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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)

Bone marrow transplantation has become an accepted procedure for the treatment of severe aplastic anemia, hematologic malignancies (particularly lymphoma and leukemia) and certain inborn errors of metabolism and immunity. However, numerous complications follow bone marrow transplantation. Liver disease is a very common and complex complication after human transplantation. The major complications are: veno-occlusive disease, graft-versus-host disease acute and/or chronic. In this decade, the results of bone marrow transplantation will enhance.
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PMID:[Hepatic complications of bone marrow transplantation]. 184 69

Twenty patients who were positive for hepatitis B surface antigen (HBsAg) underwent allogeneic marrow transplant for malignancy or other underlying hematologic disease between 1975 and 1986. After transplant, one patient had serologic evidence of hepatitis B virus (HBV) reactivation whereas three patients had evidence of an immune response to HBV. Among four patients with serologic follow-up of 1 year or more, three remained positive for HBsAg and one became HBsAg negative. Six patients (30%) developed clinical evidence of venocclusive disease and seven patients (35%) developed acute graft-versus-host disease involving the liver, but the incidence of these complications was similar to that expected among patients who are not carriers of HBsAg. Three patients died with hepatorenal failure, but all three had venocclusive disease and the contribution of HBV infection to liver failure was unclear. Available liver specimens obtained at autopsy (six patients) or biopsy (two patients) all showed either HBsAg (one specimen) or hepatitis B core antigen (four specimens) or both (three specimens) by immunoperoxidase staining. Although HBV reactivation leading to hepatic failure has been reported among allogeneic marrow transplant recipients as well as other immunocompromised patients, we did not observe an increase in the incidence of severe liver disease after transplant among these 20 patients positive for HBsAg at the time of transplant, and do not consider positivity for HBsAg to be a contraindication to allogeneic marrow transplantation.
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PMID:Allogeneic marrow transplantation in patients positive for hepatitis B surface antigen. 198 95

We have reviewed results of secondary therapy in 427 patients with acute graft-versus-host disease (GVHD) who did not have a durable satisfactory response after primary treatment. At the beginning of secondary treatment, 320 patients (75%) had rash, 252 (59%) had liver dysfunction, and 228 (53%) had gut dysfunction. Secondary treatment was with glucocorticoids (n = 249), cyclosporine (n = 80), antithymocyte globulin (n = 114), or monoclonal antibody (n = 19) either singly (n = 390) or in combination (n = 37). Parameters of GVHD severity were recorded weekly, and responses were determined according to values at the initiation of tertiary treatment or, for patients without such treatment, using values on day 29 of secondary treatment or the last recorded values before death, whichever occurred first. Minimal criteria for improvement or deterioration were defined for each organ, but no attempt was made to define liver or gut outcome if another complication such as venocclusive disease or infectious enteritis was present. Improvement or resolution of GVHD in the respective organ was seen in 45% of patients with skin disease, 25% of patients with evaluable liver disease, and in 35% of patients with evaluable gut disease. Overall complete or partial responses were seen in 40% of patients. The highest complete response rate with secondary therapy (23%) was seen when GVHD recurred during the taper phase of primary glucocorticoid treatment and was managed by increasing the dose of glucocorticoids. Multivariate analyses were performed to identify patient, disease, or treatment factors associated with likelihood of complete response or overall improvement. A similar analysis was performed to identify covariates associated with time to treatment failure (defined as initiation of tertiary therapy or death not due to relapse of malignancy). Severe dysfunction in the skin, liver, and gut at the beginning of treatment was associated both with a decreased likelihood of complete response and an increased treatment failure rate. The times to treatment failure and the proportions of patients in various response categories were similar for primary and secondary treatment, suggesting that the potential efficacy of new immunosuppressive agents for treatment of acute GVHD can be assessed meaningfully in patients who have not responded adequately to initial therapy.
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PMID:A retrospective analysis of therapy for acute graft-versus-host disease: secondary treatment. 201 5

A 73-year-old man developed graft-versus-host disease (GVHD) after blood transfusion; he developed hepatitis, fever, rash, and pancytopenia. Although similar cases have been previously reported, the spectra of their liver injury was not clarified. The clinical and pathological findings of this case and a review of earlier reports suggest a possible predominance of hepatocellular injury in cases of GVHD after blood transfusion, which is in contrast to the prevalence of cholestatic liver disease in GVHD following bone marrow transplantation.
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PMID:Hepatic involvement in graft-versus-host disease associated with blood transfusion. 210 15

