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)

A 20-year-old Chinese male given an HLA-identical sibling bone marrow transplant for severe aplastic anemia, who had previously had chronic graft-versus-host disease (GVHD) of the mouth, developed myasthenia gravis and widespread pulmonary infiltrates with cough and exertional dyspnea at day 820 post-transplant. There was nothing to suggest aspiration pneumonia. Lung histology at day 940 showed some areas of dense pulmonary fibrosis, some areas of normal parenchyma, and some areas of widening of the interstitium and a mild lymphocytic infiltrate. Evidence of infection was not found. Treatment with cyclosporin and prednisone resulted in slow partial resolution of the infiltrates over 5 months. The myasthenia gravis was controlled with pyridostigmine. In view of the association with myasthenia gravis, of the absence of infectious agents and the response to immunosuppression, we conclude that widespread pulmonary fibrosis can be a major clinical manifestation of chronic GVHD. Examination of lung tissue to distinguish this from infective interstitial pneumonitis is essential.
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PMID:Widespread pulmonary fibrosis as a major clinical manifestation of chronic graft-versus-host disease. 264 79

The cumulative incidence of chronic graft-versus-host disease (GVHD) was 48% among 165 patients with severe aplastic anemia who had been discharged from Seattle 3 months after they were treated with marrow grafts from HLA-identical siblings. Estimated 10-year survival was 85%. Preceding acute GVHD had a dominating influence on the development of chronic GVHD. Almost all patients with grades II-IV and 67% of those with grade I acute GVHD developed chronic GVHD. Among patients without previous acute GVHD, three factors were independently correlated with an increased risk of de novo chronic GVHD: increasing patient age, the infusion of buffy coat cells in addition to the marrow, and corticosteroid therapy before transplantation. For example, patients below and above age 20 years who had neither buffy coat cell transfusions nor preceding corticosteroid therapy had an incidence of chronic GVHD of only 4-8%, while those with either buffy coat cell transfusions or corticosteroids or both had incidence rates of 33-70%. The development of chronic GVHD significantly influenced survival. Among 83 patients without chronic GVHD, only one died (on day 150 with interstitial pneumonia), compared to 23 deaths among 82 patients with chronic GVHD. For results of marrow grafting for aplastic anemia to improve, better prevention of chronic GVHD is needed.
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PMID:Factors predicting chronic graft-versus-host disease and survival after marrow transplantation for aplastic anemia. 265 Jul 84

Interstitial pneumonitis and biopsy-proven pulmonary fibrosis developed in a 35-year-old man with acute myeloblastic leukemia 4 months after conditioning with total body irradiation, etoposide and cyclophosphamide and allogeneic marrow transplantation from an HLA-identical sister. The patient had no evidence of graft-versus-host disease. Under treatment with cyclosporine and prednisone the patient became asymptomatic and radiographic changes of the chest normalized. Following discontinuation of immunosuppressive treatment the patient again became dyspneic, and chest radiographs showed bilateral diffuse interstitial infiltrates. Concurrently there was a rise in serum transaminases. Treatment with prednisone again resulted in resolution of all symptoms and normalization of radiographic and hepatic function abnormalities. This case indicates that late onset interstitial pneumonitis may respond to immunosuppressive therapy. Conceivably, such pulmonary disease may represent the first or only manifestation of chronic graft-versus-host disease.
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PMID:Pulmonary fibrosis after bone marrow transplantation responsive to treatment with prednisone and cyclosporine. 265 Jul 91

Data from 547 patients with aplastic anaemia who received bone marrow transplants from HLA-identical siblings were analysed to determine factors associated with the risk of interstitial pneumonia (IPn). IPn developed in 92 patients (17%). 37% of cases were associated with cytomegalovirus infection and 22% with other organisms; in 41% of cases no organism was identified. The case fatality rate was 64%; the mortality rate due to IPn was 11%. In multivariate analysis, four factors were associated with an increased probability of interstitial pneumonia: use of methotrexate rather than cyclosporine after transplantation (relative risk, 2.8; P less than 0.0008); occurrence of moderate to severe acute graft-versus-host disease (relative risk, 2.2; P less than 0.002); inclusion of total body radiation in the pretransplant preparative regimen (relative risk 2.2, P less than 0.004); and patient age greater than 20 (relative risk 1.7, P less than 0.002). The probability of IPn ranged from 4% for patients with none of these adverse risk factors to 51% (relative risk of 13.4) for patients with all four. The incidence of IPn decreased significantly between 1978 and 1985, paralleling a decrease in the use of total body radiation pretransplant for immune suppression and methotrexate post-transplant for prophylaxis against graft-versus-host disease.
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PMID:Risk factors for interstitial pneumonia following bone marrow transplantation for severe aplastic anaemia. 265 9

