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)

Sequential changes in serum erythropoietin (sEPO) levels were measured by radioimmunoassay in six patients receiving autologous rescue (AR) and 11 patients receiving an allogeneic bone marrow transplant (BMT) for malignant disease. Longitudinal studies showed an inverse relationship between sEPO and haemoglobin levels in the autologous rescue and allogeneic transplant patients throughout the 130 d post-transplant study period. Early post-conditioning EPO responses were normal for the haemoglobin level in both groups, but after day 14 post-transplant, erythropoietin production in response to anaemia became impaired in one autologous rescue patient and eight of the 11 allogeneic transplant patients. There was no clear association between late impairment of sEPO production and conditioning therapy, infection, graft-versus-host disease, immunosuppressive therapy or serum creatinine. Blood transfusion requirements were similar for both groups in the first month after transplantation, but from days 31 to 90 post-transplant, BMT patients required an average of 5.5 units per patient compared with 1 unit per patient for the autologous group. Marrow transplant procedures do not affect early EPO responses but may diminish late responses. The potential value of exogenous rHuEPO in hastening engraftment and decreasing transfusion requirements, particularly for those patients who appear to have impaired EPO responses, remains to be shown by clinical trials.
Br J Haematol 1990 Sep
PMID:Serum erythropoietin changes in autologous and allogeneic bone marrow transplant patients. 222 32

Graft-versus-leukemia (GVL) is a major component of the overall beneficial effects of allogeneic bone marrow transplantation (BMT) in the treatment of leukemia. Although several clinical trials have suggested a direct relationship between GVL effects and acute and chronic graft-versus-host disease (GVHD), it is not yet known whether GVL can be separated from GVHD. However, several investigations in murine models of human leukemia indicate that the two may be at least partially separable. Moreover, analysis of clinical data from the International Bone Marrow Transplant Registry suggest that allogeneic BMT may be more advantageous than syngeneic BMT, regardless of the GVHD. Likewise, T lymphocyte depletion is associated with an increased incidence of relapse, independently of GVHD. Recent investigations in murine leukemia suggest that GVL-like effects may be inducible following syngeneic BMT by recombinant cytokines with no overt GVHD. Taken together, current data in experimental animals and man suggest that GVL may be at least partially separable from GVHD. Hence, further understanding of effector and target cells of GVL as well as our ability to induce antitumor effector cells, especially those that are MHC nonrestricted, may lead to new approaches for potentiating anti-tumor effector mechanisms without inducing severe, clinically overt GVHD. Successful attempts in these directions may also lead to improved results following autologous BMT as a result of activation of GVL-like effects by recombinant cytokines that are capable of activating effector cells with anti-leukemic activity in vivo, such as recombinant human IL2, alpha interferon or perhaps a synergistic combination of factors.
Bone Marrow Transplant 1990 Sep
PMID:The graft-versus-leukemia (GVL) phenomenon: is GVL separable from GVHD? 225 54

Pentaglobin is a commercial immunoglobulin preparation which is enriched specifically for IgM and also contains antibodies that are capable of neutralizing endotoxins. Its potential use in treating patients with acute graft-versus-host disease (GVHD) was studied in a phase I/II study. Pentaglobin was administered at a dose of 8 ml/kg/day for 4 days as a continuous infusion to 10 patients after allogeneic marrow transplantation who had histologically documented moderate grade II (n = 8) or moderately severe acute GVHD grade III (n = 2), and who did not require immediate treatment with steroids. There were no side effects related to the infusion of Pentaglobin and in all cases the serum concentrations of IgA, IgG and IgM at least doubled. Improvement of GVHD was seen in five patients with grade II GVHD. Conversely, in three patients with grade II and two patients with grade III GVHD, the disease either progressed during Pentaglobin infusion and required steroid treatment or showed no change and required steroids later in the course. Pentaglobin, therefore, might have some effect on mild and moderate GVHD. Randomized trials should be able to determine whether Pentaglobin could be considered as part of the GVHD prophylaxis or as adjunct treatment for acute GVHD together with low doses of steroids.
Bone Marrow Transplant 1990 Sep
PMID:Use of an immunoglobulin preparation enriched for IgM (Pentaglobin) for the treatment of acute graft-versus-host disease. 225 60

A case of disseminated infection with Trichosporon capitatum is reported in a 23-year-old patient with acute myeloid leukemia undergoing HLA-mismatched bone marrow transplantation. He was receiving immunosuppressive therapy with cyclosporine and corticosteroids for acute graft-versus-host disease and he was severely neutropenic. While being treated with fluconazole for 28 days for an oropharyngeal candidiasis the patient developed a T. capitatum septicemia. He died despite receiving amphotericin B therapy. Autopsy revealed widespread infection with T. capitatum. The portal of entry was probably the digestive tract in this patient as T. capitatum had been first isolated in the stools.
Bone Marrow Transplant 1990 Sep
PMID:Disseminated Trichosporon capitatum infection in a patient with acute leukemia undergoing bone marrow transplantation. 225 63

