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)

Oral Cyclosporin A (CyA) was given for the prophylaxis of graft-versus-host disease (GVHD) to sixty-seven patients receiving a bone marrow transplant, and was found to be extremely effective in reducing the severity of acute GVHD. Side-effects of CyA included hypertrichosis, gum hypertrophy, and a rare but serious 'capillary leak' syndrome.
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PMID:Dermatological aspects of the use of Cyclosporin A for prophylaxis of graft-versus-host disease. 637 Feb 94

Immunologically mediated aplastic anemia (AA) in mice was induced by the i.v. injection of 10(7) lymph node cells (LNC) from H-2k identical but Mls mismatched CBA/J donor mice into previously irradiated (600 rad total body gamma) C3H/HeJ mice. Cyclosporin A (CsA), 25 mg/kg, was administered subcutaneously from day -1 to day 30. Control mice included C3H/HeJ mice which received 600 rad alone, C3H/HeJ mice which received 600 rad plus CsA as above, and C3H/HeJ mice which received 600 rad total body irradiation followed by 10(7) LNC from CBA/J donors. CsA failed to prevent lethal AA. These results suggest that the pathogenetic mechanisms operating in immunologically mediated AA differ from the mechanisms operating in rodents transplanted with allogeneically mismatched marrow or spleen cells which develop graft-versus-host disease. The results are consistent with a non-T cell-dependent mechanism causing the AA.
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PMID:Experimental immunologically mediated aplastic anemia (AA) in mice: cyclosporin A fails to protect against AA. 637 64

Cyclosporine, a cyclic endecapeptide of fungal origin, has recently been released for use in clinical transplantation. Trials in kidney, heart, liver and bone marrow recipients were encouraging: 1-year graft survival rates were 70% to 80% for kidney and heart recipients, and 60% to 65% for liver allograft recipients. Cyclosporine is also effective in treating bone marrow recipients with acute graft-versus-host disease. The drug selectively inhibits T-helper cell production of growth factors essential for B cell and cytotoxic T-cell differentiation and proliferation, while allowing expansion of suppressor T-cell populations. Drug absorption varies greatly, necessitating monitoring of drug level and individualization of therapy. Nephrotoxicity is the most frequent side effect of cyclosporine. An increased incidence of B-cell lymphomas seen when cyclosporine was used in conjunction with cytotoxic agents or anti-lymphocyte globulin has very rarely been observed when concomitant immunosuppression has been limited to low-dose corticosteroids. Lower initial doses of cyclosporine, followed by more rapid tapering may reduce the incidence of nephrotoxicity without compromising improved graft outcome.
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PMID:Cyclosporine: a new immunosuppressive agent for organ transplantation. 638 99

Twenty-four patients have received bone marrow transplantation for severe aplastic anaemia at the Westminster Hospitals since 1974. Twelve patients are long term survivors. Infectious complications in association with graft rejection, graft versus host disease or prolonged neutropenia were the major cause of death. In the last 18 months the introduction of more effective conditioning regimes and Cyclosporin A as graft versus host disease prophylaxis has improved the survival rate to 85%. One patient has required regrafting for late graft failure without evidence of graft rejection.
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PMID:Bone marrow transplantation for severe aplastic anaemia. A review of the Westminster experience of 24 cases. 641 17

A series of fractionated partial irradiations which consisted of either 3 gray x 6 times or 3 gray x 4 times, combined with pharmacological immunosuppression (Cyclosporin A: Cs-A) ensure a SLA semidifferent bone marrow graft in the pig. Bone marrow and peripheral blood lymphocytes chimerism was readily detectable. No graft versus host disease (GVHD) symptoms were noticed as long as Cs-A was given at a sufficient dose. However when Cs-A treatment was stopped GVHD or rejection of the graft developed rapidly.
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PMID:[Incompatible SLA bone marrow graft in swine after fractional irradiation and administration of cyclosporin A]. 680 May 74

Oral cyclosporin A was used as prophylaxis against graft-versus-host disease in (a) 31 patients with acute leukaemia or aplastic anaemia given transplants of HLA-matched bone marrow and (b) five patients with inborn errors of metabolism given transplants of haplotype-identical (parental) bone marrow. Twenty-six patients survived longer than two months after the operation. Despite the cyclosporin A, 31 patients (86%) suffered an acute form of graft-versus-host disease and 22 (61%) a chronic form. Nevertheless, the disease was usually treatable with immunosuppressive agents and caused the death of only one patient. Cyclosporin A caused renal toxicity in all cases; occasionally this was associated with a "capillary leak" syndrome, fatal in two patients. In children hypertension, fits, and fluid retention were common side effects. Blood concentrations of cyclosporin A correlated with blood urea values and blood pressure but did not predict the occurrence of graft-versus-host disease. Four different dose schedules were used to find the optimum way to administer this drug. Oral cyclosporin A is extremely effective at reducing the severity of graft-versus-host disease, but prevention of the disease is limited by toxicity of the drug and variable absorption. Better results might be achieved with parenteral administration or by using the drug in combination with other methods.
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PMID:Cyclosporin A as prophylaxis against graft-versus-host disease in 36 patients. 680 91

