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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) is an established therapy in pediatric oncology and is increasingly used as curative approach in the treatment of congenital, non-oncologic diseases of the lymphohematopoietic system. There is increasing evidence, however, that BMT can be followed by severe long term effects including neuroendocrine, ophthalmologic, dental and central nervous system abnormalities, particularly in children. Therefore the indication to BMT depends on the results obtained by conventional therapy. Due to the high cure rates of leukemia with conventional therapy BMT is only warranted following relapse except for certain forms with poor prognosis factors. For patients with chronic myelogeneous leukemia, however, BMT is the only chance of cure. In solid tumors the role of BMT is more difficult, because there is no clear evidence that BMT is superior to conventional therapy with regard to long term survival. In severe aplastic anemia, however, the long term results of BMT are clearly better than those obtained by conventional therapy. Other undisputed indications for BMT are severe combined immuno deficiencies and other congenital diseases for which BMT is currently the only curative therapy. Progress with matched unrelated donor transplantations by better histocompatibility testing and more specific immunosuppressive therapy to reduce graft-versus-host disease, still a major problem of allogeneic BMT, as well as the perspectives of gen therapy in the future will offer a chance of cure to many patients without a matched sibling donor.
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PMID:[Indications, problems and future perspectives of bone marrow transplantation in pediatrics]. 148 9

For treatment of steroid-resistant severe graft-versus-host disease, a murine monoclonal antibody (25.3) against the alpha chain (CD11a) of the lymphocyte function-associated antigen 1 (LFA-1) was infused into a patient with posthepatitic aplastic anemia who had undergone allogeneic bone marrow transplantation. The monoclonal antibody infusion was well tolerated and resulted in appreciable improvement in symptoms of gastrointestinal illness such as diarrhea and abdominal pain, suggesting that this antibody may be useful for controlling severe acute graft-versus-host disease.
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PMID:Anti-LFA-1 antibody treatment of a patient with steroid-resistant severe graft-versus-host disease. 148 52

A 16 year old boy underwent allogeneic bone marrow transplantation (BMT) from an human leukocyte antigen (HLA)-identical sibling for severe aplastic anaemia. He was symptomatic for 7 years before transplantation and had received multiple red blood cell and platelet transfusions. Conditioning for BMT consisted of cyclophosphamide, antilymphocyte globulin and total lymphoid irradiation. Engraftment was rapid, there was no evidence of rejection despite the history of multiple blood product transfusions and he did not develop acute or chronic graft versus host disease. He was well for the first 8 months after transplantation but then developed fevers, interstitial pneumonia, herpes simplex infections and cytomegalovirus enteritis. Serological studies revealed antibodies to human immunodeficiency virus (HIV) and he was considered to have acquired immune deficiency syndrome (AIDS). Retrospective analysis of the serum samples showed that he was seronegative for HIV until approximately 10 months before transplantation when his serum became HIV positive. Lymphocyte function studies done after transplantation suggested immunologic recovery at 3 months post-transplant with a brisk though subnormal response to phytohaemagglutinin stimulation. T cell subset analysis performed subsequently showed complete absence of CD4 positive cells indicating immune incompetence which was associated with clinical features of AIDS. Bone marrow transplantation had failed to produce sustained immunologic reconstitution and prevent the progression of HIV to which he ultimately succumbed.
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PMID:Failure of allogeneic bone marrow transplantation to benefit HIV infection. 149 64

Bone marrow transplantation from an HLA-identical sibling is increasingly used as a curative therapy for patients with hemopoietic stem cell disorders including acute leukemia, chronic myelogenous leukemia and severe aplastic anemia. Between March 1983 and March 1991, we performed 86 cases of allogeneic bone marrow transplantation (BMT) for the patients with hemopoietic stem cell disorders: 25 acute myelogenous leukemia (AML); 15 acute lymphoblastic leukemia (ALL); 20 chronic myelogenous leukemia (CML); and 26 severe aplastic anemia (SAA). Ten out of 25 AML are in disease free survival (DFS). The causes of death were recurrence of leukemia (12), acute GVHD (3), sepsis (1) and veno-occlusive disease (1). Nine of 15 ALL are in unmaintained remission. Thirteen out of 20 CML are in DFS. Among 26 SAA, 21 are enjoying DFS, but 1 died of engraftment failure, 3 of graft rejection followed by cytomegalovirus (1) and aspergillus pneumonia (1). Comparing the survival between standard [less than or equal to CR1: 9/14 (64%)] and high risk [greater than or equal to CR1: 1/11 (9%)] AML, our data suggest that preparative regimen for high risk AML was not potent enough to eradicate the minimal residual disease in advanced AML. Although our cases are limited and the follow-up period is short, our result of ALL [overall: CCR (60%), standard risk (adult less than or equal to CR1, children less than or equal to CR2; 8/11 (73%) and high risk; 1/4 (25%)] and CML [overall: 65%, CP; 9/10 (90%), AP; 4/6 (67%), BP; 0/4 (0%)] are optimistic. It is of our interest that the incidence of death related with IP (1/33: 3%) and with AGVHD 94/33: 12%) were much less than that of other's observation but the explanation for this still remains to be clear.
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PMID:Allogeneic bone marrow transplantation for the patients with hemopoietic stem cell disorders: CUMC experience. 151 32

