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)

87 patients underwent bone marrow transplantation (BMT) in Innsbruck between 1983 and 1992. 81 patients were suffering from hematologic malignancies and severe aplastic anemia and six patients had advanced solid tumours/sarcoma. 56% of the patients undergoing HLA-identical sibling BMT were in an advanced or refractory stage of disease at the time of BMT. 19 patients underwent autologous BMT and 5 patients received a graft from an HLA-matched unrelated donor. Patients were treated with standard conditioning regimens according to the underlying disease. Cyclosporine A (CsA) was given prophylactically against graft-versus-host disease (GVHD) either alone or in combination with methotrexate. Probability of survival for patients transplanted in the first chronic phase of chronic myelogenous leukemia (CML) was 85%, whereas the disease free survival (DFS) for patients transplanted in accelerated phase or blast crisis was only 40%. DFS for acute myelogenous leukemia (AML) in first complete remission and acute lymphoblastic leukemia (ALL) standard-risk (i.e., first or second complete remission) was 71% and 60%, respectively. All patients transplanted for non-Hodgkin's lymphoma (NHL) or Hodgkin's disease had refractory or advanced disease. Probability of survival for lymphoma patients was 60%. Acute GVHD > grade II developed in 35% of patients undergoing HLA-identical sibling BMT (46% in the high-risk group vs. 21% in the standard-risk group). Main causes of death in the high-risk group were relapse (31%), severe bacterial or fungal infections (17%), interstitial pneumonia (11%) and acute GVHD (6%).
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PMID:[Innsbruck results of bone marrow transplantation in treatment of hematologic neoplasms and solid tumors]. 819 54

The immunology, pathophysiology, incidence, clinical manifestations, grading, and prevention of acute graft-versus-host disease (GVHD) are reviewed. GVHD occurs after allogeneic marrow transplantation when immunologically competent T lymphocytes in the donor marrow identify the host's antigens as foreign and attempt to reject host tissues. Acute GVHD occurs within three months after marrow transplantation and may affect the skin, gastrointestinal tract, liver, and immune system. Even with prophylactic immunosuppression, acute GVHD occurs in 20% to 80% of patients. Moderate to severe GVHD (grades II-IV) is a major cause of morbidity and mortality after allogeneic bone marrow transplantation. Conventional GVHD prophylaxis consists of immunosuppressives such as corticosteroids, methotrexate, and cyclosporine. Methotrexate and cyclosporine are equally effective in preventing GVHD. A combination of both drugs is better than either drug alone and results in an improved survival rate. The addition of corticosteroids to methotrexate, cyclosporine, or antithymocyte globulin is also more effective than single-drug therapy. Serial administration of intravenous immune globulin may contribute additional protection against acute GVHD. There is conflicting evidence concerning the prophylactic efficacy of pentoxifylline. Elimination of T lymphocytes from the donor marrow before transplantation has been associated with less GVHD but a higher incidence of graft failure. Total elimination of GVHD in patients with leukemia may cause loss of a graft-versus-leukemia effect, resulting in increased relapse rates and decreased long-term survival. Promising experimental prophylactic agents include thalidomide, zolimomab aritox, tacrolimus, antibodies to cytokines involved in the pathogenesis of GVHD, and monoclonal antibodies against cytokine receptors on T lymphocytes. Current research efforts are also directed toward eliminating GVHD without compromising the graft-versus-leukemia effect.
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PMID:Pharmacologic prophylaxis of acute graft-versus-host disease after allogeneic marrow transplantation. 825 55

Acute graft-versus-host disease (GVHD) has recently been associated with endothelial cell injury. The potential clinical significance was explored here in an autopsy review. Thirty-seven allogeneic bone marrow recipients were identified in the autopsy files at The Johns Hopkins Hospital with no evidence of systemic infection. Forty-one percent (15/37) of these patients were found to have extensive recent pulmonary hemorrhage at autopsy which was thought to have led to terminal respiratory failure and death. The 37 patients were divided into 2 groups: those with significant acute GVHD (stage 2 or greater) and those without GVHD (stage 0 or 1). Fifty-nine percent (10/17) of the patients with significant acute GVHD died of acute respiratory failure due to recent pulmonary hemorrhage as opposed to 25% (5/20) of those without acute GVHD (P = 0.032, Fisher's exact test). Terminal pulmonary hemorrhage was also associated with preparation for BMT, with 67% (12/18) of those prepared with total body irradiation (TBI) having pulmonary hemorrhage as opposed to 15% (3/19) of those prepared with chemotherapy using Busulphan (P = 0.002). There was no significant difference in posttransplant survival, engraftment, or final platelet count between the patients stratified by GVHD or preparative protocol. The data support a strong association between significant acute GVHD and terminal hemorrhage, as well a possible association between TBI and pulmonary hemorrhage. Analysis of variance demonstrates that GVHD and TBI are independently associated with increased pulmonary hemorrhage (P < 0.01 for GVHD, P < 0.001 for TBI). We propose that GVHD contributes to terminal pulmonary hemorrhage by injuring the endothelium. However, this association could also be a secondary effect, i.e., toxicity from therapy for GVHD, or an abnormality in cytokines or growth factors. The pathogenic relationship between significant GVHD and terminal hemorrhage is discussed briefly.
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PMID:Pulmonary hemorrhage as a cause of death in allogeneic bone marrow recipients with severe acute graft-versus-host disease. 829 Nov 20