We present the preliminary results of bone marrow transplantation for severe aplastic anaemia using the new immunosuppressive drug Cyclosporin A. We have compared the first seven patients treated with Cyclosporin A as post-graft immunosuppression with 14 similar patients with severe aplastic anaemia transplanted using methotrexate as the immunosuppressive drug in the post-graft period. All seven of our patients treated with Cyclosporin A have engrafted and so far there have been no rejection episodes, although the follow up period is short (greater than 94 to greater than 209 d). These results compare favourably with the methotrexate group of patients in whom five of the 15 patients either failed to engraft or subsequently rejected the graft. We have not encountered irreversible renal or hepatic failure due to Cyclosporin A and so far other effects such as hirsutism and mental changes have not been clinically significant. Two out of the seven patients treated with Cyclosporin A developed severe graft-versus-host disease (Grade III--IV). Four of the nine patients at risk in the methotrexate group developed severe (Grade III--IV) graft-versus-host disease.
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PMID:Immunosuppression with cyclosporin A in allogeneic bone marrow transplantation for severe aplastic anaemia: preliminary studies. 701 66

The advances in chemotherapy, understanding of leukaemia cell biology and supportive care for acute leukaemia patients offer substantial prospect for cure in the future. Intensive treatment of acute leukaemia requires the resources of specialised unites for support of bone marrow failure. Where possible, patients should be referred to such units for diagnostic classification and intensive remission induction therapy. The understanding of leukaemia cell biology and the detection of colony stimulating activity in normal granulocytes and marrow has helped in predicting early relapses in leukaemia patients. Allogeneic sibling bone marrow transplantation for patients in remission offers a 70% chance of 3 years survival and disease-free state compared to 10% survival for the non-grafted patients treated on maintenance chemotherapy alone. Current evidence suggests that such transplanted patients do not require long term chemotherapy or anti-G.V.H. treated now that the problem of graft-versus-host disease in transplant recipients appears to be overcome by the use of Cyclosporin A.
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PMID:New concepts on the acute leukaemias: morphology, classification, cell biology, chemotherapy, supportive care, immunotherapy and bone marrow transplantation. 703 35

Cyclosporin A (Cy A; 15 mg/kg s.c.) allows allogeneic histoincompatible skin graft survival in 10 of 10 rabbits as long as the drug is given. The same dose of Cy A does not affect acute graft-versus-host disease (GVHD) and increase survival of rabbits after allogeneic bone marrow transplantation between the same two strains, when two groups of 15 animals are tested. Median survival of 14 engrafted animals without Cy A was 23 days, of 12 engrafted animals with Cy A 22 days (not significant). Cryopreservation of bone marrow delays the onset of GVHD and increases survival of engrafted animals. Median survival of 5 engrafted animals without Cy A was 33 days, of 14 engrafted animals with Cy A 35 days. Our hypothesis is that one part of early GVHD as well as of early graft rejection is mediated by a subclass of cells which is resistant to Cy A. This hypothesis is supported by the finding that most transplanted skins show a self-limited period of infiltration and induration. Skin grafts survive this period of infiltration. If the same potentially self-limited process occurs in the liver or the intestine during acute GVHD, animals die. this hypothesis could explain why Cy A allows skin graft survival but does not affect acute GVHD.
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PMID:Histoincompatible skin and marrow grafts in rabbits on cyclosporin A. 704 61

The treatment of rheumatoid arthritis and psoriatic arthritis with cyclosporin A is described. Cyslosporin A is a new selective immunosuppressant which acts primarily on the T lymphocytes. It has already been shown to be effective in preventing rejection following kidney transplantation as well as in preventing graft-versus-host disease. In rheumatoid and psoriatic arthritis, however, its effect was not satisfactory, although rather different in the two conditions; overall only about one third of the patients showed any marked improvement. By contrast, and for reasons which are as yet unexplained, it had a beneficial effect on the cutaneous symptoms of psoriasis. Cyclosporin A had little effect on immune parameters. Side effects--mainly kidney toxicity, gastro-intestinal reactions and hirsutism--were common but reversible. On present evidence its principal indication among rheumatological diseases would seem to be as a treatment for severe, intractable psoriatic arthritis.
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PMID:[Cyclosporin A--effects and side effects in the treatment of rheumatoid and psoriatic arthritis (author's transl)]. 723 53


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