The development of airflow obstruction, most often due to bronchiolitis, is a significant cause of morbidity and mortality in recipients of allogeneic BMT. Current consensus holds that this airways disease is the result of chronic GVHD and/or CMV infection. However, recent studies of idiopathic forms of BRO have demonstrated a striking influx of neutrophils into the lungs of affected individuals. Reasoning that the immune cell populations involved in tissue injury associated with either CGVHD or CMV infection would consist predominantly of lymphocytes, we tested this hypothesis by performing BAL in 12 adults with minimal or absent smoking histories who developed significant airflow obstruction (FEV1/FVC = 80.7 +/- 1 percent preBMT and 56.8 +/- 2.4 percent postBMT; p less than 0.001) following allogeneic BMT. Eleven of 12 patients had evidence of chronic, stable GVHD at the time of the study. In contrast to non-BMT patients with BRO, BAL defined two distinct patterns of lung inflammation in the BMT patients with airflow obstruction: (a) neutrophil predominance (five patients; neutrophil percentage = 20.2 +/- 6.6 percent); and (b) lymphocyte predominance (three patients; lymphocyte percentage = 35.9 +/- 12.1 percent). These data suggest that the pattern of inflammation in the lungs of BMT patients with BRO is not uniform and is not associated with active microbial infection. From these results, it is inferred that the airways injury in BMT patients may reflect diverse pathogenetic mechanisms initiated in the context of CGVHD and cytotoxic drug therapy.
Chest 1990 Sep
PMID:Analysis of airflow obstruction by bronchoalveolar lavage following bone marrow transplantation. Implications for pathogenesis and treatment. 239 38

The present studies dealt with the pathogenesis of renal involvement in murine chronic graft-versus-host disease, which is a model for human systemic lupus erythematosus. The disease was induced in (C57BL10xDBA/2)F1 hybrids by injection of DBA/2 lymphocytes. The animals developed systemic disease accompanied by deposition of autoantibodies in the glomeruli and a lupus type of nephritis. Antibodies were eluted from glomeruli isolated during various stages of the disease by magnetic extraction from iron-perfused kidneys. For assessment of the specificity of the antibodies, we used indirect immunofluorescence, an enzyme-linked immunosorbent assay, and immunoblotting. In glomeruli from week 4, autoantibodies were found to be directed against several antigens, among which were the glomerular basement membrane component laminin and the glomerular enzyme dipeptidyl peptidase IV, whereas week 8 glomeruli also showed antibodies directed against nuclear antigens. Both laminin and dipeptidyl peptidase IV are known nephritogenic antigens occurring in renal tubular epithelial brush border preparations. Antibodies eluted from isolated glomeruli of diseased animals bound in a granular pattern along the glomerular capillary wall after in vivo transfer. Anti-renal tubular epithelial antibodies in the sera of diseased animals were affinity purified and injected into naive mice, which induced immune complex glomerulonephritis and proteinuria, thus confirming the nephritogenic role of these autoantibodies in this model.
Lab Invest 1990 Sep
PMID:Characterization and in vivo transfer of nephritogenic autoantibodies directed against dipeptidyl peptidase IV and laminin in experimental lupus nephritis. 239 30

From 1976 through 1985, the United States Food and Drug Administration received reports of 355 fatalities associated with transfusion, 99 of which were excluded from further review because they were unrelated to transfusion or involved hepatitis or acquired immune deficiency syndrome. Of the remaining 256 reported deaths, 51 percent resulted from acute hemolysis following the transfusion of ABO-incompatible products. These deaths were due primarily to managerial, not clerical, errors. Other causes of death (in order of frequency of report) included acute pulmonary injury (15%), bacterial contamination of product (10%), delayed hemolysis (10%), damaged product (3%), and graft-versus-host disease (0.4%). Management systems for transfusion facilities should be created or revised to include the specific identification of personnel eligible to administer transfusions to provide written guidance and appropriate training (including recognition and management of errors), and to implement measures that target safe transfusion practices. Continued research into acute pulmonary injury, the immunologic hazards of transfusion, and the prevention of bacterial contamination of blood components is necessary.
Transfusion 1990 Sep
PMID:Reports of 355 transfusion-associated deaths: 1976 through 1985. 240 71

