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 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

Tumor necrosis factor is one of the recently cloned cytokines with pleiotropic effects on normal and malignant cells. Our knowledge about the scope of cells producing or responding to this cytokine has enormously expanded. In critically ill patients with acute hepatic failure, acute graft-versus-host disease, or septic shock, circulating tumor necrosis factor can be measured and useful prognostic correlations do exist. Despite promising in vitro results, early clinical trials with tumor necrosis factor for the treatment of cancer have failed thus far to reveal major antineoplastic activity in cancer patients. However, more clinical trials are necessary, since different routes of administration and combinations with other cytokines may lead to favorable results.
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PMID:Tumor necrosis factor: an update on basic research and clinical applications. 221 7

A case of transfusion-induced graft-versus-host disease (GVHD) occurring in a 31-year-old female with Hodgkin's disease in complete remission is reported. Clinical features are similar to 19 other reported cases of transfusion-induced GVHD associated with malignant lymphoma. The lack of relationship with underlying histology or disease stage and the nearly uniformly fatal outcome underscores the importance of prophylactic irradiation of blood products given to patients with malignant lymphoma undergoing therapy.
Cancer 1990 Dec 01
PMID:Transfusion-induced graft-versus-host disease in patients with malignant lymphoma. A case report and review of the literature. 224 90

The indications and results of allogeneic bone marrow transplantation are well known by the analyses of European and International registries. In acute non-lymphoblastic leukemia in first complete remission (CR), the disease-free survival (DFS) is 45%, with a risk of relapse (RR) of 15%; in ALL in first CR the DFS is 60% with a RR of 15%; in ALL in second CR the DFS in 40%, with a RR of 30%; in CML in chronic phase the DFS is 60%, with a RR of 20%. These results have to be adjusted with other risk factors such as age, sex mismatch, disease status, CMV serology, and GVH. The use of donors different from a genotypically matched related donor is currently under investigation. Mismatched related transplants give disappointing results except in the case of one HLA mismatch. Unrelated HLA matched donor panels have been recently established in various countries with 200 transplants performed with a DFS of approximately 40%. Current research tries to reduce the risk of relapse by intensifying the conditioning or using the GVL effect of allogeneic T cells, to reduce GVH by the use of monoclonal antibodies and to improve the engraftment by the use of growth factors.
Cancer Detect Prev 1990
PMID:Recent trends in allogeneic bone marrow transplantation. 225 66

Fifty-six long-term survivors of bone marrow allografts were followed for a minimum of 40 months after bone marrow transplantation (BMT) to determine the frequency of secondary malignancies. The 56 patients included ten with severe aplastic anemia (SAA), 16 with acute myeloblastic leukemia (AML), 11 with acute lymphoblastic leukemia (ALL), and 19 with chronic myelogenous leukemia (CML). All patients received a preparative regimen combining high-dose chemotherapy with total body irradiation (TBI). Three patients developed a malignancy of the skin or oral mucosa. Two were diagnosed as squamous cell carcinoma and one as a malignant melanoma. All three patients had chronic graft versus host disease (GvHD) and were treated for prolonged periods with immunosuppressive medications. The lesions of all patients developed in areas involved by chronic GvHD.
Cancer 1990 Feb 01
PMID:Cutaneous and mucosal neoplasms in bone marrow transplant recipients. 229 38

CAMPATH-1M is a rat IgM monoclonal antibody which binds to an antigen on all human lymphocytes and monocytes, but which is not present on marrow stem cells (Hale et al., 1983). Lymphocytes can be efficiently killed in bone marrow buffy coat preparations using the antibody and donor human serum as a means to avoid graft versus host disease (GVHD) (Waldmann et al., 1984). An analysis of 520 matched sibling bone marrow transplants (BMT) for leukaemia demonstrates that T-cell depletion using CAMPATH-1M markedly reduces the incidence and severity of GVHD, but there is an increased risk of graft rejection. In the case of CGL in chronic phase, there is also an associated extra risk of relapse, particularly in patients where engraftment may have been compromised (Hale et al., 1988a). A rat IgG2b antibody of the same specificity as CAMPATH-1 (CAMPATH-1G) was developed which is able to both fix human complement and opsonize lymphocytes in vivo (Dyer et al., 1989). Initial studies for the prophylaxis of bone marrow rejection in 55 mismatched and matched unrelated donor (MUD) BMTs suggest that CAMPATH-1G treatment of the recipient may reduce, but not eliminate, marrow graft rejection. The broad CAMPATH-1 specificity means that it is also ideal for purging a range of lymphoid malignancies prior to autologous BMT, or even for direct serotherapy of leukaemic patients. However, there may be limitations of monoclonal antibody purging using complement or other natural effector mechanisms either in vivo or in vitro; in particular, antigenic modulation and an antiglobulin response. Phase 1 studies of "in vivo purging" with a monovalent CD3 antibody (Clark et al., 1989), and also with a genetically engineered humanized IgG1 (CAMPATH-1H) (Hale et al., 1988b) suggest that these limitations can be overcome.
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PMID:Purging in auto- and allografts: monoclonal antibodies which use human complement and other natural effector mechanisms. 230 78

