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)

Cyclosporin A was given to five patients with acute leukaemia in whom graft-versus-host disease (G.V.H.D.) had developed after bone-marrow transplantation from sibling donors. In all instances the acute erythematous skin reaction of G.V.H.D. resolved within two days, but four of the five patients died. Cyclosporin A in high doses produced anorexia, nausea, and a reversible rise in blood-urea. The four patients who died all had liver damage, but the histological changes varied. Cyclosporin A modifies the acute skin reaction of G.V.H.D. In the management of liver and gut G.V.H.D., and in prophylaxis of G.V.H.D., its role needs to be determined.
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PMID:Cyclosporin A for the treatment of graft-versus-host disease in man. 8 37

The potentially beneficial effect of 8-methoxypsoralen and ultraviolet A (PUVA) irradiation for treatment of drug-resistant cutaneous manifestations of graft-versus-host disease led us to investigate the effect of this therapy in a larger series of patients with GvHD. To date, 11 patients with histologically demonstrated cutaneous GvHD (acute GvHD grade III-IV in 4 patients, extensive lichenoid chronic GvHD in 6 patients, sclerodermatous chronic GvHD in 1 patient) have received PUVA treatment for 2-24 weeks. All patients have been on CsA for GvH prophylaxis; 5 with mismatched grafts had additionally received methotrexate or monoclonal antibody campath-1 after bone marrow transplantation. Seven patients were on CsA and prednisolone; 2 patients on CsA, prednisolone, and azathioprine; 1 patient on azathioprine and prednisolone; and 1 patient had no immunosuppressive treatment for the duration of PUVA treatment. The 8-methoxypsoralen (0.6 mg/kg bw) was given as photosensitizer before each ultraviolet A irradiation (0.3-8.5 joules/cm2). The only observed adverse reaction was mild nausea. In all patients improvement of cutaneous lesions could be observed with complete response in 5 patients and partial response in 6 patients. Immunosuppressive drugs could be withdrawn in 2 patients and reduced in 8 patients after initiation of PUVA treatment. These findings suggest that PUVA therapy may be a useful adjunct to conventional therapy for cutaneous GvHD.
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PMID:8-Methoxypsoralen and ultraviolet A therapy for cutaneous manifestations of graft-versus-host disease. 223 56

Recognized manifestations of acute graft-versus-host disease (GVHD) of the gastrointestinal (GI) tract include secretory diarrhea, abdominal pain, and, at times, hemorrhage. In a review of 469 patients undergoing allogeneic bone marrow transplantation (BMT) from matched sibling donors at our institution, we have recognized a syndrome of upper GI GVHD. This syndrome, presenting clinically as anorexia, dyspepsia, food intolerance, nausea, and vomiting, was recognized and confirmed histologically in 62 patients (13% by Kaplan-Meier projection) at the initiation of systemic GVHD therapy, a subset of the 197 patients developing grade II through IV GVHD. These 62 patients with upper GI GVHD were significantly older than the overall BMT population and older than the cohort with grade II through IV GVHD, as well. Of the 62 patients, 25 had upper GI GVHD accompanied only by limited (stage 1 and 2) skin GVHD; 13 others with upper GI GVHD plus limited skin involvement at initial presentation later progressed to more extensive multiorgan involvement; 24 others presented with upper GI along with other organ GVHD. This upper GI GVHD syndrome, first recognized at our center in 1983, has been diagnosed with increasing frequency (22% +/- 5%) in the most recent 5-year interval. The upper GI GVHD syndrome is more responsive to immunosuppressive therapy than grade II GVHD defined by Seattle criteria, with complete and continuing responses to treatment observed in 71% +/- 17% (95% confidence interval) of those with the upper GI GVHD syndrome compared with only 37% +/- 10% complete responses in other patients with grade II GVHD (P = .002). Patients failing immunosuppressive therapy for upper GI GVHD often progress to symptomatic lower GI involvement, suggesting that this syndrome may be an earlier and perhaps more treatable manifestation of this unique intestinal immunopathology, which is followed by chronic GVHD in 74% of patients. While upper GI GVHD symptoms are nonspecific and require invasive histologic and microbiologic studies to confirm the diagnosis, we believe this syndrome has been underreported after allogeneic BMT and propose its recognition within the clinical GVHD scoring system.
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PMID:Acute upper gastrointestinal graft-versus-host disease: clinical significance and response to immunosuppressive therapy. 237 89

