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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)

Bone marrow transplantation (BMT) after supralethal cytoreductive therapy in the acute leukemias, chronic myelogenous leukemia (CML), and the lymphomas may be curative in 50% to 60% of patients. The donor may be a human leukocyte antigen (HLA) matched family member (allogeneic), an identical twin (syngeneic), or the patient (autologous). In general, the outcome is best in younger patients and those transplanted early in their disease (i.e., in the first remission for acute leukemia and in the chronic phase of the disease in CML). Solutions to the major problems of allogeneic BMT, such as graft-versus-host disease and viral infections, are being actively pursued. Syngeneic and autologous BMT avoids some of the above problems, but relapses appear to be greater. Despite this problem, a significant number of cures have been accomplished. Newer methods of purging autologous marrow and newer preparative regimens promise to reduce the problem of relapses.
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PMID:Bone marrow transplantation in hematologic malignancies. Current status. 240 2

Risk factors for graft failure were analyzed in 122 recipients of an allogeneic T-cell-depleted human leukocyte antigen (HLA)-identical sibling marrow transplant as treatment for leukemia. In each case pretransplant immunosuppression included 1,375 to 1,500 cGy hyperfractionated total body irradiation and cyclophosphamide (60 mg/kg/d x 2). No patient received immunosuppression prosttransplant for graft-versus-host disease (GVHD) prophylaxis. Nineteen patients in this group experienced graft failure. The major factors associated with graft failure were transplants from male donors and the age of the patient (or donor). Among male recipients of male donor-derived grafts a low dose per kilogram of nucleated cells, progenitor cells (colony forming unit-GM) and T cells was also associated with graft failure. Additional irradiation to 1,500 cGy, high dose corticosteroids posttransplant, and additional peripheral blood donor T cells did not decrease the incidence of graft failure. In addition, type of leukemia, time from diagnosis to transplant, an intact spleen, or the presence of antidonor leukocyte antibodies did not correlate with graft failure. To ensure engraftment of secondary transplants, further immunosuppression was necessary but was poorly tolerated. However, engraftment and survival could be achieved with an immunosuppressive regimen in which antithymocyte globulin and high dose methylprednisolone were administered both before and after infusions of secondary partially T-cell-depleted marrow grafts.
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PMID:Graft failure after T-cell-depleted human leukocyte antigen identical marrow transplants for leukemia: I. Analysis of risk factors and results of secondary transplants. 280 61

Japanese patients with leukemia who received bone marrow from human leukocyte antigen (HLA)-compatible siblings had a low incidence of acute graft-versus-host disease (GVHD). Twenty-five (21%) of 120 patients developed moderate (grade II) to severe (grades III to IV) acute GVHD. Severe GVHD was only seen in patients older than 20 years of age. It is also notable that only 2 (5%) of 39 patients who received the combination of methotrexate and cyclosporine (MTX/CSP) for the prevention of GVHD developed grade II acute GVHD, and none developed grades III to IV acute GVHD. Thirteen (30%) of 44 patients receiving MTX alone and 10 (27%) of 37 patients receiving CSP alone developed grades II to IV acute GVHD. Multivariate life-table analysis indicated that the prophylaxis by MTX/CSP was the risk factor for the low incidence of grades II to IV acute GVHD. Compared with the reported incidence of acute GVHD in the patients of the United States, lower incidence of acute GVHD in Japanese BMT patients might be attributable to a lesser degree of genetic diversity in histocompatibility antigens among Japanese.
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PMID:Low incidence of acute graft-versus-host disease by the administration of methotrexate and cyclosporine in Japanese leukemia patients after bone marrow transplantation from human leukocyte antigen compatible siblings; possible role of genetic homogeneity. The Nagoya Bone Marrow Transplantation Group. 280 62

Cyclosporin A (CyA) is the immunosuppressive treatment of choice in preventing allograft rejection and graft-versus-host disease. However, clinical trials indicate that there may exist inter-individual variations in sensitivity to the drug. We have approached this issue by studying CyA-mediated inhibition of in vitro alloreactions, as measured by mixed lymphocyte reactions (MLR) and cell-mediated lympholysis (CML), using mouse and human normal spleen cells. The differences between individuals in the CyA concentration required for 50% inhibition of the human alloreactions were twentyfold for the MLR and fortyfold for the CML. Moreover, the CML appeared to be inhibited at lower doses of the drug. No correlation was found between inhibitory doses and variables such as the magnitude of the response, age, or human leukocyte antigen phenotype. When the same experiments were performed with mouse spleen cells, no differences were observed among eight inbred strains. The lack of demonstrable individual sensitivity of mice in relation to humans is discussed.
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PMID:Inhibition of in vitro alloreactivity by cyclosporin A: evidence for an inter-individual variation in sensitivity. 293 52

This article compares the outcome of 14 patients with primary refractory acute leukemia who underwent bone marrow transplantation from human leukocyte antigen (HLA)-identical donors with that of 18 age-matched control patients who received chemotherapy. Complete clearing of leukemia was seen in all 14 transplanted patients. Five of the transplanted patients are alive 98 to 1790 days posttransplant, and four are free of leukemia. Nine patients have died, eight with severe graft-versus-host disease associated with interstitial pneumonia or systemic infections and one with relapse from chemotherapy-associated infections. Engraftment was seen in all patients. Severe graft-versus-host disease (grades III and IV) was seen in ten patients and resolved in three patients following high-dose corticosteroid treatment. Three of the 18 control patients are alive, none of them in complete remission. It appears that the combination of piperazinedione and total-body irradiation followed by allogeneic transplant is effective induction treatment for primary refractory acute leukemia and will be considered in the future as first salvage treatment for patients failing induction treatment.
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PMID:Allogeneic bone marrow transplantation for acute leukemia refractory to induction chemotherapy. 389 57

