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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)

An important contribution to the improved survival after bone marrow transplantation (BMT) over the past decade has been the development of strategies to prevent and manage infectious complications. Today, with these advances, deaths from bacterial and fungal infections are uncommon except in the setting of uncontrolled graft-versus-host disease (GVHD) or failure of engraftment. Historically, the major life-threatening pathogens have been viruses, especially the herpesvirus family. However, they too have become less deadly with the introduction of antiviral agents, changes in transfusion strategies, improvements in the control of GVHD, and better diagnostic procedures. With improved detection methods, we now recognize that some complications formerly thought to be due to treatment toxicities are caused by infectious pathogens. We are increasingly recognizing the complex interplay between immunodeficiency, tissue damage, infectious pathogens, and disordered immune responses. This greater knowledge in time should improve our understanding of the biology of BMT as well as result in improved outcomes.
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PMID:Advances in the management of infectious complications after bone marrow transplantation. 795 Nov 11

Secondary lymphoproliferative syndromes in immunosuppressed patients have been characterized as polyclonal or monoclonal B-lineage disorders nearly always associated with Epstein-Barr virus (EBV) infection. The authors now report three patients with a distinctly different lymphoproliferative syndrome. Two patients with common acute lymphoblastic leukemia antigen (CALLA) (CD10)-positive acute lymphoblastic leukemia and one patient with acute myelogenous leukemia, respectively, received high-dose chemoradiotherapy followed by marrow transplantation from either an HLA-identical sibling or HLA-mismatched parent. All three patients developed severe graft-versus-host disease (GVHD), requiring immunosuppressive treatment with corticosteroids. A secondary malignant T-cell lymphoproliferation occurred 2, 21, and 43 months, respectively, after marrow transplantation. In all three cases the lymphoid cells expressed T-cell surface antigens and were morphologically and immunophenotypically distinct from the malignant cells present before transplantation. One tumor was of host cell origin, one was probably of donor origin, and the tumor origin in the third case could not be determined. The authors were unable to find any evidence for EBV, human T-cell lymphotropic virus type I or II, human immunodeficiency virus, or human herpesvirus 6.
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PMID:Secondary T-cell lymphoproliferation after marrow transplantation. 217 84

Fourteen patients with T-cell-derived leukemia and lymphoma underwent high-dose chemoradiotherapy and anti-T-cell monoclonal antibody-treated autologous bone marrow transplantation (ABMT). All patients were either in sensitive relapse or had adverse prognostic features, and five patients had a history of bone marrow involvement with disease. Patients received a median of 2 (1 to 3) prior chemotherapy regimens; 10 patients received local radiotherapy. After high-dose ablative therapy, greater than 500/mm3 granulocytes and greater than 20,000 untransfused platelets/mm3 were noted at a median of 23 (13 to 48) and 26 (15 to 43) days post-ABMT, respectively. Natural killer (NK) cells, T cells (predominantly T8+), and monocytes were noted within the first 1 to 2 months post-AMBT, as seen in other series. Disease-free survival was a median of 10.1 months, 5.9 months for patients with T acute lymphoblastic leukemia or lymphoblastic lymphoma and 25.6 months for patients with T non-Hodgkin's lymphoma (NHL). Toxicities were common and severe. Thirty-six percent of patients developed bacteremias early post-BMT. Late complications included a skin rash consistent with graft versus host disease; infections with Herpes zoster, hepatitis, and Pneumocystis carinii; and the development of Epstein-Barr virus associated lymphoproliferative syndrome. Our findings suggest that patients who have undergone T-depleted ABMT have a profound immunodeficiency not reflected in the phenotypic reconstitution of the T and NK cells. Characterization of the functional deficiency may facilitate the development of methods to reduce the long-term toxicity of AMBT in these patients.
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PMID:T-cell-depleted autologous bone marrow transplantation therapy: analysis of immune deficiency and late complications. 219 91

Fatal graft versus host disease (GVHD) developed in a child with purine nucleoside phosphorylase (PNP) deficiency following an unirradiated platelet transfusion. IV treatment with an anti-T-cell monoclonal antibody (CD7) led to a transient improvement of his GVHD (Grade IV) but did not prevent the fatal outcome. This report emphasizes the need for blood products to be irradiated when cell mediated immunodeficiency is suspected, even in patients with residual immunocompetence.
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PMID:Fatal graft versus host disease after platelet transfusions in a child with purine nucleoside phosphorylase deficiency. 249 62

Six cases of post-operative erythroderma after open heart surgery are described. About 10 days after seemingly uneventful recovery, all patients developed fever, erythroderma, liver enzyme elevation, pancytopenia, and an aplastic bone marrow. Their condition rapidly deteriorated, and they died within 20 days of the onset of symptoms. Skin biopsy specimens from two patients showed mild leukocytic infiltration in the epidermal basal layer and upper dermis. Immunostaining by the ABC method showed that most of these infiltrating cells were suppressor/cytotoxic T cells. HLA study of peripheral lymphocytes from two patients and their families revealed that the patients' HLA phenotypes were incompatible from their children's HLA findings. Y chromatin was present in the lymphocytes of the skin biopsy specimen of a female patient. Based on the clinical picture, skin biopsy, HLA study, and Y chromatin study, the authors strongly suspect post-transfusion GVHD as the etiology of postoperative erythroderma, although these patients lacked any known immunodeficiency.
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PMID:Post-transfusion graft-versus-host disease following open heart surgery. Report of six cases. 252 50

