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)

In mice, as in humans, lethal graft-versus-host disease (GVHD) with skin involvement often occurs in immunoincompetent recipients of donor hematopoietic cells in spite of matching at major histocompatibility loci and nonreactivity in mixed lymphocyte culture, if donor and recipient are disparate at several minor histocompatibility loci. In mice, both death and skin disease can be prevented by the use of an antiserum containing antibodies to a cell surface glycolipid, asialo GM1 (ASGM1). Because treatment of only the recipients with anti-asialo GM1 substantially reduces the subsequent proliferation of infused donor lymphoid cells, we infer that anti-asialo GM1 interferes with a host minor-antigen-presenting cell, so that donor lymphocytes fail to see minor host antigens as immunogenic. Of the tissues examined by immunofluorescence microscopy, ASGM1 was found on the epidermal Thy-1+ dendritic cell, on dendritic cells in the thymus, and as has been previously described, on lung and spleen cells. Following the intravenous administration of anti-asialo GM1, only the spleen showed an obvious change, losing approximately 80% of its ASGM1 + cells. Further analysis of spleen cells bearing ASGM1 may better define the phenotype of the inferred minor antigen-presenting cell and lead to a method of improving the outcome of human bone marrow transplantation.
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PMID:Studies addressing the mechanism of anti-asialo GM1 prevention of graft-versus-host disease due to minor histocompatibility antigenic differences. 400 80

Human graft-versus-host disease (GVHD) has several cutaneous manifestations, including a lichenoid and a sclerotic injury pattern. A versatile animal model of graft-versus-host skin disease (GVHSD) would facilitate study of the pathophysiology of these two cutaneous injury patterns. We have examined two murine chimeras histologically and have found two distinct patterns. Allogeneically transplanted B1/6 mice show a prolonged lichenoid-interface dermatitis that eventuates in clinical alopecia, whereas LP/J recipients of allogeneic cells do not show hair loss. Their histopathology consists of an early lichenoid phase that abates and is replaced by dermal sclerosis. Because of the versatility of the mouse as a laboratory animal, we feel that this model provides an excellent opportunity to define the immunopathologic mechanisms responsible for skin injury in GVHD. In addition, an understanding of the pathogenesis of the T cell-dependent, lichenoid, and sclerotic patterns of tissue injury in GVHSD might well provide insight into the pathogenesis of the GVHSD analogs, cutaneous lupus erythematosus and scleroderma.
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PMID:Murine graft-versus-host skin disease: a chronologic and quantitative analysis of two histologic patterns. 663 Oct 52

The expression of CD34 and endothelial leucocyte adhesion molecule-1 (ELAM-1) on endothelial cells was studied in skin biopsies from normal human donors and recipients of allogeneic bone marrow. Both molecules were demonstrable on a variable number of cells in normals with no significant change after marrow transplantation in patients with no clinical evidence of skin disease. In patients with graft-versus-host disease (GvHD), however, there was a striking decrease in CD34-positive cells with a corresponding increase in ELAM-1 positivity. These changes were similar to those occurring in cultured endothelial cells after the addition of certain cytokines. They were seen only in the presence of a lymphocytic infiltrate and were not observed in the early stages of GvHD before lymphocytic infiltration was discernible. The reciprocal expression of these molecules may thus be important in the adhesion of lymphocytes to endothelium and their entry into the skin in GvHD and may be modulated by local cytokine release.
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PMID:Reciprocal expression of CD34 and cell adhesion molecule ELAM-1 on vascular endothelium in acute cutaneous graft-versus-host disease. 768 20