Bone marrow transplantation is now an accepted form of therapy for many hematologic disorders including aplastic anemia, genetically determined diseases and malignant diseases, particularly leukemia, and for rescue of patients given intensive chemoradiotherapy for malignant disease. The donor may be a healthy identical twin, a family member or even an unrelated person. Selection is made on the basis of human leukocyte antigen tissue typing. Intensive chemoradiotherapy is used to suppress patients' immune systems to facilitate engraftment and destroy diseased marrow. Transfusion of platelets, erythrocytes and granulocytes (or all of these), antibiotic coverage and protection from infection are necessary during the pancytopenic period. Use of a Hickman catheter facilitates maintenance of adequate nutritional intake and provides easy access for drawing blood and intravenous administration. Survival rates vary considerably depending on a patient's disease, clinical state and age. Patients with aplastic anemia transplanted early in the course of their disease have a survival rate of approximately 80%. Patients with acute lymphoblastic leukemia are usually transplanted in a second or subsequent remission and have a survival rate of 25% to 40%. Patients with acute nonlymphoblastic leukemia in remission have survivals ranging from 45% to 70%. More than 200 patients in the chronic phase of chronic granulocytic leukemia have been transplanted with survival ranging from 50% to 70%. Complications of marrow transplantation include marrow graft rejection, graft-versus-host disease, immunologic insufficiency and the possibility of recurrence of the leukemia. The risk of death from these complications must be balanced against the possibility of cure.
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PMID:Overview of marrow transplantation. 391 95

One hundred ten of 175 patients with aplastic anemia conditioned by cyclophosphamide had sustained engraftment of marrow from human leukocyte antigen (HLA)-identical siblings and lived for more than 6 months. Forty-nine of the 110 patients developed chronic graft-versus-host disease between 85 and 464 days. Ninety-seven patients are alive from 1.4 to 11 years after engraftment; 13 died between 208 and 726 days. Twenty of the 36 surviving patients with chronic graft-versus-host disease have Karnofsky performance scores of 100%, 7 of 90%, 5 of 80%, 1 of 70%, 2 of 60%, and 1 of 40%. Our analysis, using a binary logistic regression model, identified three factors predicting chronic graft-versus-host disease: moderate to severe acute graft-versus-host disease with an estimated relative risk of 11.65; increasing patient age; and the use of viable donor buffy coat cells in addition to the marrow to prevent graft rejection. The last two factors were significant only in patients without acute graft-versus-host disease.
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PMID:Predictive factors in chronic graft-versus-host disease in patients with aplastic anemia treated by marrow transplantation from HLA-identical siblings. 634 May 76

Intensive cytoreductive therapy may be curative in certain hematopoietic malignancies, but its administration is limited by lethal marrow toxicity. Bone marrow transplantation (BMT) provides a way of rescue from this toxicity. The donor may be a human leukocyte antigen (HLA) "matched" sibling (allogeneic), an identical twin (syngeneic), or the patient (autologous). Long remissions and possible cures of 50% to 60% have been reported in acute leukemia after intensive treatment with chemotherapy, with and without total body irradiation, followed by allogeneic BMT. A similar approach has been used in chronic myelocytic leukemia (CML) and in non-Hodgkin's lymphoma with encouraging results. Results are best in younger patients and those transplanted early in their disease (i.e., in the first remission for acute leukemia and in the chronic phase of the disease in CML). Solutions to major problems associated with allogeneic BMT, such as graft-versus-host disease and viral infections, are being actively pursued. Syngeneic BMT avoids some of the above problems, but relapses appear to be greater. Nevertheless, this approach has produced a significant number of cures. Autologous BMT is the newest approach, and the demonstration that marrow may be purged of residual tumor cells by immunologic or pharmacologic means has engendered enthusiasm for this area of clinical therapeutic investigation.
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PMID:Bone marrow transplantation in leukemia. Current status. 638 15

A 2-year-old boy who was receiving intensive chemotherapy for advanced neuroblastoma developed fatal graft versus host disease following administration of a unit of packed red blood cells from an unrelated donor. Graft versus host disease was documented by demonstrating human leukocyte antigen identity between the transfusion donor and the patient's peripheral circulating lymphocytes. Nonirradiated packed red blood cells contain viable lymphocytes and pose a risk to the immunosuppressed cancer patient.
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PMID:Fatal graft versus host disease following a blood transfusion in a child with neuroblastoma. 724 47

Minor histocompatibility antigen disparities between human leukocyte antigen (HLA)-matched bone marrow donors and recipients are a major risk factor for graft versus host disease (GVHD). An HLA-A2.1-restricted cytotoxic T cell clone that recognized the minor histocompatibility antigen HA-2 was previously isolated from a patient with severe GVHD after HLA-identical bone marrow transplantation. The HLA-A2.1-bound peptide representing HA-2 has now been identified. This peptide appears to originate from a member of the non-filament-forming class I myosin family. Because HA-2 has a phenotype frequency of 95 percent in the HLA-A2.1-positive population, it is a candidate for immunotherapeutic intervention in bone marrow transplantation.
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PMID:Identification of a graft versus host disease-associated human minor histocompatibility antigen. 753 51


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