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)

Acute graft-versus-host disease (GVHD), a major complication of allogeneic bone marrow transplantation (BMT), is probably mediated by T lymphocytes present in the marrow graft. In this study, the repopulation of the peripheral blood with T4+ and T8+ T cells was investigated during the period preceding the occurrence of acute GVHD. Twenty-four allogeneic and 11 autologous BMT recipients were monitored from day 4 post-BMT onward by the use of monoclonal antibodies, indirect immunofluorescence, and flow cytometry. The recipients of allogeneic transplants received methotrexate as GVHD prophylaxis. Similar recovery patterns for T4+ and T8+ T cells were found following autologous and allogeneic BMT. However, lymphoid repopulation occurred at a clearly faster rate after autologous BMT. T4+ T cells were the first to reappear in the peripheral blood, followed by T8+ T cells 4-7 days later. The T8+ T cell reconstitution occurred at an even faster rate in patients who were to develop grade II-IV GVHD, as compared with those with grade O-I GVHD, thus leading to an earlier decrease in the T4/T8 ratio. Of 10 patients with a T4/T8 ratio less than 2.5 at day 19, 9 developed grade II-IV GVHD and 1 showed no GVHD. Of 14 patients with a ratio greater than 2.5 at that time, only 2 developed grade II-IV and 12 grade O-I GVHD (p less than 0.001). In the 11 patients developing grade II-IV GVHD, the T4/T8 ratio decreased to values less than 2.5 before the first clinical symptoms of GVHD in 9; it coincided in one and occurred later in another patient. Thus, early monitoring of the T4/T8 ratio can distinguish patients at risk of developing grade II-IV GVHD.
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PMID:T lymphocyte repopulation and differentiation after bone marrow transplantation. Early shifts in the ratio between T4+ and T8+ T lymphocytes correlate with the occurrence of acute graft-versus-host disease. 637 96

Twenty-one patients, 18 with leukemia and three with severe aplastic anemia, were treated by allogeneic bone marrow transplantation. Acute graft-versus-host disease (GVHD) developed in 13 patients (62%), of whom nine (69%) had grade I, two grade II, one grade III and one grade IV. In all nine patients with grade I, elevation of the serum glutamic pyruvic transaminase level without an increase in the serum bilirubin level was observed, which suggested the presence of GVHD in the liver. All 11 patients with grade I and II responded well to therapy with predonisolone. Eleven (73%) of the 15 patients who survived for more than 100 days after marrow transplantation developed chronic GVHD. As signs of chronic GVHD, hepatic disturbances were observed in nine patients (82%), while exanthema, ophthalmic symptoms and oral mucosal symptoms were observed in seven (64%), six (55%) and four (36%), respectively. These symptoms could be well controlled by predonisolone combined with either azathioprine or cyclosporin A. Of the five deaths following the onset of chronic GVHD, three were due to interstitial pneumonitis, one to sepsis and one to relapse of the leukemia. Karnofsky's performance scores of five of the six surviving patients with chronic GVHD were 90%. Six patients with acute leukemia were still alive more than six months after marrow grafting. None of them have shown recurrence of leukemia. Five of these six had chronic GVHD.
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PMID:Graft-versus-host disease following allogeneic bone marrow transplantation. 639 14

Acute graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation is the most significant limiting factor preventing the widespread application of transplant therapy in acute leukemia and aplastic anemia. GVHD is mediated by T cells that contaminate harvested marrow in proportions ranging from 5-50% of the mononuclear cell population. T cell depletion (TCD) of large volumes of human marrow by E-rosetting for 24 h at 4 degrees C with modified sheep erythrocytes achieves removal of greater than or equal to 97% of all T cells, as judged by cytofluorographic analysis of the T-depleted bone marrow population with a broad panel of anti-T cell monoclonal antibodies, and abrogates functional T cell activity. Although T-depleted bone marrow cell recoveries were 2 logs below total harvested buffy coat cell numbers, the TCD mononuclear population was more than 99% viable and was enriched twofold for Ia+ cells as judged by cytofluorographic analysis. This method is at least the equivalent of those employing lectin column or monoclonal antibody/complement lysis techniques and is simpler to perform. Successful engraftment of adult patients can safely be obtained with as few as 4 X 10(8) total mononuclear cells following the 24-h procedure suggesting that prolonged or repeated T-depletion procedures do not interfere with stem cell engraftment. Preliminary results suggest that this method of TCD may ameliorate GVHD in histoincompatible transplants.
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PMID:An improved method for T-cell depletion of allogeneic histoincompatible donor bone marrow. 639 56

