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)

We reviewed the medical records of 97 patients undergoing T cell-depleted allogeneic bone marrow transplantation at our institution from 1984 to 1990 to determine the incidence of hepatic dysfunction, including venoocclusive disease of the liver following BMT. All patients received allogeneic marrow that had been purged with monoclonal antibody to the CD6 surface antigen (T12) and rabbit complement as the sole method of graft-versus-host disease prophylaxis. No additional immunosuppressive agents were routinely administered to these patients. Overall, 55% of patients in our series developed two-fold elevations in serum bilirubin, SGOT, or alkaline phosphatase within the first 30 days following BMT. A five-fold elevation in any liver function test was noted in only 19% of patients. Logistic regression analysis revealed that the presence of GVHD, female sex, and administration of amphotericin B all were independently associated with laboratory evidence of hepatic dysfunction. While LFT abnormalities were common in our series, they were generally mild, and the development of VOD was rare. Only three patients (3.1%) fulfilled clinical criteria sufficient to establish a diagnosis of VOD. Among the 86 patients whose ablative regimen consisted of cyclophosphamide (60 mg/kg x2) and total-body irradiation (1200-1400 cGy in 200 cGy fractions), only 1 patient (1.2%) developed VOD. Our experience suggests that patients undergoing allogeneic BMT are at low risk for VOD and other serious hepatic complications when they receive high-dose cyclophosphamide, fractionated TBI, and T cell-depleted marrow without hepatotoxic medications for GVHD prophylaxis.
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PMID:Hepatic dysfunction following T-cell-depleted allogeneic bone marrow transplantation. 175 63

Neopterin is a pyrazino-pyrimidine compound which is biosynthesized by macrophages. Increased concentrations of neopterin have been reported in conditions causing stimulation of cellular immunity, such as viral and other infections, graft versus host disease, autoimmune diseases and different malignancies. Recently, increased urinary neopterin levels have been found in patients with acute viral hepatitis and NANB chronic hepatitis. In the present study, neopterin serum levels were measured in 23 cirrhotic patients (6 HBV related, 7 alcoholic and 10 cryptogenetic cirrhosis) and in 24 normal subjects. Mean values of serum neopterin were statistically 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 statistically different either in cirrhotics assessed in three different classes according to Child's classification or in cirrhotics with or without serological findings of active disease. In fact, in cirrhotic patients, serum neopterin levels did not correlate with serum aspartate and alanine aminotransferases, alkaline phosphatase, gamma-glutamyltransferase and gammaglobulins values. These data show that increased levels of serum neopterin occur in cirrhotic patients, but there is no relation between serum neopterin values and the histological activity or the clinical severity of the disease. The results are consistent with the hypothesis that activated macrophages are involved in all forms and in all stages of liver cirrhosis.
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PMID:[Blood levels of neopterin in patients with liver cirrhosis]. 248 6

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

Leukocyte transfusions from patients with chronic myelogenous leukemia (CML) and elevated WBC counts were given to 14 patients with acute leukemia for the treatment of 16 infectious episodes. The WBCs were not irradiated to determine if engraftment with production of granulocytes would occur following infusion of immature myeloid elements. No recipient was alloimmunized by clinical and serologic criteria. High leukocyte yields were obtained using a variety of differential centrifugation techniques with a mean WBC yield/transfusion of 95 X 10(9) (range 19-275). A mean of 2.5 transfusions (range 1-11) were administered/recipient with a mean total dose of 235 X 10(9) WBC/transfusion episode (range 50-590). Seven patients had granulocyte counts greater than 500/microliters for four or more days (range 4-11 days) following the last transfusion. Ph1 chromosomes were documented in 2 of 4 patients tested 2-8 days following transfusion. Leukocyte alkaline phosphatase scores were increased (greater than 150) in 5/5 recipients tested post-transfusion demonstrating that production of this enzyme can be induced in CML granulocytes. Except for one severe transfusion reaction, there were no significant side effects and no recipient developed signs of graft versus host disease. All patients with sustained increments demonstrated rapid clinical improvement including 3 severely infected, poor risk patients undergoing initial induction therapy. These 3 patients all achieved complete remission with no evidence of the Ph1 chromosome. Because of the high dose of WBC which can be collected and the salutary effect of continued leukocyte production, CML WBC may be the preparation of choice for selected, non-alloimmunized, severely infected patients.
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PMID:Sustained post-transfusion granulocyte count increments following transfusion of leukocytes obtained from donors with chronic myelogenous leukemia. 657 31