Seventy-one patients with moderate to severe acute GVHD after BMT were analysed retrospectively. At the start of therapy 96% of the patients had rashes, 45% liver abnormalities and 54% gut dysfunctions. Forty-four patients (62%) had been treated for grade I GVHD with systemic corticosteroids. First therapy for moderate to severe acute GVHD was with corticosteroids (n = 59), psoralen with ultraviolet light (PUVA) (n = 14), cyclosporin (CsA) (n = 10), antithymocyte globulin (ATG) (n = 7), methotrexate (MTX) (n = 2), monoclonal antibodies (n = 1) or thalidomide (n = 1). In 18 of these patients two or more agents were combined. Resolution of skin disease and evaluable liver and gut disease were seen in 48%, 44% and 47% of cases, respectively. Overall complete resolution was seen in 37%. Thirty-two patients received a second treatment, resulting in complete resolution in 31%. Patients with a complete response had an actuarial transplant-related mortality of 37% compared with 82% or worse for patients with other outcomes (p < or = 0.003). Combined treatment was superior to ATG, but not better than corticosteroids. In multivariate analysis a low total sum severity score was the only factor associated with complete response (p = 0.02). AML diagnosis (p = 0.01) and GVHD of the liver (p = 0.02) were independent risk factors for treatment failure.
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PMID:Treatment of moderate to severe acute graft-versus-host disease: a retrospective analysis. 785 35

Histiocytic cytophagic panniculitis (HCP) is the name given to the hemophagocytic syndrome when subcutaneous fat is involved. Histologically, it is characterized by phagocytosis of blood elements by histiocytes that appear to be benign. We report this rare skin disease in a 46-year-old patient that occurred 32 months after an allogeneic bone marrow transplantation. This skin disease could be a manifestation of graft-versus-host disease, although the connection remains speculative.
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PMID:Histiocytic cytophagic panniculitis: a rare late complication of allogeneic bone marrow transplantation. 785 41

Humanized anti-Tac is a genetically engineered human IgG1 monoclonal antibody specific for Tac, the alpha subunit of the interleukin-2 (IL-2) receptor, and blocks IL-2-dependent activation of human T lymphocytes. The safety, pharmacokinetics, and immunosuppressive activity of humanized anti-Tac were evaluated in 20 patients who developed acute graft-versus-host disease (GVHD) after allogeneic marrow transplantation. Patients had developed acute GVHD at 5 to 26 (median, 14) days after transplantation and had failed to respond to primary therapy with glucocorticoids. Sequential groups of 4 patients each received a single 1-hour infusion of antibody in escalating doses of 0.5, 1.0, or 1.5 mg/kg; 8 additional patients were then treated with 1.5 mg/kg. A second infusion of antibody was administered after 11 to 48 (median, 16) days in 8 patients who had transient improvement of GVHD after the first infusion. Acute side effects, limited to chills in 1 patient and diaphoresis in another, were observed during or shortly after the antibody infusion. Overall improvement of acute GVHD occurred in 8 patients, 6 of whom were treated with a single antibody infusion and 2 with two infusions. Four responses were complete and 4 were partial. Three additional patients had improvement in one organ but progression in another. Responses occurred in 9 of 16 cases with skin disease, 3 of 15 with liver disease, and 6 of 12 with gastrointestinal disease. Two patients survive at 529 and 645 days after antibody treatment. Two patients died after relapse of leukemia. Sixteen patients died of infection or organ failure between 5 and 211 (median, 55) days. The terminal elimination half-life of the antibody was 44 to 363 hours, with a harmonic mean of 79, 88, and 94 hours, respectively, for the three doses studied. Absolute peripheral blood T-lymphocyte counts remained unchanged during the 56 days after infusion of the antibody. A fraction of circulating T cells expressed the alpha chain of the IL-2 receptor that, in some patients, was bound by antibody in vivo up to 28 days after treatment. No patient developed a measurable antibody response to humanized anti-Tac. Humanized anti-Tac has a long half-life after intravenous injection in humans, superior to any rodent monoclonal antibody specific for human T cells, and does not appear to induce antibody formation in recipients of marrow transplants. Improvement of steroid-refractory GVHD in 40% of patients after only one or two antibody infusions indicates that humanized anti-Tac is immunosuppressive.
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PMID:Treatment of acute graft-versus-host disease with humanized anti-Tac: an antibody that binds to the interleukin-2 receptor. 804 47

