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)

Ursodiol is a hydrophilic, non-hepatotoxic bile salt indicated for the medical treatment of cholesterol gallstones. This pilot study explored the use of prophylactic ursodiol in an attempt to decrease the incidence and severity of veno-occlusive disease (VOD) of the liver following allogeneic bone marrow transplantation (BMT). Between February 1991 and January 1992, 22 consecutive patients undergoing BMT for hematologic malignancies received the BU(4)/CY(2) preparative regimen and CSA/MTX for GVHD prophylaxis. Ursodiol, 600-900 mg daily by mouth was begun at least 1 day prior to beginning the preparative regimen. Results for this pilot group were compared to a control group of 28 consecutive patients transplanted between June 1989 and January 1991 with the same regimen without ursodiol. There were no significant differences in disease or clinical status between the groups pretransplant. However, mean baseline AST levels were significantly higher in the ursodiol group, 28.0 U/l vs 18.1 U/l in the control group (p = 0.001). The median maximum bilirubin observed post-transplant was 2.35 mg/dl (range 0.9-45) in the ursodiol group, and 5.05 mg/dl (range 0.7-29.4) in controls. The incidence of VOD was 2/22 (9.1%) in the ursodiol group and 18/28 (64.3%) in controls (p = 0.0001). Death due to VOD occurred in 1/22 patients (4.5%) in the ursodiol group and in 6/28 (21.4%) controls (p = 0.12). Our data suggest that ursodiol may decrease the incidence of VOD in allogeneic BMT patients.
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PMID:Pilot trial of prophylactic ursodiol to decrease the incidence of veno-occlusive disease of the liver in allogeneic bone marrow transplant patients. 142 93

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

The diagnostic efficacy of five serum liver function tests (aspartate and alanine aminotransferase, alkaline phosphatase, 5' nucleotidase, and bilirubin) was investigated in 95 bone marrow transplant recipients in whom acute graft-vs-host disease was graded by the Seattle criteria. The patient population included a control group of 22 autologous transplant recipients (group I), 33 patients with no GVHD (group II), 21 patients with grades 1 and 2 GVHD (group III), 12 patients with grade 3 GVHD (group IV), and 7 patients with grade 4 GVHD (group V). Student t test analysis of the analytes among the five groups of patients showed that 5' nucleotidase and alkaline phosphatase were the best discriminants among all the possible combinations of group pairs. Peak levels of 5' nucleotidase within each group of patients correlated well with those of alkaline phosphatase in all the allogeneic transplant groups (II-V; r = 0.59), but the correlation of these with bilirubin was less frequent. Also, 5' nucleotidase and alkaline phosphatase showed significant discrimination (P less than 0.05) even between groups I and II, suggesting that they are more sensitive than the Seattle criteria in the diagnosis of GVHD. They also showed the best overall discriminatory ability by one-factor analysis of variance (ANOVA; P = 0.0001 as compared with 0.002, 0.009, and 0.04 for aspartate aminotransferase, alanine aminotransferase, and bilirubin, respectively). Receiver-operating curves of the five analytes again revealed that 5' nucleotidase and alkaline phosphatase were by far the best discriminators among the five groups of patients. Bilirubin was relatively insensitive because it was a good discriminator only between the control group and groups IV and V. The hepatocellular enzymes, alanine and aspartate aminotransferase, correlated well (r = 0.80) but discriminated poorly among the four groups of allogeneic transplant recipients (II-V), suggesting that all four groups had some measure of hepatocellular damage that was independent of the severity of GVHD.
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PMID:Serum 5'nucleotidase and alkaline phosphatase--highly predictive liver function tests for the diagnosis of graft-versus-host disease in bone marrow transplant recipients. 255 45

Neopterin is a pyrazino-pyrimidine compound which is biosynthesized by macrophages. Increased concentrations of neopterin have been reported in conditions causing a stimulation of cellular immunity, such as viral and other infections, graft versus host disease, autoimmune disease and different malignancies. Recently, urinary neopterin levels have been found increased in patients with acute viral hepatitis and NANB chronic hepatitis. In the present study, neopterin serum levels have been measured in 23 cirrhotic patients (6 HBV related, and 17 cryptogenetic cirrhosis, 7 of them occurring in alcoholic subjects) and in 24 normal subjects. Mean values of serum neopterin were significantly increased in cirrhotics (3.92 +/- 3.28 ng/ml versus 1.24 +/- 0.51 ng/ml in controls, p less than 0.01). Serum neopterin values were not found to be significantly different in cirrhotics assessed in three different clinical classes according to Child's classification and in cirrhotics with and without serological findings of active disease. In fact, in cirrhotic patients, serum neopterin levels did not correlate with the values of serum AST, ALT, ALP, GGT and gamma-globulin. These data show that increased levels of serum neopterin occur in cirrhotic patients, but there is no relation between serum neopterin values and the activity or the clinical severity of the disease. The results are consistent with the hypothesis that activated macrophages are involved in all stages of liver cirrhosis irrespective of its aetiology.
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PMID:Serum neopterin levels in liver cirrhosis. 263 48