One hundred one patients with severe aplastic anemia underwent allogeneic marrow transplantation and received one of three forms of infection prophylaxis: oral nonabsorbable antibiotics and isolation and decontamination in a laminar airflow room (36 patients); prophylactic granulocyte transfusions from a single family member donor (33 patients); or conventional treatment in single rooms with hand-washing and mask precautions (31 patients). During the period of granulocytopenia, patients in the laminar airflow rooms acquired fewer infections than either of the other groups, but this difference was statistically significant only when compared with the group receiving conventional treatment. Patients in the laminar airflow rooms had significantly fewer infections after engraftment as compared with the other two groups. Incidence of interstitial pneumonia and graft rejection was not different among the three groups. Acute graft-versus-host disease occurred later (Day 47) in the group in the laminar airflow rooms as compared with the group receiving prophylactic granulocyte transfusions (Day 23) or the group receiving conventional treatment (Day 20). The incidence of grades II to IV acute graft-versus-host disease was less in the patients in the laminar airflow rooms but only reached borderline significance (p = 0.08) when compared with the conventionally treated patients. The survival at Day 100 was 92 percent for the group in the laminar airflow rooms, 79 percent for the group receiving prophylactic granulocyte transfusions, and 64 percent for the group receiving conventional treatment.
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PMID:Prophylaxis of infection in patients with aplastic anemia receiving allogeneic marrow transplants. 642 64

Transfusion of blood products containing immunocompetent lymphocytes may cause graft-versus-host disease (GVHD) in immunosuppressed recipients. We describe fatal GVHD which occurred in a 30-year-old renal transplant patient 2 weeks after transfusion of 1.0 x 10(8) lymphocytes/kilogram. In addition to typical cutaneous and gastrointestinal manifestations, she developed irreversible bone marrow failure. Acute GVHD following blood product transfusion from normal donors has a mortality of 88%. Treatment is unsatisfactory, but irradiation of blood products prior to administration is preventive.
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PMID:Graft-versus-host disease from leukocyte transfusions. 663 Jun 3

Human graft versus host disease is composed of 2 distinct clinical entities, acute graft versus host disease and chronic graft versus host disease, which have different pathogenesis. Acute graft versus host disease is produced by the attack of donor immunocompetent T or null lymphocytes against recipient histocompatibility antigens. The null lymphocytes may attack antigens shared by the donor and recipient and are autocytotoxic lymphocytes which can produce acute graft versus host disease in recipients of identical twin transplants. The cessation of acute graft versus host disease occurs when suppressor lymphocytes appear in the recipient's peripheral circulation. Chronic graft versus host disease is produced by immunocompetent lymphocytes that differentiate in the recipient. Its control is unknown. Some patients with chronic graft versus host disease have in vivo activated suppressor lymphocytes which produce a secondary immunoincompetence and an increased susceptibility to bacterial sepsis and death.
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PMID:Human graft versus host disease. 699 70

We have previously reported the protective effect of pretreatment of semiallogeneic marrow and spleen cells with Fab fragments of horse anti-mouse thymocyte globulin against otherwise 100% fatal acute graft-versus-host disease (GVHD). We have now examined the effect of this pretreatment in three allogeneic strain combinations of mice, namely, A leads to C57, CBA leads to CAF1, and CBA leads to BALB/c. Acute GVHD mortality at 15 days postirradiation and transplantation of untreated marrow and spleen cells was 100% in all the strain combinations. However, pretreatment of cells with Fab reduced acute GVHD mortality to 6, 13, and 33% for the CBA leads to CAF1, CBA leads to BALB/c, and A leads to C57 strain combinations, respectively. The combined mortality from both acute and secondary GVHD and all other causes at 60 and 200 days postirradiation was 6 and 11%, 20 and 39%, 50 and 66% for each of these strain combinations, respectively. These results provide additional evidence for the effectiveness of Fab in ameliorating acute GVHD and establish its applicability to allogeneic strain combinations.
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PMID:Amelioration of graft-versus-host disease by pretreatment of allogeneic cells with Fab fragments. 701 3