Veno-occlusive disease continues to be a significant cause of morbidity and early mortality following bone marrow transplantation. This study retrospectively analyzes the incidence and risk factors for severe VOD in 350 patients treated with 4 days of busulfan (total 16 mg/kg) and 2 days of cyclophosphamide (120 mg/kg) at four marrow transplant centers. Using the criteria defined by McDonald et al (Hepatology 1984; 4: 116-122), 93/350 (27%) developed VOD (11% mild, 5% moderate and 11% severe). Multivariate analysis revealed the following risk factors to be significantly associated with severe VOD: pretransplant transaminase and alkaline phosphatase elevation, ciprofloxacin antibiotic prophylaxis, use of estrogen/progestins or vancomycin during the peritransplant period and methotrexate for GVHD prophylaxis. Mild to moderate grades of VOD were not associated with significantly increased mortality but mortality was higher in patients with severe VOD (31%, P = 0.0013). These data suggest that risk factors for VOD may depend on the preparative regimen used and suggest that use of these risk factors may identify a subgroup of patients that can be targetted for studies of prevention of VOD.
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PMID:Hepatic dysfunction following busulfan and cyclophosphamide myeloablation: a retrospective, multicenter analysis. 883 11

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

Hepatic graft-versus-host disease (GVHD) generally presents as cholestatic jaundice, and increased serum alkaline phosphatase (ALP) is followed by hyperbilirubinemia and clinical jaundice. Currently accepted standards for evaluating the clinical severity of GVHD are based not on serum aminotransferase levels but on the serum bilirubin level. We describe a 17-year-old Japanese female who had increased aminotransferases without cholestasis on day 23 after allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Liver biopsy revealed lymphocytic infiltration of the portal tracts and pericentral necrosis of the lobuli. The limiting plates were not clearly defined due to cellular infiltrates. There was periductal lymphocytic infiltration and vacuolization of the biliary epithelial cells with exocytosis, compatible with GVHD of cholangiohepatitic type. These findings indicate that acute hepatic GVHD may present as acute hepatitis and this should be included in the differential diagnosis for patients with increased aminotransferases after allogeneic stem cell transplantation.
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PMID:Hepatic graft-versus-host disease presenting as an acute hepatitis after allogeneic peripheral blood stem cell transplantation. 1143 13

We investigated graft-versus-host disease (GVHD)-specific survival (GSS) and the duration of systemic immunosuppressive treatment (IST) in 82 patients who developed chronic GVHD following allogeneic haematopoietic cell transplantation (HCT). These two major study endpoints were calculated using the Kaplan-Meier method. Deaths solely due to the relapse of underlying disease or accidental deaths were censored at the time of occurrence for the analysis of GSS. The probability of GSS at 5 years was 74.2%. The median duration of systemic IST for chronic GVHD was 272 d (range: 7-1450), and the probability of withdrawal of systemic IST at 1, 2 and 3 years was 67.3%, 82.4% and 89.0% respectively. Analysis based on a multivariate model showed that a diagnosis other than leukaemia or myelodysplastic syndrome (P = 0.049), prior occurrence of grade III-IV acute GVHD (P = 0.021), onset of chronic GVHD before d 120 (P = 0.013), serum alkaline phosphatase over 120 IU/l (P = 0.034), and serum bilirubin over 34.2 micromol/l (P = 0.015) were independent adverse prognostic factors for GSS. Prior occurrence of grade III-IV acute GVHD significantly influenced the duration of systemic IST (P = 0.048). In conclusion, analyses of GSS and the duration of systemic IST will allow patients with different outcomes to be stratified for appropriate treatment application and will provide important parameters in prospective trials for the treatment of chronic GVHD.
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PMID:Graft-versus-host disease (GVHD)-specific survival and duration of systemic immunosuppressive treatment in patients who developed chronic GVHD following allogeneic haematopoietic cell transplantation. 1289 19

Hepatic graft-versus-host disease (GVHD) post allogeneic hematopoietic stem cell transplantation generally presents as cholestatic jaundice and increased serum alkaline phosphatase (ALK-P). Currently accepted standards for evaluating the clinical severity of hepatic GVHD are not based on serum aminotransferase levels but on the serum bilirubin levels. We describe a 25-year-old female who initially had no liver damage at all after an allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from her HLA-indentical sister. Markedly elevated aminotransferases, without hyperbilirubinemia, however, developed 7 and 9 weeks after the first and second donor lymphocyte infusion (DLI), respectively. Liver biopsies performed in both events revealed lymphocytic infiltration of the portal tracts and pericentral necrosis of the lobuli. There was also a picture of periductal lymphocytic infiltration and vacuolization of the biliary epithelial cells, which was compatible with the diagnosis of GVHD of cholangiohepatitic type. These findings indicate that hepatic GVHD may present as acute hepatitis and should be included in the differential diagnosis for patients with increased aminotransferases after DLI.
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PMID:Donor lymphocyte infusion induced acute hepatitis. 1555 1


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