Twenty-four patients were given the combination of methylprednisolone 100 mg i.v. on day 0, cyclosporine 2 mg/kg i.v. every 12 h starting on day -3 and methotrexate 5 mg/m2 on days 1, 3, and 6, then 10 mg/m2 on days 11 and 18 after allogeneic bone marrow transplantation for hematological malignancies for the prophylaxis of acute graft-versus-host disease. (GVHD). Methylprednisolone was given prior to the marrow infusion for its lympholytic effect. The methotrexate dose on days 1, 3, and 6 was half of that given in other studies to decrease the early toxicities. The outcome of this group is compared with patients transplanted before 1988 and given methotrexate alone, methotrexate with prednisone, or cyclosporine alone. There is no difference in relapse and survival between the groups at this time. The rate of engraftment and incidence of mucositis with the combination is not significantly different from the cyclosporine group. No patient developed greater than grade II acute GVHD with the combination. The probability of grade II or higher acute GVHD with the combination (14%) is significantly less than methotrexate, with or without prednisone or cyclosporine alone.
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PMID:Methylprednisolone, cyclosporine and methotrexate for prophylaxis of acute graft-versus-host disease. 233 38

Transient acanthosis nigricans (AN) was observed 3 months after bone marrow transplantation (BMT) for lymphoblastic lymphoma. The patient had no endocrine abnormality and had not received any drug known to induce AN. Forty-eight months post-BMT no malignancy recurred or appeared. Although usual hyperkeratosis, papillomatosis and acanthosis were present on skin biopsy, these were associated with the finding of keratinocyte necrosis and CD8+ lymphocytic infiltrate. It is suggested that graft-versus-host disease may be one of the triggers for AN.
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PMID:Transient acanthosis nigricans following bone marrow transplantation for lymphoid malignancy. 233 39

Twenty children with various hematological malignancies (nine with acute lymphoblastic leukemia, eight with acute non-lymphoblastic leukemia, two with chronic myelogenous leukemia, one with malignant lymphoma and one with 7-monosomy) and four with severe aplastic anemia were treated with allogeneic or syngeneic bone marrow transplantation (BMT) between September 1977 and September 1988. Eleven patients are surviving currently and ten are disease free 8 to 51 months after BMT. Conditioning regimen consisted of total body irradiation (TBI) and cyclophosphamide in twenty patients. Two patients did not receive TBI. Graft failure was observed in five patients and complete recovery of recipient marrow was seen in two of them. Eleven patients developed acute graft-versus-host disease (GvHD) with grade I-II in eight patients. Three patients suffered from chronic GvHD. Seven patients with acute leukemia relapsed and all but one died of leukemia. Early death occurred in two undergone BMT in poor clinical conditions. Performance status in 100% in surviving patients except one. Efforts to improve these results are that BMT should be considered early in the course of their disease for patients who are at risk for relapse with conventional chemotherapy and improved conditioning regimens to reduce leukemia relapse after BMT for patient with the second or subsequent remission.
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PMID:[Treatment results of bone marrow transplantation in Kyushu Cancer Center. Bone Marrow Transplantation Team]. 236 34

Bone marrow transplantation (BMT) is an increasingly effective treatment for patients with hematologic disorders and malignant neoplasms. From 1975 to 1986, 1,457 specimens were obtained for cytologic evaluation from 328 of the 635 patients who received BMTs at Memorial Sloan-Kettering Cancer Center. These specimens consisted of 1,049 cerebrospinal fluids (CSFs) from 265 patients, 292 bronchoscopy specimens from 92 symptomatic patients and 116 other specimens (including brushings from the liver and gastrointestinal tract, sputa, urines and cervico-vaginal smears). CSF specimens examined before and after BMT from 80 (30%) patients showed an increased number of benign, nonepithelial cells, which were mainly lymphocytic or histiocytic in origin. Malignant cells were detected in CSF specimens from 44 (17%) patients. Bronchoscopy specimens from 3 patients had suspicious cells present; those from 27 patients contained opportunistic organisms. Atypical epithelial or lymphoreticular cells were seen in bronchial specimens from 49 patients. All cytologic findings were correlated with the pertinent clinical information as well as biopsy and autopsy material, including histopathologic evidence of graft-versus-host disease. Cytologic evaluation, especially of bronchial and CSF specimens, was useful in diagnosing the presence of malignant neoplasms, infectious organisms, inflammatory responses, reactive lesions and cellular atypia due to treatment.
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PMID:The cytopathology of bone marrow transplantation. 237 25


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