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)

Inbred strains of rats were used to analyze unidirectional host-versus-graft disease (transplant rejection) without graft-versus-host disease in small intestinal transplants and the immunosuppressive properties of cyclosporine (CsA). Forty-six Lewis rats received heterotopic transplants of the entire small bowel in four groups: Lewis-to-Lewis isografts, without CsA; Lewis-to-Lewis isografts, with CsA (15 mg/kg/day); (Lewis X ACI)F1-to-Lewis allografts, without CsA; (Lewis X ACI)F1-to-Lewis allografts, with CsA. Small bowel rejection was associated with gross morphological changes that preceded all other findings. A histologic scoring system assessed the degree of transplant rejection. A characteristic transient weight loss was seen in animals rejecting their bowels. Glucose absorption was impaired and polyethylene glycol absorption increased during rejection. Cyclosporine inhibited all of these changes in allografted rats. It is concluded that daily administration of cyclosporine is effective in preventing the morphologic and functional changes of acute transplant rejection in intestinal allografts and does not change these parameters in transplants that are not rejecting.
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PMID:Transplantation of the entire small bowel in inbred rats using cyclosporine. 357 68

Before 1972 several attempts were made to perform small intestinal transplantation in man for the treatment of diseases leading to major losses of the small intestine. No patient had survived for more than 76 days despite intensive conventional immunosuppressants. Small intestinal allotransplantation has been investigated, experimentally, since 1959. Lillehei initially reported the results of allotransplantation of various lengths of small intestine in the canine model. Surgical techniques for successful allogeneic small intestinal transplantation as well as the methods for graft preservation, were clarified. Autotransplants of the total small bowel in dogs survived indefinitely. However, in dogs receiving total small intestinal allotransplants the mean survival period was 8-15 days. Both rejection and graft-versus-host disease have been implicated in the short survival of experimental animals. With the advent of cyclosporine and its known action against both rejection and graft-versus-host disease, we studied the results of parenteral cyclosporine on the survival of dogs following total small intestinal allotransplantation. Cyclosporine greatly prolongs survival to a mean of 103 days, following transplantation of the small bowel, compared to only 12 days in dogs not receiving any immunosuppressive agent. Two of the treated dogs lived for longer than 200 days and one dog lived for more than 400 days. Following this, we have developed a method of histological monitoring of the allograft by making two exterior isolated pouches of the allograft, representing the histological events leading to rejection of the in-continuity bowel.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Experimental and clinical intestinal transplantation. 386 21

Cyclosporine is a potent new immunosuppressive agent utilized in clinical organ transplantation. Available evidence suggest that it interferes with the secretion of interleukin-2. However, the long term efficacy of cyclosporine in preventing allograft rejection may depend on a relative sparing of suppressor cells early in the allogeneic response, allowing them to mature and effect a state of operational tolerance. If this is the case, cyclosporine must not affect antigen priming or recognition. Two patients in our center underwent allogeneic spleen transplant in conjunction with renal and pancreatic transplant. Both patients were treated with therapeutic levels of cyclosporine during the course of transplant. Neither developed any clinical signs of renal or pancreatic transplant rejection. Both patients developed graft-versus-host disease and eventually required allogeneic (donor) splenectomy. Studies performed on the splenocytes recovered from these specimens demonstrate alloantigen-specific cytotoxic T cell precursors. These studies demonstrate that although cyclosporine can prevent allograft rejection it does not necessarily prevent or ameliorate graft-versus-host disease. Furthermore, cyclosporine does not prevent in vivo T cell priming of alloantigen recognition. The primed cytotoxic precursors can be expanded in the presence of exogenous interleukin-2 to become fully active cytoxic cells.
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PMID:Failure of cyclosporine to prevent in vivo T cell priming in man. Studies in allogeneic spleen transplantation. 389 94

Cyclosporin A has been used in conjunction with allogeneic bone-marrow transplantation in the treatment of 23 patients--21 with acute leukaemia, 1 with chronic granulocytic leukaemia, and 1 with aplastic anaemia. The drug was given twice daily from the day before transplant. At the start of the study cyclosporin prophylaxis was stopped in 3 patients within 44 days of transplantation because of non-specific rashes and/or deteriorating renal function. All 3 patients had acute graft-versus-host disease (GVHD) and died. Thereafter the drug was not stopped because of possible toxic manifestations, and 20 patients have been studied (median follow-up 7 months; maximum 13 months). 2 patients have acquired GVHD; 1 patient died of acute GVHD and 1 has chronic mild disease. 3 other patients have died, 2 of recurrent leukaemia and a third of staphylococcal pneumonia with renal failure. Of the remaining patients, 1 has recurrent leukaemia and 1 has moderately severe renal failure. Several toxic effects of cyclosporin A have been observed but they are mostly reversible and no second malignant neoplasm has developed.
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PMID:Cyclosporin A to prevent graft-versus-host disease in man after allogeneic bone-marrow transplantation. 610 87

There is a significant decrease in the ratio of inducer (helper) to suppressor T lymphocytes in the peripheral blood of patients with primary biliary cirrhosis (PBC). These changes are not seen in other forms of cholestatic liver disease, but are similar to those described in chronic graft-versus-host disease. Cyclosporin A treatment increased the proportion of suppressor A lymphocytes and improved liver function in 6 patients with PBC. This indicates that cyclosporin A is an immunoregulatory drug. Unfortunately nephrotoxicity precluded long-term use.
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PMID:Effects of cyclosporin A on suppressor and inducer T lymphocytes in primary biliary cirrhosis. 610 96