On April 26, 1986, an accident at the Chernobyl nuclear power station in the Soviet Union exposed about 200 people to large doses of total-body radiation. Thirteen persons exposed to estimated total-body doses of 5.6 to 13.4 Gy received bone marrow transplants. Two transplant recipients, who received estimated doses of radiation of 5.6 and 8.7 Gy, are alive more than three years after the accident. The others died of various causes, including burns (the cause of death in five), interstitial pneumonitis (three), graft-versus-host disease (two), and acute renal failure and adult respiratory distress syndrome (one). There was hematopoietic (granulocytic) recovery in nine transplant recipients who could be evaluated, six of whom had transient partial engraftment before the recovery of their own marrow. Graft-versus-host disease was diagnosed clinically in four persons and suspected in two others. Although the recovery of endogenous hematopoiesis may occur after exposure to radiation doses of 5.6 to 13.4 Gy, we do not know whether it is more likely after the transient engraftment of transplanted stem cells. Because large doses of radiation affect multiple systems, bone marrow recovery does not necessarily ensure survival. Furthermore, the risk of graft-versus-host disease must be considered when the benefits of this treatment are being weighed.
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PMID:Bone marrow transplantation after the Chernobyl nuclear accident. 274 61

We evaluated relapse-free survival and the incidence and type of complications in 17 patients aged 40 or older with chronic myelogenous leukemia, acute myelogenous leukemia, or lymphoma who underwent allogeneic marrow transplantation following busulfan 16 mg/kg and cyclophosphamide 120 mg/kg. Nine patients are disease-free survivors 5-38 months (median 26 months) following transplantation. The incidence of grades II-IV acute graft-versus-host disease was 35%. No significant difference was detected in the incidence of GVHD or interstitial pneumonia between patients aged 40 and older and a group of younger patients transplanted over the same time period. These observations should encourage consideration of allogeneic marrow transplantation in older patients and suggest that this busulfan-cyclophosphamide regimen is a promising alternative to regimens containing total-body irradiation in older individuals.
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PMID:Bone marrow transplantation without total-body irradiation in patients aged 40 and older. 266 38

We report a single center experience of 222 patients (pts) less than 18 years old transplanted from 1973 to 1987. The median age was 11 years (1-18). The donor was a monozygotic twin (9 pts), an HLA-id sibling (193 pts), an HLA-id, parent (9 pts), a mismatched related donor (9 pts) and a matched unrelated donor (1 pt). Ninety-six pts were transplanted for SAA. Conditioning varied with time but the majority (59 pts) received CY 150 mg/kg and 6 Gy TAI. The long term actuarial survival is 66% with a median follow-up of 3 years. The group who received CY 200 mg/kg and MTX had a 33% long term survival (LTS). GVH was the main complication with 40% acute and 37% chronic GVHD. Chronic GVHD tended to improve with time after 2 to 4 years of evolution. Ninety pts were transplanted for leukemia (35 AML, 45 ALL and 11 CGL), 20 pts were in relapse. Pts in CR had a LTS of 40%, in pts in relapse, it was 12%. The main causes of death were: interstitial pneumonitis (30%), relapse (27%), GVH (15%). Thirty-five pts were transplanted for constitutional disease: Fanconi anemia (FA) (26 pts), Dyskeratosis congenita (2 pts), Blackfan-Diamond erythroblastopenia (2 pts), Glanzmann thrombasthenia (1 pt), osteopetrosis (1 pt) and Gaucher's disease (1 pt). In FA, the LTS is 70% with a CY 20 mg/kg, 5 Gy TAI regimen. In all disease categories, we did not find any influence of donor's sex on GVH and survival.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pediatric bone marrow transplantation for leukemia and aplastic anemia. Report of 222 cases transplanted in a single center. 267 24