Overwhelming secretory diarrhea can be a major complication after bone marrow transplantation, associated usually with acute graft-versus-host disease (AGVHD). Radiographic evaluation may be hampered by nausea, vomiting, or debilitation. Computed tomography (CT) in seven such patients demonstrated diffuse wall thickening in the small intestine, colon, and/or mesentery. In two cases, prolonged adherence of oral contrast material to the luminal surface resulted in bizarre patterns of coating. In two others, a layer of low attenuation within the thickened wall produced a target appearance consistent with submucosal edema or hemorrhage. Small bowel dilatation and fold enlargement was the only finding in one patient. The role that superinfection of the gastrointestinal tract with opportunistic organisms can play in this immunocompromised group of patients is less well established. In this group of patients, the findings were due to AGVHD in two, AGVHD and viral enteritis in two, and viral enteritis alone in three. CT may be an alternative to routine contrast studies in assessing the extent of gastrointestinal tract involvement after bone marrow transplantation. Neither contrast studies nor CT were able to differentiate between AGVHD and viral enteritis.
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PMID:Computed tomography of gastrointestinal inflammation after bone marrow transplantation. 351 88

Twenty-two stomach and 14 small intestinal biopsy specimens from 24 allogeneic bone marrow transplant recipients were reviewed to evaluate the histopathologic changes of graft-versus-host disease (GVHD) in these organs. Associations between these results and clinical symptoms and other biopsy results were sought. In both organs, single epithelial cell necrosis was found to correlate with GVHD. Gastric GVHD was diagnosed in eight patients and small intestinal GVHD in four. Gastric GVHD was characterized by nausea, vomiting, and upper abdominal pain without diarrhea (the latter being present in only two patients), while all four of the patients with small intestinal GVHD had upper gastrointestinal symptoms and diarrhea. These symptoms correlated with concurrent rectal biopsy findings; pathologic alterations were seen in only one of six specimens from patients with gastric GVHD but in three of four with small intestinal GVHD. These findings suggest that stomach biopsy may be necessary to diagnose GVHD in patients with upper gastrointestinal symptoms but no diarrhea and normal rectal biopsy specimens. Diagnostic problems may arise in the early posttransplantation period, when the effects of cytoreductive therapy may simulate GVHD, and in patients with gastrointestinal cytomegalovirus infection, which may also produce changes identical to those of GVHD.
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PMID:A histopathologic study of gastric and small intestinal graft-versus-host disease following allogeneic bone marrow transplantation. 388 82

A 23-year-old woman gravely ill with Pseudomonas septicemia secondary to presumed drug-induced bone marrow aplasia received marrow transplantation from two male HL-A identical sibling donors. She had a successful engraftment with excellent but temporary clinical improvement. Subsequently she succumbed to graft-versus-host disease manifested by Pseudomonas and Candida albicans septicemia, cytomegalovirus pneumonitis, three phases of dermatitis, nausea, vomiting, dysphagia, diarrhea, fever, edema and bone pain, with gradual but complete graft suppression by the 74th day after the transplantation. A second marrow transplant on the 70th day was unsuccessful.
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PMID:Bone marrow transplantation in a patient with drug-induced aplastic anemia. 440 93

Grading acute graft-versus-host disease (GVHD) is usually based on quantification of rash, serum bilirubin and diarrhea. Standard criteria have been developed and used for > 20 years by most transplant centers. However, neither the standard GVHD grading system nor any of several revisions has been validated in the context of GVHD prophylaxis with cyclosporine. The 1994 Consensus Conference on Acute GVHD Grading held in Keystone in January 1994 provided an opportunity to: (1) review data regarding these standard criteria; (2) determine if there are sufficient data to revise these criteria; and (3) develop recommendations for reporting results of GVHD prevention trials. Data were provided for 8249 patients from 12 large transplant centers and 2 transplant registries. Standard GVHD grading criteria were found to distinguish different mortality risks and treatment response rates. Analysis of new data suggested that persistent nausea with histologic evidence of GVHD but no diarrhea be included as stage 1 gastrointestinal GVHD. Additional studies were recommended to evaluate heterogeneity of outcome within GVHD grades prior to making further revisions. To improve comparability between publications, reports of GVHD prevention trials should include an accurate description of the grading system used and should report actuarial rates of grades II-IV and III-IV GVHD corrected for graft failure and potential interventions for early relapse. Additional information should include indications for therapy of GVHD and response.
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PMID:1994 Consensus Conference on Acute GVHD Grading. 758 Oct 76