35 patients were treated for acute myeloid leukaemia or acute lymphoblastic leukaemia with allogeneic bone-marrow grafts from a parent, child, or sibling who was mismatched at the major histocompatibility complex (MHC). 11 of these patients are alive at least 6 months after grafting, 5 of them after more than 2 years. Of the 15 patients aged under 20 at the time of the graft, 8 are alive and well 6 months to 3 years later. Cyclosporin A was given to all patients after grafting. 1 patient died of acute graft-versus-host disease and in 2 other cases this was a major factor in their death. Graft failure caused the death of 2 patients. 4 patients died of recurrent leukaemia. A fatal complication in 12 patients was pulmonary oedema, often associated with convulsions, intravascular haemolysis, and renal failure. Some of these patients had viral or bacterial infections, but in the majority the syndrome was not associated with demonstrable infection. This syndrome, in which the essential lesion appears to be vascular, was much more common in recipients of mismatched than matched grafts. 3 others died from lung disease in which infection was a factor.
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PMID:Mismatched family donors for bone-marrow transplantation as treatment for acute leukaemia. 613

Immunologic recovery was studied in ten patients with aplastic anemia and 23 patients with hematologic malignancy who received HLA-identical marrow grafts and cyclosporine postgrafting as prophylaxis against graft-versus-host disease. Cyclosporine , 12.5 mg/kg/day, was administered beginning on the day before marrow infusion and continued for 50 days, when it was tapered and discontinued by 6 months postgrafting . Results were compared with data from concurrent and previously described patients receiving methotrexate as prophylaxis for graft-versus-host disease. Patients treated with cyclosporine or methotrexate had lower-than-normal immunologic parameters and were not different from one another 3-5 months postgrafting . By 11 to 18 months after grafting lymphocyte counts had normalized in both groups. Serum IgA levels were low and IgG levels had normalized in methotrexate-treated patients, and IgM was normal in cyclosporine -treated patients. In vivo antibody production to T-dependent antigens and skin test responses to recall antigens continued to be impaired. The response to the neoantigen dinitrochlorobenzene was still impaired in patients treated with cyclosporine and normal in patients given methotrexate. These data suggest that immunologic recovery after marrow transplantation is similar in cyclosporine -treated and methotrexate-treated patients.
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PMID:Immunologic recovery in human marrow graft recipients given cyclosporine or methotrexate for the prevention of graft-versus-host disease. 623 64

Cyclosporin A(CyA) is a valuable post graft immunosuppressive agent in allogeneic bone marrow transplantation. The use of CyA is associated with a reduction in severity of graft versus host disease and improved marrow engraftment. A major side effect of CyA is nephrotoxicity. In 33 patients studied during the first 4 weeks of therapy there is a close correlation between trough (12 h) serum cyclosporin A concentrations and plasma creatinine (r = 0.93, P less than 0.001) and urea (r = 0.88, P less than 0.001). Trough CyA serum concentrations of greater than 500 ng/ml are potentially nephrotoxic. Other risk factors for early nephrotoxicity in cyclosporin therapy are the concurrent use of aminoglycoside antibiotics (P = 0.01) and hyperbilirubinaemia (P = 0.01). Early nephrotoxicity can be prevented by maintaining trough CyA levels in the range 100-400 ng/ml. During prolonged CyA therapy, cumulative renal impairment can occur and nephrotoxic episodes associated with microangiopathic peripheral blood changes and hypertension are seen in a minority of patients.
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PMID:Nephrotoxicity in bone marrow transplant recipients treated with cyclosporin A. 634 56

Graft-versus-host disease (GVHD) was induced in Hooded (Rt1c) strain rats by means of high dose total body irradiation (TBI) and subsequent reconstitution with allogeneic bone marrow and spleen cells from WAG (Rt1u) strain donors. Untreated recipients of allogeneic cells died within 20 days of engraftment, whereas those treated daily with Cyclosporin A (CyA), given either from the day receipt of the graft (Day 0) or from Day 4, survived until the end of the experiment (Day 50). If delayed until Day 7, CyA prophylaxis was totally ineffective. Hooded rats bearing a syngeneic leukaemia were irradiated and reconstituted with allogeneic bone marrow. During the course of the ensuing graft-versus-host response (GVHR) leukaemia cells were eradicated from the spleens of the host animals. However, as a consequence of CyA prophylaxis, whether started on Day 0 or delayed until Day 4, the anti-leukaemia potential of the bone marrow allograft was completely abrogated. Anti-tumour activity after engraftment was detectable first at Day 7, i.e. the time at which the GVHR became intractable to the effects of CyA. The results indicate (1) that CyA suppresses the initial events but not the effector phase of the GVHR, and (2) that the anti-host and anti-tumour action of the GVHR may be temporally inseparable.
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PMID:Effect of cyclosporin A on the anti-leukaemia action associated with graft-versus-host disease. 634 98

Cyclosporin A (CyA) was used to minimize graft-versus-host disease (GVHD) in 28 recipients of allogeneic marrow transplants. When given orally, the absorption of CyA was markedly dependent on normal gut function. Patients without gut dysfunction showed normal serum concentration-time curves while those with diarrhoea from any cause (chemo-radiation enteritis, acute GVHD of the gut, infectious enteritis) showed minimal absorption of the drug. These data indicate the desirability of the intravenous administration of CyA during periods of gut dysfunction in marrow transplant recipients.
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PMID:Oral administration of cyclosporin A for recipients of allogeneic marrow transplants: implications of clinical gut dysfunction. 636 11


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