Acute graft-versus-host disease is a major problem in allogeneic bone-marrow transplantation. We performed a randomized study to compare the effectiveness of two regimens in the prevention of acute graft-versus-host disease. Thirty-five patients received methotrexate alone, and 32 received methotrexate, antithymocyte globulin, and prednisone. Of the patients who received methotrexate alone, 48 per cent had acute graft-versus-host disease, as compared with 21 per cent of those who received methotrexate, antithymocyte globulin, and prednisone (P = 0.01). The age of the recipient was a significant factor in the development of acute graft-versus-host disease: Older patients had a higher incidence of the disease (P = 0.001). We conclude that the combination of methotrexate, antithymocyte globulin, and prednisone significantly decreased the incidence of acute graft-versus-host disease and should be used to prevent this disorder in patients receiving allogeneic marrow transplants.
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PMID:A randomized study of the prevention of acute graft-versus-host disease. 703 50

Procedures for total and selective gastrointestinal decontamination of dogs are described. The selective procedure removed only Gram negative aerobic bacteria, yeast and fungi. Dogs receiving total decontamination were less susceptible to the GI syndrome following total body irradiation (TBI) than dogs receiving conventional care. After TBI and allogeneic bone marrow transplantation, serum albumin levels decreased in conventional animals, but remained normal in totally or selectively decontaminated animals. Exogenous infections occurred frequently in both irradiated, and totally decontaminated animals, but were absent in selectively decontaminated animals. Endogenous infections after total body irradiation were prevented only by total decontamination. Endogenous infections occurred in selectively decontaminated animals, but with milder clinical symptoms than in conventional animals. Appearance of donor type leukocytes and serum gamma globulin was slower in decontaminated animals than in conventionally treated controls. Acute graft versus host disease caused by a limited number of lymphocytes of a DLA identical littermate donor were prevented by selective gastrointestinal decontamination. Complications due to late immune reconstitution obscured the effect of decontamination on delayed graft versus host disease.
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PMID:Gastrointestinal decontamination of dogs treated with total body irradiation and bone marrow transplantation. 704 95

We have previously reported that xenogeneic lethal acute graft-versus-host disease (GVHD) was induced by transplantation of a mixture of human IL-2 activated natural killer (NK) and T cells into SCID mice conditioned with 4 Gy total-body irradiation (TBI), but not by IL-2-activated pure human T cells or NK cells. TBI and transplantation of the mixture of activated cells were both required to produce the lethal effect. We now report the effect of human IL-2 activated NK, T, or NK+T effector cells on the development of acute and chronic GVHD and GVL in SCID mice bearing human leukemic cells. Ten days after being inoculated i.v. with 2 x 10(7) human U-937 or K-562 leukemic cells, SCID mice, hereafter termed hu-leukemic mice, were radiated with 4 Gy TBI and transplanted i.v. with 5 x 10(7) human IL-2-activated NK, T, or NK+T effector cells. Hu-leukemic control mice received neither TBI nor effector cell transplantation. Acute GVHD-positive control SCID mice were transplanted with 5 x 10(7) H-2-incompatible C57Bl/6 splenocytes following 4 Gy TBI. The mice were observed for signs of GVHD and leukemia for 90 days. Twenty of 20 non-effector cell-transplanted control hu-leukemic mice developed signs related to leukemia and died with leukemic infiltration in the brain, liver, kidney, and lung 50-65 days after inoculation. Flow cytometry (FC) demonstrated 21-89% human leukemic cell infiltration in the bone marrow. Fourteen of 14 hu-leukemic mice transplanted with NK+T effector cells did not develop signs of advanced leukemia but died within 17 days of acute GVHD. FC demonstrated no human leukemic cells in their marrow. Twelve of 15 and 18 of 25 hu-leukemic mice transplanted with either NK or T cells survived 90 days without any evidence of symptomatic leukemia (P < 0.01 compared with non-effector cell-transplanted groups). NK-transplanted hu-leukemic animals experienced mild-to-moderate acute GVHD during the first 10-20 days posttransplantation, but gradually recovered and did not develop chronic GVHD. Hu-leukemic animals transplanted with T effector cells manifested no signs of leukemia or acute GVHD but chronic GVHD skin lesions appeared 80-90 days after transplantation. We conclude that acute GVHD, chronic GVHD, and GVL are associated but separable phenomena.
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PMID:The effect of human IL-2-activated natural killer and T cells on graft-versus-host disease and graft-versus-leukemia in SCID mice bearing human leukemic cells. 748 42


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