This study evaluated the acute toxicity of trimetrexate (TMTX) used in combination with cyclosporine (CsA) for prevention of acute graft-versus-host disease (GVHD) in patients undergoing allogeneic marrow transplantation from HLA-mismatched, related donors. TMTX has a mechanism of action similar to that of methotrexate (MTX); however, unlike MTX, TMTX is not primarily dependent on renal excretion. Patients were conditioned for transplant with cyclophosphamide, anti-thymocyte globulin, and total body irradiation. TMTX, 10 mg/m2 i.v., was administered on days 1, 3, 6, 11, 18, 25, 32, and 39 after transplant. CsA, 1.5 mg/kg i.v., was administered every 12 hr beginning on day-1. Eleven patients with hematologic malignancies or aplastic anemia (median age = 34 yr) received TMTX. Toxicity assessed included nausea, vomiting, fever, rash, time to myeloid and platelet engraftment, mucositis, and hepatic and renal dysfunction. Toxicity of TMTX was not different from that observed with MTX in a similar patient population. One patient died on day 16 before engraftment. The other 10 patients all engrafted and all developed acute GVHD at a median time of 11 days after transplant. The major manifestation of acute GVHD was in the skin, and all but one patient responded to primary therapy with corticosteroids. Seven patients have survived a median of 447 days after transplant. No significant toxicity from TMTX was observed. Further trials are warranted to define the role of TMTX in marrow transplantation.
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PMID:A toxicity study of trimetrexate used in combination with cyclosporine as acute graft-versus-host disease prophylaxis in HLA-mismatched, related donor bone marrow transplants. 762 43

Intestinal graft-versus-host disease (GVHD) causes anorexia, vomiting, abdominal pain, and diarrhea. We investigated oral beclomethasone dipropionate (BDP), a potent, topically active corticosteroid, as therapy for this disease. Forty-two allogeneic marrow-graft recipients with biopsy-proven intestinal graft-versus-host disease of mild-to-moderate severity received BDP (8 mg daily) for up to 28 days. Weekly symptom scores, oral intake, and surveillance throat and stool cultures were compared with baseline values. Adrenal testing was performed serially in patients not receiving concurrent prednisone. Improvement was seen in appetite (P < 0.001), oral intake (P < 0.001), nausea (P = 0.013), and diarrhea (P = 0.02) over the course of therapy, and an overall beneficial response was observed in 72% of 40 evaluable patients. Surveillance cultures of throat and stool showed no increase in bacterial or fungal colonization over time. The adrenal axis became suppressed in 11 of 20 evaluable patients (55%) but suppression was not a prerequisite for clinical response, as 6 of 9 patients who retained normal adrenal function improved clinically. We conclude that oral BDP is a safe and effective treatment for mild-to-moderate intestinal graft-versus-host disease. Systemic absorption probably occurs, but adrenal suppression is not a prerequisite for clinical efficacy, suggesting that the biological effect is primarily topical. BDP should be further investigated as a topical therapy for intestinal GVHD.
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PMID:Oral beclomethasone dipropionate for treatment of human intestinal graft-versus-host disease. 852 16

FK506 (Tacrolimus) is an immunosuppressive drug that blocks the activation of antigen-specific T lymphocytes, a major component in the pathogenesis of graft-versus-host disease (GVHD). This study was designed to obtain first estimates of the safety and efficacy of FK506 monotherapy in the prevention of GVHD following HLA-identical sibling marrow transplantation. Additionally, a subset of patients was studied to define the pharmacokinetic profile of FK506. Twenty-seven adult patients with leukemia or myelodysplasia received FK506 starting the day before transplant at a dose of 0.04 mg/kg/d by continuous intravenous infusion. When clinically possible, FK506 was given orally in two divided doses starting at five times the daily intravenous dose. FK506 doses were adjusted to target a steady state or trough blood level between 10 to 30 ng/mL. These patients were followed for 6 months posttransplant. All patients had sustained marrow engraftment. Frequently noted adverse events included reversible renal dysfunction, diarrhea, fever, nausea, vomiting, and headache. Most patients required FK506 dose reductions associated with elevated serum creatinine. Two (7%) patients relapsed, one of whom died of the disease within the 6-month study period. A second patient died due to pulmonary mucor. Whole blood pharmacokinetic parameters indicated a half-life of 18.2 +/- 12.1 hours; volume of distribution of 1.67 +/- 1.02 L/kg; clearance of 71 +/- 34 mL/h/kg; and bioavailability of 32 +/- 24%. Eleven of 27 (41%) patients developed grade II to IV acute GVHD, including 10 grade II and one grade III. Six of 24 (25%) evaluable patients developed chronic GVHD. These data indicate that FK506 monotherapy has activity in preventing GVHD. Further studies of FK506 with lower doses to improve tolerability and in combination with other immunosuppressants to augment efficacy are warranted.
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PMID:FK506 (Tacrolimus) monotherapy for prevention of graft-versus-host disease after histocompatible sibling allogenic bone marrow transplantation. 860 72


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