Transfusion associated graft versus host disease is a rare disorder usually confined to patients who are immunosuppressed. A case is described in a 77 year old woman who was presumed immunocompetent. She was transfused with one unit of blood from an individual who was homozygous for the same HLA haplotype as her. The diagnosis of transfusion associated graft versus host disease should be suspected in a patient who develops aplastic anaemia within 30 days of a transfusion of blood products. It is suggested that blood donations from first degree relatives should not be permitted, unless the donation is irradiated to prevent lymphocyte proliferation.
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PMID:Transfusion associated graft versus host disease in an immunocompetent patient. 151 64

The presence of two distinct T-cell receptors (TCR) alpha/beta and gamma/delta dimers as well as of the activated T cells was analysed in peripheral blood mononuclear cells from seventeen recipients of allogeneic bone marrow transplants for leukemia and for severe aplastic anemia. Nine of seventeen recipients expressed an elevated percentage of T cells bearing TCR gamma/delta receptors in their peripheral blood. Seven out of nine cases having elevated gamma/delta positive cells showed chronic graft-versus-host (GVH) disease; one patient was treated with Cyclosporin A, and one patient was asymptomatic. In the twelve patients with GVH or other clinical symptoms, activated T cells (CD3+/HLA-DR+) were elevated indicating an autoreactive or alloreactive cell population. Our results confirmed earlier in vitro data showing that TCR-gamma/delta-bearing lymphocytes may be an activated T-cell population, and this T cell subset might be involved in mediating GVH disease, or in prolonging immunodeficiency after transplantation.
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PMID:TCR gamma/delta bearing lymphocytes in peripheral blood of allogenic bone marrow transplanted patients. 153 60

Nineteen patients with leukaemia, preleukaemia, and aplastic anaemia were treated by marrow transplantation from HLA-identical siblings. All were given postgrafting immunosuppression with a combination of methotrexate (days 1, 3, 6 and 11) and cyclosporin (days--1 to 180). In an attempt at reducing cyclosporin-associated toxicity, we explored whether the cyclosporin dose during the first 2 weeks could be decreased by 50% (from 3.0 to 1.5 mg/kg/d intravenously) without adversely affecting the incidence, onset, and severity of acute graft-versus-host disease (GVHD) and overall survival. Results from this pilot study were compared to those of a matched cohort of 38 patients given a standard dose of 3.0 mg cyclosporin/kg/d starting on day--1. The cumulative incidence of grade II and III acute GVHD in the 'low dose' cyclosporin group was 42% compared to 51% in the 'standard dose' group (P = 0.60). Three-year survival was 63% and 54% respectively (P = 0.59). Patients receiving the reduced cyclosporin dose during the first 14 d appeared to have less hepatotoxicity, and the methotrexate and cyclosporin doses administered were closer to the doses intended per protocol. We suggest that 'low dose' cyclosporin from day--1 to day 15 postgrafting might be as effective as 'standard dose' cyclosporin during that time period for the prevention of acute GVHD.
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PMID:A pilot study of low-dose cyclosporin for graft-versus-host prophylaxis in marrow transplantation. 153 9