Data from 3113 patients receiving HLA-identical sibling bone marrow transplants for leukemia were analysed to determine the time course of the major causes of treatment failure. The median interval from transplant to onset of acute graft-versus-host disease (GVHD) was 17 days, interstitial pneumonitis 63 days, and chronic GVHD 111 days. The median interval from transplant to relapse was 3.3 months for patients transplanted in relapse of acute leukemia or blast phase of chronic myelogenous leukemia (CML), 6.4 months when transplants were performed in second or subsequent remission of acute leukemia or accelerated phase of CML, and 7.8 months for patients transplanted during first remission of acute leukemia or while in the first chronic phase of CML. Shorter intervals from transplant to onset of interstitial pneumonitis or chronic GVHD were associated with a significantly lower probability of 2-year survival. The temporal relationships between these complications are displayed graphically and demonstrate the overlapping and competing causes of death following allogeneic bone marrow transplantation.
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PMID:Temporal relationships between the major complications of bone marrow transplantation for leukemia. 267 53

One-hundred and five patients undergoing allogeneic bone marrow transplantation (BMT) for acute myeloid leukaemia (AML) (n = 61) and chronic myeloid leukaemia (n = 44) were analysed for risk factors associated with relapse. All patients received marrow from an HLA identical sibling after preparation with cyclophosphamide 120 mg/kg and total body irradiation (TBI) 330 cGy on each of the three days prior to transplantation. There was a difference of +/- 18% between the nominal total dose of 990 cGy and the actual dose received as indicated by dosimetric recordings. While interstitial pneumonitis had minimal impact on survival (4%) there was a considerable difference in the incidence of relapses. The incidence of relapse was 55% versus 11% in patients receiving less or more than 990 cGy respectively and this had a major impact on survival (38% v. 74% at 7 years) since transplant-related mortality was comparable in the two groups. A multivariate Cox analysis indicated that a lower TBI dose (less than 990 cGy) was the most significant factor associated with relapse and the second most important factor associated with recurrence of leukaemia was the absence of chronic graft-versus-host-disease (cGvHD). Actuarial relapse incidence was 62%. 28% and 18% for patients with no, limited or extensive chronic GvHD respectively. However, chronic GVHD had no significant impact on survival. Combined stratification for TBI dose and cGvHD showed that the dose effect of TBI on relapse was evident both in patients with and without cGvHD. Chronic GvHD influenced the risk of relapse only in patients receiving less than 990 cGy. These results suggest that a higher dose of TBI, within this schedule, produced long-term disease-free survival in the majority of AMLs and CMLs. Minor radiobiological side effects were experienced but a small reduction of the dose may significantly increase the risk of relapse.
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PMID:The effect of total body irradiation dose and chronic graft-versus-host disease on leukaemic relapse after allogeneic bone marrow transplantation. 268 59

Infections continue to be common complications of bone marrow transplantation, but recent advances have improved their outcome. Oral chemoprophylaxis with the fluoroquinolones has reduced gram-negative infections during periods of granulocytopenia, while new triazole drugs show promise for improving antifungal prophylaxis. Similarly, recombinant hematopoietic growth factors may reduce infections by shortening the period of post-transplant granulocytopenia. The efficacy of double beta-lactam antibiotic therapy or monotherapy with imipenem has obviated the need to use aminoglycosides in the empiric treatment of febrile patients receiving cyclosporine or other nephrotoxic agents. Treatment of post-transplant interstitial pneumonia associated with cytomegalovirus (CMV) remains problematic, but recent results using the combination of ganciclovir plus intravenous immune globulin have been favorable. In CMV-seronegative patients, CMV infections and pneumonia can be prevented or modified by using CMV-seronegative blood products and intravenous immune globulin. Intravenous immune globulin also has the additional benefits of modifying graft versus host disease and preventing late bacterial infections after marrow engraftment. In CMV-seropositive patients, prophylactic ganciclovir may prevent CMV reactivation and pneumonia and is the subject of an ongoing controlled clinical trial.
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PMID:Current approaches to management of infections in bone marrow transplants. 269 7


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