukemia, hepatic ischemia-reperfusion injury, Graft-versus-host disease (GVHD) and Parkinson's disease (PD) are discussed. In order to provide potential insights in understanding molecular mechanisms related to SCs in vertebrates, correlations between HSPs and SCs in cnidarians and planarians are also reviewed. There is a need to advance research in order to validate the use of HSPs for SC therapy and establish effective treatment strategies.
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PMID:Heat Shock Proteins and their Protective Roles in Stem Cell Biology. 3125 66

Background and Objectives: This research attempts to provide a clear view of the literature on randomized clinical trials (RCTs) concerning the efficacy of topical dexamethasone, clobetasol and budesonide in oral graft versus host disease (GVHD). Materials and Methods: An electronic search of the PubMed, Web of Science and Scopus databases was carried out for eligible RCTs. Studies were included if they had adult patients with oral GVHD treatment with topical corticosteroids, and if the RCT study was published in English. The Cochrane Risk of Bias tool was used to assess the quality of these studies. Overall, three RCTs were included (an Open, Randomized, Multicenter Trial; a Randomized Double-Blind Clinical Trial; and an Open-Label Phase II Randomized Trial). Results: The trials involved 76 patients, of which 44 patients received topical dexamethasone, 14 patients received topical clobetasol and 18 patients received topical budesonide. Topical agents were most frequently used when oral tissues were the sole site of involvement. It appears that the best overall response is present for budesonide with no difference between the four arms, followed by clobetasol, and then by dexamethasone. The limitation of the current study is mainly represented by the fact that overall response was derived in two of the studies from other parameters. Moreover, both budesonide and clobetasol were used in only one study each, while two assessed dexamethasone. Conclusions: Based on the clinical trials, all three agents seem to be effective in treating oral GVHD and had a satisfactory safety profile. There is still a need for assessing high quality RCTs to assess the efficacy of these therapies on a larger cohort.
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PMID:Topical Corticosteroids a Viable Solution for Oral Graft Versus Host Disease? A Systematic Insight on Randomized Clinical Trials. 3267 47


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