Unrelated donor (URD) bone marrow transplantation (BMT) is associated with more frequent and more therapy-resistant graft-versus-host disease (GVHD). We tested an in vivo immunotoxin with direct cytolytic potency against CD5-expressing T lymphocytes (Xomazyme-CD5) for GVHD prophylaxis after URD BMT. The immunotoxin was given in vivo (0.1 mg/kg/day) for 3 weeks following transplantation in combination with methotrexate+prednisone (MXP; n = 16) or methotrexate+cyclosporine (MCX; n = 6). The 22 patients (10 phenotypically matched with their donors and 12 partially matched) received unmanipulated marrow. MXP was well tolerated, while MCX led to unacceptable nephrotoxicity, weight gain and edema. Four patients died of early complications. Thirteen of 17 evaluable patients achieved myeloid engraftment by 17-40 days (median 24 days). Acute GVHD developed in 9 of 15 evaluable patients (5 grade III/IV). Six of 8 evaluable patients developed chronic GVHD. Four patients survive 1.1-2 years after BMT. Although this immunotoxin has previously shown potency in prophylaxis of murine GVHD and therapy of human GVHD, in this trial inadequate immunosuppressive potency of the immunotoxin combinations was associated with unacceptable clinical toxicity. Aggressive immunoprophylaxis against GVHD is required to improve the success of URD BMT.
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PMID:Combination graft-versus-host disease prophylaxis using immunotoxin (anti-CD5-RTA [Xomazyme-CD5]) plus methotrexate and cyclosporine or prednisone after unrelated donor marrow transplantation. 829 65

Cytostatic chemotherapy instead of supralethal total body irradiation (TBI) has been increasingly used as an alternative myeloablative regimen before bone marrow transplantation (BMT). While irreversible azoospermia/amenorrhoea seems to occur less frequently with such conditioning, graft-versus-host disease (GVHD) remains unaffected. Five-year disease-free survival in accelerated chronic granulocytic leukemia (CGL), after BMT with matched sibling grafts has been 0.10-0.30. Mitobronitol, cytosine arabinoside, and cyclophosphamide were used for conditioning. Patients were transplanted with unmanipulated HLA/MLC identical sibling bone marrow. For recovery, a pathogen-low room was available without air filtering and laminar airflow. Seven of eight accelerated-CGL patients were engrafted: full allogeneic reconstitution was detected in four and mixed chimerism in three patients. Five out of the seven engrafted patients survived at least nine months (median = 42 months), two are considered cured (8-9 years survival). The four leukemia-free survivors displayed full allogeneic reconstitution and presented symptoms of chronic GVHD. One patient became a genetically verified father. Acute GVHD and veno-occlusive liver disease (VOLD) were absent in all patients, diffuse interstitial pneumonitis (IP) occurred in one case. Non-supralethal conditioning with mitobronitol/cytarabine/cyclophosphamide in accelerated-CGL allows allogeneic bone marrow reconstitution with survival and cure rates comparable to those achieved with other protocols using TBI or busulphan conditioning. Unlike the latter treatments, however, our protocol leads to fewer transplant-related complications including acute GVHD, IP, VOLD, and azoospermia/amenorrhoea.
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PMID:Non-supralethal mitobronitol/cytarabine/cyclophosphamide conditioning without irradiation before bone marrow transplantation for accelerated chronic granulocytic leukemia: apparent absence of acute graft-versus-host disease. 832 Oct 45

The cyclosporine (CYA) metabolite patterns in blood were evaluated in patients with liver dysfunction after allogeneic BMT. Fifty-five BMT patients were included in the study until discharge from hospital. Blood trough levels of CYA and 12 of its metabolites were quantified using HPLC. The patients were assigned to three groups: group I (no acute GVHD, n = 23), group II (acute GVHD of the skin and good liver function, overall acute GVHD: grade I: n = 18, grade II: n = 2) and group III (acute GVHD and liver dysfunction, overall acute GVHD: grade II: n = 2, grade III/IV: n = 8). Analysis of the trough blood concentrations of CYA and its metabolites revealed higher concentrations of metabolite AM19 in group III than in the other groups without reaching statistical significance. During acute GVHD of the liver, the metabolites AM19 (p < 0.01), AM1c9 (p < 0.05) and AM1A (p < 0.05) were significantly elevated compared with patients with normal liver function while CYA and all other metabolites did not differ. The CYA metabolite pattern in patients with acute GVHD and liver involvement was identical with that of liver graft patients during acute graft rejection, while the metabolite patterns of the patients without acute GVHD paralleled that of kidney grafted patients with normal liver function. Acute GVHD of the liver leads to an impaired elimination of CYA with increased blood concentrations of single CYA metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclosporine metabolite pattern in blood from patients with acute GVHD after BMT. 837 34