The effect of different schedules of cyclosporine treatment on the survival of small bowel allografts was studied in rats. The administration of a short course of CsA (15 mg/kg on days 0, 1, 2, 4, and 6) had no beneficial effect on graft-vs.-host disease and survival time of the recipient compared with untreated controls. CsA, 25 mg/kg for 1 or 2 weeks prolonged survival significantly (38.3 +/- 3.8 and 42.5 +/- 2.7 vs. 16.6 +/- 2.7, P less than 0.01). When combined with maintenance therapy, 15 mg/kg of CsA 3 times weekly until day 100, only 7 of 30 rats survived more than 100 days. In addition, GVHD was not consistently abrogated in these groups. Only high doses of CsA (25 mg/kg on days 0-6, 15 mg/kg on days 7-13, followed by maintenance therapy) could prevent the onset of GVHD, although the survival time of the transplants was not prolonged compared with untreated controls due to a toxic side effect of CsA on the transplants. It can be concluded that CsA used as monotherapy is ineffective in consistently ameliorating GVHD and rejection in the WAG-BN rat model. This model exhibits at least some of the immunological problems seen in large animal models and can be useful in studying combinations of immunosuppressive drugs or methods that may be applicable to small bowel transplantation in man.
Transplantation 1990 Sep
PMID:The limited efficacy of cyclosporine in preventing rejection and graft-versus-host disease in orthotopic small bowel transplantation in rats. 240 84

Serum IgA levels were monitored at 3, 6, 12, and 24 months after BMT in 131 allogeneic and 3 syngeneic bone marrow transplant recipients. In general, IgA levels were low during the first 6 months and did not return to normal levels until 1-2 years after transplantation. Children (less than 15 years) had lower IgA levels at 3 and 6 months post-BMT compared to the adults (P less than 0.05), but donor age had no influence on the recipient IgA levels after BMT. Patients receiving either methotrexate or cyclosporine alone for GVHD prophylaxis had markedly lower IgA levels compared to those given a combination of these two drugs or patients transplanted with T-cell-depleted marrow (P less than 0.001). Mean IgA levels in patients without or with grade I acute GVHD were within the normal range at 3, 6, 12, and 24 months after BMT (greater than 0.3 g/L), although approximately 20% of the patients in each group showed low IgA levels (less than or equal to 0.3 g/L) early after transplantation. Patients with grade II or III acute GVHD had significantly lower values from 3 months up to 2 years after transplantation (P less than 0.01). Patients with chronic GVHD had significantly lower IgA levels 1 and 2 years after BMT compared to patients without chronic GVHD (P less than 0.005). Severe acute GVHD, particularly when followed by chronic GVHD, seems to be the main reason for low IgA levels, while other factors such as CMV infection or donor status may also contribute to the development of IgA deficiency after BMT.
Transplantation 1990 Sep
PMID:Development of IgA deficiency after bone marrow transplantation. The influence of acute and chronic graft-versus-host disease. 240 90

The feasibility and toxicity of six-week continuous intravenous 3 mg/kg/day cyclosporine (CsA) treatment in conjunction with a short course of methotrexate (MTX) was studied in 69 consecutive patients after HLA genotypically identical bone marrow transplantation. In light of the uncertain efficacy of prolonged oral CsA immunoprophylaxis in preventing de novo chronic graft-versus-host disease (GVHD). CsA treatment was terminated three months after BMT. Sixty-one (88%) patients received the full intravenous regimen and no patient exclusions were necessary due to intolerable adverse effects. Weekly median blood CsA concentrations ranged between 820 ng/ml in the first and 648 ng/ml in the sixth week of treatment. No significant correlation existed between blood CsA concentrations and CsA dosages. Major adverse effects of the regimen included hypertension in 36%, acute nephrotoxicity in 36%, acute hepatotoxicity in 41%, and central nervous system toxicity in 4% of the patients. Since hepatotoxicity occurred predominantly in the early posttransplant period (median onset day 9), the relatively high incidence of this untoward effect might have been additionally caused by MTX and/or the preparative regimen. Blood CsA concentrations and CsA dosages did not significantly correlate with serum creatinine or total and conjugated bilirubin levels. In addition, blood CsA and serum creatinine levels did not differ between hypertensive and normotensive patients. Acute GVHD developed in 16% of the patients. Median CsA doses and blood CsA concentrations were identical for each week after BMT for patients contracting acute GVHD as compared with those without acute GVHD. In 55 patients surviving without acute or secondary chronic GVHD, the cumulative probability of de novo chronic GVHD after termination of CsA treatment was 13%. In conclusion, this regimen was tolerable and provided constant blood CsA concentrations for six posttransplant weeks that were not adversely influenced by the development of acute GVHD. Restriction of CsA treatment to the first three months after BMT appeared not to increase the risk of de novo chronic GVHD, which challenges regimens employing oral CsA immunoprophylaxis for 6-12 months after BMT.
Transplantation 1990 Sep
PMID:Six weeks of continuous intravenous cyclosporine and short-course methotrexate as prophylaxis for acute graft-versus-host disease after allogeneic bone marrow transplantation. 240 91


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