We have reviewed results of therapy in 740 patients with grades II-IV acute graft-versus-host disease (GVHD) after allogeneic marrow transplantation. At the beginning of therapy, 597 patients (81%) had rash, 369 (50%) had liver dysfunction and 396 (54%) had gut dysfunction. Initial treatment was with glucocorticoids (n = 531), cyclosporine (n = 170), antithymocyte globulin (ATG) (n = 156) or monoclonal antibody (n = 3) either singly (n = 633) or in combination (n = 107). Parameters of GVHD severity in each organ were recorded weekly, and evaluation of response was made using values at the initiation of secondary treatment or, for patients without such treatment, using values on day 29 of primary treatment or the last recorded value before death, whichever occurred first. Minimal criteria for improvement or progression were defined for each organ, but no attempt was made to define liver or gut outcome if another complication such as venocclusive disease or infectious enteritis was present. Improvement rates were 43% for skin disease, 35% for evaluable liver disease and 50% for evaluable gut disease. Overall complete or partial responses were seen in 44% of patients. Multivariate analyses were carried out to identify patient, disease or treatment factors associated with likelihood of overall improvement and likelihood of response in at least one organ. A similar analysis was also carried out to identify covariates associated with time to treatment failure (defined as initiation of secondary therapy or death not due to relapse of malignancy). In all three models, GVHD prophylaxis using cyclosporine combined with methotrexate was associated with favorable GVHD treatment outcome compared to prophylaxis with either agent alone, and treatment with glucocorticoids or cyclosporine was more successful than treatment with ATG. Other factors associated with unfavorable outcome in the model of time to treatment failure and also entered in one of the response models were recipient HLA disparity with the donor, presence of a liver complication other than GVHD, and early onset of GVHD. Results of this analysis indicate that glucocorticoids represent the best initial therapy available for treatment of acute GVHD, although much room for improvement remains.
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PMID:A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment. 220 21

Increasingly, bone marrow transplant (BMT) is the treatment of choice for certain hematologic diseases. BMT is, however, a risky procedure with many potentially serious complications. Some complications are the result of the conditioning regimen, a stage of transplantation that includes large doses of chemotherapy and/or radiation therapy. Conditioning-induced neutropenia and thrombocytopenia often result in infection, bleeding, and mucositis. Veno-occlusive disease (VOD), a chemotherapy-induced hepatotoxicity, can cause a mild to severe form of liver disease. Other complications are directly attributable to the engrafted new marrow. Graft-versus-host disease, a rejection process initiated by immunocompetent donor T lymphocytes, is a complication frequently observed in allogeneic BMT. Approximately 14-28 days after the day of transplant, signs of engraftment begin to appear. When specific discharge criteria are met, the BMT patient is discharged from the hospital. Specific follow-up medical care is ongoing for about one year after BMT.
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PMID:Post-bone marrow transplant patient management. 229 8

Forty-three patients with hematopoietic disease were treated with intensive chemotherapy and radiotherapy, followed by allogeneic bone marrow transplantation (BMT) from 28 HLA-identical and 10 one to two antigen haploidentical sibling donors and autologous BMT (5 cases). Of these cases, there were 21 with acute nonlymphocytic leukemia (ANLL), 5 with acute lymphocytic leukemia (ALL), 6 with chronic myelocytic leukemia (CML), 2 with Hodgkin's disease (HD), 8 with severe-form aplastic anemia (SAA) and 1 with thalassemia. Complications of BMT were evaluated including acute graft-versus-host disease (GVHD), interstitial pneumonia (IP), veno-occlusive liver disease (VOD), abnormalities of liver function (LF), and alteration of hepatitis B virus (HBV) markers. In thirty-three patients who were followed up for more than 3 months, we found that the incidence of moderate to severe acute GVHD (9.1%) and IP (two cases, 4.7%) were low. No VOD occurred in our series. During the follow-up period, 27 out of 35 patients (77%) had high alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels, even up to 1000 U/liter; however, only one patient succumbed to a hepatitis-related complication. Previous hepatic damage from HBV infection before BMT does not appear to increase the risk of posttransplant morbidity and mortality.
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PMID:Complications of bone marrow transplantation in Chinese. 232 72