The value of routine chronic graft-versus-host disease (GVHD) screening studies performed between 70 and 120 days after allogeneic marrow transplantation was retrospectively evaluated among 241 patients. All patients received methotrexate and cyclosporine for GVHD prophylaxis and survived without relapse more than 4 months after transplant. Ninety-one patients (38%) developed clinical extensive chronic GVHD requiring systemic therapy. Data on patients who developed clinical extensive chronic GVHD were compared with those on patients without chronic GVHD to determine which of the following screening tests predicted the subsequent development of clinical extensive chronic GVHD: skin biopsy, oral exam, lip biopsy, Schirmer's test, serum alkaline phosphatase, aspartate transaminase, immunoglobulin level and platelet count. In a univariable analysis, a positive oral examination and a low platelet count were predictive of chronic extensive GVHD development. In a multivariable analysis which adjusted for the contribution of other chronic GVHD risk factors, such as age and a history of acute GVHD none of the screening tests were predictive of chronic GVHD development. The risk factors in this multivariable analysis which had the strongest association with the development of chronic GVHD was a history of acute GVHD and use of corticosteroids at day 100 (RR = 3.9, P = 0.001). The use of corticosteroids for acute GVHD at day 100 had a predictive effect on chronic GVHD development independent of the grade of acute GVHD (RR = 2.1, P = 0.004). Based on these study results, the use of chronic GVHD screening tests may not be of value in predicting who will develop this complication. Patients on corticosteroids at day 100 should be considered for clinical trials to determine the efficacy of new immunosuppressive agents in preventing chronic GVHD.
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PMID:The development of chronic graft-versus-host disease: an analysis of screening studies and the impact of corticosteroid use at 100 days after transplantation. 970 21

Before the introduction of routine blood donor screening in 1991, marrow transplant recipients were at significant transfusion-associated risk for infection with hepatitis C virus (HCV). We followed a cohort of 355 patients undergoing transplant in Seattle during 1987 to 1988 to determine (1) the impact of pretransplant HCV infection on the occurrence and severity of venocclusive disease (VOD); (2) the impact of HCV infection on liver dysfunction, other than VOD, occurring between 21 and 60 days after transplantation; and (3) the natural history of post-transplant HCV liver disease with a 10-year follow-up. HCV-RNA status was determined on serum stored before transplant and at day 100 post-transplant. Sixty-two (17%) patients were HCV-RNA positive before transplant, and 113 (32%) were HCV-RNA positive by day 100 post-transplant (or before death). Severe VOD developed in 22 of 46 (48%) evaluable patients with pretransplant HCV infection and in 150 of 229 (14%) evaluable patients without HCV (P <.0001). In multivariable analysis of risk factors for developing VOD, pretransplant HCV infection associated with elevated serum aspartate transaminase (AST) levels predicted the development of severe VOD (relative risk, 9.6; P =.0001). The presence of HCV with normal AST levels before transplant was not a risk factor for severe VOD. Between 21 and 60 days after transplant, HCV-RNA positive-patients had higher AST levels (median 101 U/L), but similar alkaline phosphatase and total bilirubin levels compared with HCV-negative patients, suggesting that cholestatic liver disease (particularly graft-versus-host disease [GVHD]) was not related to HCV infection. An acute flare of hepatitis (AST >10 times the upper limit of normal) developed at a mean of 136 +/- 58 days in 31% of HCV-positive patients; no patients developed fulminant hepatitis. Between 5 and 10 years after transplant, 57% of HCV-positive and 6% of HCV-negative patients had mild to moderate elevations of AST (P <. 0001), but HCV infection was not associated with excess mortality between 3 and 10 years after bone marrow transplantation. In summary, HCV infection with elevated AST levels is a significant risk factor for severe VOD after marrow transplant. However, the decision to proceed to transplantation in HCV-positive patients must balance the absolute risk of death from VOD against the risks of the underlying disease. In long-term survivors, HCV infection is not associated with excess mortality over 10 years of follow-up.
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PMID:Hepatitis C virus infection and bone marrow transplantation: a cohort study with 10-year follow-up. 1034 35