Sixty-three recipients of an allogeneic marrow transplant were screened for the occurrence of cytomegalovirus (CMV) infection and clinical parameters possibly predicting the development of CMV disease in a retrospective study. Blood and urine samples obtained from these patients were screened weekly after bone marrow transplantation (BMT) for the presence of CMV by polymerase chain reaction (PCR) and virus culture technique. Forty-six of the 63 patients studied were found to be CMV-positive by PCR technique in blood and urine samples at a median of 29 days after BMT. In 33 of these 46 patients, CMV could be cultured from urine samples and 16 of the 46 had culture-positive viremia. Twenty-eight of these 46 PCR-positive patients developed CMV disease. Whereas PCR assays showed an optimal negative predictive value and sensitivity for the development of CMV disease, their positive predictive value was 61% and could not be remarkably increased when culture-proven viruria (64%) and viremia (69%) were considered. Acute graft-versus-host disease (GVHD) grade 2 to 4 (P < .05), but not underlying disease, conditioning therapy, or GVHD prophylaxis, was associated with CMV infection. On day +49, a remarkable decrease (P < .001) in the lymphocyte count, as well as in the absolute number of CD4+, CD8+, and CD56+ lymphocytes, occurred only among the patients who later developed CMV disease. The decrease of all of these cell counts, but predominantly the CD4+ T cells, to less than 100/microL on day +49 after BMT showed a very high positive predictive value (100%) for the development of CMV disease in patients with PCR-proven viremia. Persisting CD4 lymphopenia after antiviral therapy was only observed in patients who finally died of CMV disease. Thus, immunophenotyping of the patients after BMT in addition to a highly sensitive virus detection assay might help to identify patients at high risk to develop CMV disease and indicate the need for additional adoptive immunotherapy.
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PMID:Lymphocytopenia as an unfavorable prognostic factor in patients with cytomegalovirus infection after bone marrow transplantation. 839 13

We describe a male neonate with severe combined immunodeficiency who at birth had acute graft-versus-host disease (GVHD) as a result of maternal-fetal transfusion during pregnancy. Several clinical signs helped establish this diagnosis. Findings of a skin biopsy specimen confirmed the diagnosis of acute GVHD. Immunologic evaluation disclosed an absence of T and B lymphocytes. Acute GVHD in severe combined immunodeficiency most often occurs during the first weeks of life; intrauterine occurrence is unusual.
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PMID:In utero acute graft-versus-host disease in a neonate with severe combined immunodeficiency. 840 28

With the aim of evaluating liver disturbances after BMT in 76 patients, the hepatic venous pressure gradient was measured and a transvenous liver biopsy was performed through the jugular vein. Catheterization was successful in 71 patients (93%). In 11 cases the procedure was performed twice, yielding a total number of 82 studies. In five (6%) liver biopsies were non-evaluable. Complications were rare (7%), minor and reversible. As a result of this procedure, the diagnosis was modified in 45%, with both the diagnosis and treatment being modified in 30% of patients. Veno-occlusive disease (VOD) was histologically demonstrated in 15 out of 26 patients (58%) in whom this complication was suspected and in two out of 33 (6%) in whom it was not. Acute GVHD of the liver was confirmed in 15 out of the 35 patients (43%) in whom this complication was suspected and in four of 24 (17%) in whom it was not. The hepatic venous pressure gradient was significantly higher in VOD than in liver GVHD. Whereas 14/17 (82%) patients with VOD had a gradient pressure higher than 9 mmHg, no patient with GVHD had a gradient above this value. We conclude that transjugular liver biopsy is an effective, safe, and useful technique to evaluate BMT related liver dysfunction.
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PMID:Transjugular liver biopsy in BMT. 843 7

2-3 antigens mismatched BMT were performed on 32 children without a matched sibling donor. In the light of previous in vitro studies, which suggested a role of Vincristine and Methilprednisolone ex vivo treatment in modulating alloreactivity of T cells, bone marrow was treated with such a pharmacological cocktail before being infused. Acute GVHD 2 degrees to 4 degrees degree occurred in 46% of cases, chronic GVHD in 28%, graft failure in 13%. There was no significant difference between 2- and 3-antigens mismatched BMT as far as GVHD and graft failure are concerned.
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PMID:Low incidence of GvHD and rejection after pharmacological ex vivo modulation of bone marrow in 2-3 antigens mismatched BMT. 844 33


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