Living-related donor liver transplantation (LDLT) is an accepted approach to pediatric liver transplantation. Parental donation imposes a significant risk of chimerism with graft-versus-host disease (GVHD) because donors homozygous at all HLA loci (1.6% of the population) present no mismatched HLA antigens to be recognized by their offspring's immune system. The case of a 9-month-old who underwent LDLT with her 23-year-old HLA-homozygous mother as a donor demonstrates the consequences of this occurrence. The patient developed GVHD with aplastic anemia; the patient's nucleated peripheral blood elements were shown to be entirely derived from the donor. Later, after some marrow recovery, the patient's circulating lymphocytes had a donor origin, while the marrow-derived neutrophils had a recipient origin. The patient suffers from chronic GVHD and debilitating skin disease several years posttransplant. Our current protocol calls for HLA typing to eliminate parents who are homozygous at all HLA loci as donors of hepatic allografts to their children.
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PMID:Complete lymphoid chimerism and chronic graft-versus-host disease in an infant recipient of a hepatic allograft from an HLA-homozygous parental living donor. 895 84

Toxic epidermal necrolysis (TEN) is a severe blistering skin disease of high mortality. TEN may occur after bone marrow transplantation (BMT). In such cases, TEN have been attributed to graft-versus-host disease (GVHD) or an adverse drug reaction. It is very difficult to distinguish the causes of TEN after BMT. We report a 21-year-old Japanese man who developed TEN eight days after BMT, evaluate the differential diagnosis of hyperacute GVHD and an adverse drug reaction, and deduce that hyperacute GVHD was the more likely pathogenesis of TEN in this patient.
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PMID:Toxic epidermal necrolysis possibly linked to hyperacute graft-versus-host disease after allogeneic bone marrow transplantation. 937 62

We reviewed the records and reevaluated 212 patients with aplastic anemia transplanted at the Fred Hutchinson Cancer Research Center (FHCRC) between 1970 and 1993 who survived >/=2 years and who have been followed for up to 26 years. Parameters analyzed included hematopoietic function, chronic graft-versus-host disease (GVHD), skin disease, cataracts, lung disease, skeletal problems, posttransplant malignancy, depression, pregnancy/fatherhood, and the return to work or school, as well as patient self-assessment of physical and psychosocial health, social interactions, memory and concentration, and overall severity of symptoms. Survival probabilities at 20 years were 89% for patients without (n = 125) and 69% for patients with chronic GVHD (n = 86) (the status was uncertain in 1 surviving patient). All patients had normal hematopoietic parameters. Skin problems occurred in 14%, cataracts in 12%, lung disease in 24%, and bone and joint problems in 18% of patients. Eleven patients (12%) developed a solid tumor malignancy and 19% of patients experienced depression. Chronic GVHD was the dominant risk factor for late complications. Seventeen patients died at 2.5 to 20.4 years posttransplant; 13 of these had chronic GVHD and related complications. At 2 years, 83% of patients had returned to school or work; the proportion increased to 90% by 20 years. At least half of the patients preserved or regained the ability to become pregnant or father children. Patients rated their quality of life as excellent and symptoms as minimal or mild. In conclusion, marrow transplantation in patients with aplastic anemia established long-term normal hematopoiesis. No new hematologic disorders occurred. The major cause of morbidity and mortality was chronic GVHD. However, the majority of patients who survived beyond 2 years returned to a fully functional life.
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PMID:Long-term outcome after marrow transplantation for severe aplastic anemia. 957 99

Graft-versus-host disease (GVHD) in both its acute and chronic forms is a severe complication after allogeneic marrow transplantation. GVHD is associated with structural and functional defects in many organs and tissues. Severe immunoincompetence may result in frequent, often severe and at times fatal infections caused by various organisms. Prolonged antibiotic prophylaxis, and possibly immunoglobulin administration are beneficial. Ocular complications, airway and pulmonary damage, and oral or dental problems may cause severe morbidity. Despite aggressive management, a proportion of patients will succumb to these complications. Severe skin disease and joint contractures are currently seen less frequently, mostly due to early treatment of the disease. Psychosocial rehabilitation of patients with chronic GVHD is a demanding and protracted challenge and should be approached by a multidisciplinary team.
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PMID:Graft-versus-host disease and the development of late complications. 1015 45


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