Hepatocyte growth factor (HGF) was reported to be effective in preventing acute graft-versus-host disease (GVHD) in a murine model. We examined serum HGF concentrations in 38 patients receiving allogeneic bone marrow transplants, and investigated the relationship of serum HGF concentrations to severity of acute GVHD. More HGF was present in sera from patients with than without acute GVHD. Serum HGF correlated significantly with grade of acute GVHD. Furthermore, serum HGF correlated with serum concentrations of C-reactive protein, gamma-glutamyltranspeptidase (GTP), and aspartate aminotransferase (AST). Serum concentrations of HGF in transplanted patients without GVHD were consistently low, while those in patients with acute GVHD increased with exacerbation. We conclude that HGF was produced during induction of the GVH reaction, and probably increased as a physiological response.
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PMID:Increased hepatocyte growth factor in serum in acute graft-versus-host disease. 1150 38

Graft-versus-host disease (GVHD) of the liver is characterized by bile duct damage and portal lymphocytic infiltrate. We report acute hepatitislike presentation of GVHD after donor lymphocyte infusion (DLI). Between April 1998 and September 2001, 73 patients received 94 DLI treatments. Liver GVHD developed after DLI in 22 (30%) patients whose median age was 43 years (range, 21 to 61 years). Onset of liver dysfunction was at 35 days (range, 11 to 406 days) after DLI. Fifteen patients underwent liver biopsy, and the diagnosis of liver GVHD was confirmed in 13 (87%) patients. After viral hepatitis and recent drug exposure were excluded, 11 (50%) patients were given a diagnosis of a hepatitic variant of GVHD based on histologic evidence of lobular hepatitis (n = 5), elevation of maximum serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level more than 10 times the upper normal limit (n = 9), or both. There was a significant difference in maximum ALT (P =.002) and AST (P =.01) level between the hepatitic-variant and classical GVHD groups. GVHD progressed in 14 (64%) patients, and 10 patients died after a median follow-up of 221 days (range, 31-1284 days). These observations suggest that GVHD that occurs after DLI may have distinct clinical features. Hepatitic-variant GVHD should be considered in the differential diagnosis in DLI recipients with unexplained hepatitis.
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PMID:Hepatitic variant of graft-versus-host disease after donor lymphocyte infusion. 1239 29

Busulfan (Bu) is an important component of some myeloablative regimens prior to stem cell transplantation (SCT). Over the last few years it has been shown that other drugs administered concomitantly can influence Bu pharmacokinetics. In the present study, we compared Bu concentrations (trough levels) in three groups of patients. Group A (n=5) received metronidazole as graft-versus-host disease prophylaxis during Bu treatment. Group B (n=9) received Bu only for 2 days followed by 2 days of Bu and metronidazole. Group C (n=10) was a control group that received Bu without metronidazole. The mean Bu levels for Group A receiving metronidazole during conditioning was significantly (P<0.001) higher (948+/-280 ng/ml), compared to those observed in the control group (507+/-75 ng/ml). In Group B, the administration of metronidazole resulted in a significant (P<0.001) increase in Bu levels (807+/-90 ng/ml) during the last 2 days, compared to 452+/-68 ng/ml during the first 2 days. In Group A, one patient died with multiorgan failure, three experienced veno-occlusive disease (VOD) and one developed hemorrhagic cystitis. Elevated liver transaminases (AST, ALT) and bilirubin were detected in all Group A patients. In Group B, six patients had elevated liver function tests but no VOD was observed. We conclude that metronidazole should not be administered simultaneously with Bu to avoid the high plasma levels of Bu, which may lead to severe toxicity and/or treatment related mortality.
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PMID:The effect of metronidazole on busulfan pharmacokinetics in patients undergoing hematopoietic stem cell transplantation. 1266 36

We retrospectively analyzed the factors that affect serum cyclosporine (CsA) concentrations up to day 14 after allogeneic hematopoietic stem cell transplantation (HSCT). In all, 103 transplant recipients who received MTX and CsA for acute GVHD prophylaxis were analyzed. No significant relationships between serum CsA concentrations and gender, age, serum creatinine levels, AST/ALT levels, or antibiotic/fluconazole administration were found by comparing median CsA concentrations or by using longitudinal or regression multivariate analyses. However, the mean of the median serum CsA concentration in patients (n=54) receiving the regimen containing cyclophosphamide (CY) (149.7 ng/ml; 95% confidence interval (CI): 132.1-167.4) was significantly (P<0.0001) lower than that in patients (n=49) receiving the non-CY regimen (217.3 ng/ml; 95% CI: 198.9-235.6). Longitudinal analysis and regression multivariate analysis showed that only administration of CY had a significant effect on the serum CsA concentration. Our results suggest that administration of CY during conditioning can reduce the effects on serum CsA concentrations during the 2 weeks following HSCT. The mechanism of this effect is not clear, but it may be due to the autoinduction of CY.
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PMID:Effect of cyclophosphamide on serum cyclosporine levels at the conditioning of hematopoietic stem cell transplantation. 1462 75


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