A murine IgG1 antibody specific for the IL-2-binding site on the human lymphocyte IL-2 receptor beta chain (CD25) was evaluated in 11 patients who developed acute graft-versus-host disease following allogeneic marrow transplantation. All patients had received cyclosporine and methotrexate for prophylaxis of GVHD, either alone (4 cases), or in combination with antithymocyte globulin (4 cases) or with prednisone (3 cases). Patients had developed GVHD at 7-53 days (median 12) after transplantation and had failed treatment with corticosteroids for 3-44 days (median 19). Residual GVHD was of grade II severity in 4 patients, grade III in 5 patients, and grade IV in 2 patients. Sequential patients received monoclonal antibody in escalating doses from 0.1 mg/kg/day to 1.0 mg/kg/day for 7 days. Side effects were fever, respiratory distress, hypertension, hypotension, and chills occurring in 11 of 72 (14%) antibody infusions. Trough antibody levels greater than 6 micrograms/ml were achieved in patients treated with 0.5 or 1.0 mg/kg/day. Four of eight evaluable patients had an IgM antibody response, and one had an IgG response to the murine immunoglobulin. Clinical response of GVHD was evaluated in 10 patients who received the entire course of the antibody treatment. Among 7 patients treated within 40 days from transplantation, one patient had a complete response in the skin as the only involved organ, and 3 patients had a partial response, 2 in the skin and one in the gastrointestinal tract. No responses were achieved with liver disease at anytime or in any organ in patients treated beyond 40 days after transplantation. Since administration of this antibody was well tolerated and some efficacy was observed in patients with acute GVHD treated early after transplantation, there is a rationale for testing this antibody as an agent for prophylaxis of GVHD.
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PMID:A phase I-II study evaluating the murine anti-IL-2 receptor antibody 2A3 for treatment of acute graft-versus-host disease. 236 50

The epithelium of the biliary tree is involved in the response to numerous liver disease processes including immunologic destruction during liver transplant rejection and liver graft-versus-host disease after bone marrow transplantation. Furthermore, very little is known concerning the function of this previously inaccessible epithelium, because attempts to isolate and culture biliary cells have been unsuccessful until recently. We present a method for the isolation and culture of bile ductular cells from mice with external bile duct obstruction. Over 85% of the isolated cells stain positive for cytokeratin 19, which is characteristic of murine biliary epithelium. Incubation with recombinant murine gamma-interferon resulted in increased class II antigen expression on the isolated cell surface. When these cells were placed, on a basement membrane matrix, they formed duct-like structures composed of cells that had the morphologic characteristics of bile ductular epithelium when examined by transmission electron microscopy. The ability to isolate murine biliary epithelium that forms duct-like structures will be useful for the in vitro study of biliary epithelial characteristics and injury.
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PMID:In vitro duct-like structure formation after isolation of bile ductular cells from a murine model. 247 64

This study was undertaken to evaluate the occurrence of VOD and other liver diseases following BMT in a patient population with a high incidence of hepatitis before conditioning regimen. We prospectively reviewed 186 consecutive patients undergoing BMT from 1976 to 1986 to determine incidence and type of liver disease after BMT and predisposing factors. Two of 186 patients experienced VOD (1.07%). Acute and chronic liver GVHD were found in 25.8% and 36% of the patients, respectively. Acute hepatitis (AH) was diagnosed in 29.4% and chronic hepatitis (CH) in 42.6% of the patients. Statistical analysis showed no influence of pretransplant variables on the occurrence of acute GVHD and AH; there was a weak correlation (P = 0.01) between pre-BMT abnormal transaminases and occurrence of chronic GVHD. Contingency table and Cox analysis showed a greater risk of CH for patients with abnormal pretransplant SGPT levels (P = 0.0004 and P = 0.0022). No other variables could be associated with posttransplant CH. Actuarial survival was 71% versus 69% for patients with normal versus abnormal transaminases (P = 0.2). As VOD was a rare event, despite 53% of patients having abnormal transaminase values before transplant, we suggest that a lower and slower TBI is more important than pretransplant normal transaminases in preventing this complication. We conclude that evidence of compensated hepatitis is not a relative contraindication for BMT.
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PMID:Predictability before transplant of hepatic complications following allogeneic bone marrow transplantation. 266 39


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