A total of 21 multiply transfused patients with severe aplastic anemia (SAA) were treated with bone marrow transplantation between March 1985 and September 1990: 20 allogeneic and one syngeneic transplants. A positive response in mixed lymphocyte culture (MLC) was also noted in 7 allogeneic recipients. Pregraft conditioning included high-dose cyclophosphamide (CY) 200 mg/kg over 4 consecutive days, followed by 300 cGy total-body irradiation the day before BMT. Seventeen patients older than 14 years received additional donor buffy-coat cells infusion for 5 days posttransplant. A combination of methotrexate and cyclosporine was used for prophylaxis of graft-versus-host disease. Seventeen patients were alive with a functional graft, and Kaplan-Meier product limit estimates showed a 80.95% probability of survival at 67.7 months. There were 4 deaths: two died of primary graft failure, one from secondary rejection, and the other from chronic GVHD-related complications. Acute GVHD, grade I was noted in only one patient (5.6%). In contrast, chronic GVHD was observed in 10 out of 18 (55.6%) evaluable patients. Venoocclusive liver disease and interstitial pneumonitis were not diagnosed. Our findings indicate that the combination of CY/TBI/BC is well tolerated and results in a low incidence of graft failure/rejection in multiply transfused Chinese patients who received transplants for SAA. The MTX/CsA combination was confirmed as being remarkable in reducing the incidence and severity of acute GVHD. For patients with SAA under the age of 40, with an HLA-identical sibling, we highly recommend BMT as the treatment of choice.
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PMID:Bone marrow transplantation for severe aplastic anemia--a study of twenty-one Chinese patients in Taiwan. 154 48

Between 1971 and 1990, nine patients ranging in age from 14-38 years received marrow transplants for paroxysmal nocturnal hemoglobinuria (PNH). Six were transplanted for aplastic complications of PNH. Four of these were from HLA-identical siblings, and the patients were conditioned with cyclophosphamide. One graft was form a syngeneic twin without conditioning, and one from a two HLA-antigen nonidentical father after conditioning with cyclophosphamide and total body irradiation. Three of the four recipients of allogeneic marrow developed acute and two chronic graft-versus-host disease (GVHD). Five of six transplanted for severe aplastic anemia are long-term survivors with follow-up ranging from more than 6.2 to more than 19.1 years. The HLA nonidentical transplant recipient experienced graft rejection and died of a pulmonary hemorrhage. Three patients were transplanted for nonaplastic complications of PNH consisting of life threatening recurrent thromboses or refractory hemolysis. Two of these patients received marrow grafts from HLA-identical siblings after conditioning with busulfan and cyclophosphamide. They are surviving with normal hemograms greater than 2.2 and greater than 2.5 years and had mild chronic GVHD which resolved, although one has biochemical evidence of PNH in 15% of the red cells. One received a syngeneic marrow graft without conditioning but reverted to PNH. He is alive greater than 8.6 years after transplantation. Marrow transplantation for aplastic complications of PNH is successful, well tolerated, and compatible with long-term survival when an HLA-identical sibling or a syngeneic donor is available. For patients without aplasia, one must weigh the complications of transplantation with the life threatening nature of thrombotic episodes and hemolysis.
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PMID:Marrow transplantation for paroxysmal nocturnal hemoglobinuria. 155 57

Antithymocyte and antilymphocyte globulins (ALG) are currently used as immunosuppressive agents in organ transplantation and for the treatment of acute graft-versus-host disease and aplastic anemia. Since any type of immunosuppressive treatment is known to carry the risk of developing B-cell lymphoproliferative disorders, we investigated the in vitro effect of ALG on human B-cell activation and proliferation. The data demonstrate that whatever the source of lymphocytes used for ALG preparation (thymocytes, thoracic duct lymphocytes, B- or T-cell lines), (1) ALG react with both B- and T-cell lines, and (2) ALG contain antibodies specific for B cells (eg, CD21) or common to T and B cells (eg anti-beta 2-microglobulin, anti-HLA-DR, CD18, CD11a) in addition to T-cell-specific antibodies. Unlike all other T-cell mitogens tested (Concanavalin A [Con A], Pokeweek mitogen [PWM], CD3 and CD2 antibodies), ALG do not trigger B-cell differentiation into immunoglobulin-secreting cells at concentrations which induce maximum T-cell proliferation. This effect could be attributed to a direct interaction of ALG with B lymphocytes as shown by the capacity of ALG to block the response of purified B cells to a variety of activators. Furthermore, all the ALG tested were shown to inhibit the proliferation of six of the seven Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines and six of the seven Burkitt's lymphoma cell lines studied. This selective B-cell antiproliferative property of ALG was not reproduced with CD11a, CD18, CD21, CD24, or anti-HLA-DR monoclonal antibodies (MoAbs). These results suggest that, although suppressing T-cell responses, ALG treatment may directly control B cell proliferation to some extent, in keeping with the relatively low risk of posttransplant lymphoproliferative disorders reported with ALG.
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PMID:Antiproliferative effect of antilymphocyte globulins on B cells and B-cell lines. 156 43


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