An increasing number of diseases may be treated successfully by allogeneic bone marrow transplantation (BMT). Initially used for the treatment of immunodeficiency where a cell series or product is replaced, it has now become routine treatment for many forms of leukemia where the transplant provides the rescue after lethal marrow ablation. Recently, diseases such as thalassemia and other inherited metabolic diseases have also been treated by BMT. Formerly the problems of BMT were mainly concerned with graft versus host disease (GVHD) in HLA-matched transplants with HLA-mismatched ones not being possible as GVHD was usually fatal. Since the development of techniques for T cell removal the incidence of GVHD has greatly diminished. T cell removal has also allowed HLA haploidentical mismatched grafts to be performed successfully for immunodeficiency, but there is still a high graft rejection rate in leukemia. This also occurs to a lesser extent with HLA-matched grafts in leukemia. Furthermore, in certain forms of leukemia, particularly chronic granulocytic leukemia, the relapse rate after T cell-depleted BMT is much higher. Trials of better forms of bone marrow conditioning of the recipient are being attempted in order to prevent graft rejection and leukemia relapse. These include total lymphoid irradiation, heavier irradiation and chemotherapeutic regimens, or the use of in vivo monoclonal antibodies such as CAMPATH 1G or anti-LFA-1 (CD11a). In the future, positive selection of stem cells combined with hemopoietic growth factors may allow engraftment without graft versus host disease. This should become the method of choice for autologous transplantation for malignancy. Two monoclonal antibodies directed against the human progenitor cell antigen 1 (HPCA-1) (CD34) have been used for autologous positive stem cell selection in primates and these cells gave full hemopoietic reconstitution in the animals following lethal total body irradiation.
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PMID:Recent advances in bone marrow transplantation. 256 39

The survey of the characteristics of HIV infection implicates the binding of HIV env to the CD4 receptor as the principal cause of the resulting immunodeficiency. There is evidence that such binding selectively impairs self-recognition. The resulting immunodeficiency syndrome has the characteristics of graft vs. host disease, consistent with chronic allogeneic and semiallogeneic GVHD in mouse-models. since these syndromes are believed to result from triggering the established immunoregulatory mechanisms necessary to maintain self-tolerance, vaccination to prevent AIDS should aim to correct the inability of the HIV host mount an immune response against CD4 binding epitopes on HIV gp120, preferably without exposing the vaccine to intact envelope glycoprotein. Since the AIDS syndrome is probably a defect in net-work immunoregulation, the most appropriate target for therapy and for vaccination is the idiotype of anti-CD4 antibodies that block CD4/env interaction.
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PMID:The relevance of HIV env/CD4 interactions to the pathogenesis of acquired immune deficiency syndrome. 267 11

Jejunal biopsy specimens from 20 human immunodeficiency virus (HIV) positive male homosexual patients were analysed and compared with those of a control group to determine whether the abnormalities were caused by the virus or by opportunistic infection. The degree of villous atrophy was estimated with a Weibel eyepiece graticule, and this correlated strongly with the degree of crypt hyperplasia, which was assessed by deriving the mean number of enterocytes in the crypts. The density of villous intraepithelial lymphocytes fell largely within the normal range, either when expressed in relation to the number of villous enterocytes or in relation to the length of muscularis mucosae. Villous enterocytes showed mild non-specific abnormalities. Pathogens were sought in biopsy sections and in faeces. Crypt hyperplastic villous atrophy occurred at all clinical stages of HIV disease and in the absence of detectable enteropathogens. An analogy was drawn between HIV enteropathy and the small bowel changes seen in experimental graft-versus-host disease. It is suggested that the pathogenesis of villous atrophy is similar in the two states, the damage to the jejunal mucosa in HIV enteropathy being inflicted by an immune reaction mounted in the lamina propria against cells infected with HIV.
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PMID:Jejunal enteropathy associated with human immunodeficiency virus infection: quantitative histology. 270 44

Allogeneic bone marrow transplantation can cure a substantial proportion of patients with hematologic malignancies. However, graft versus host disease (GvHD) and a sometimes long lasting immunodeficiency are the major obstacles to an improved survival rate. Passive immunization is a prophylactic and therapeutic approach increasingly considered in these patients and the question as to whether or not this expensive treatment is efficacious needs thorough evaluation. Several studies have been completed using either polyvalent immunoglobulins or CMV-hyperimmunoglobulin to prevent fatal CMV pneumonia posttransplant. Most studies did show a decreased mortality from this complication when immunoglobulins were given at higher doses in weekly intervals. Studies are also underway to evaluate, if the incidence of GvHD can be decreased by immunoglobulins, since it is known that infections can trigger the clinical manifestation of this complication. It is too early to say if bacterial and fungal infections after engraftment can be diminished specifically in patients at risk for infectious complication such as those with chronic GvHD. A hyperimmunoglobulin against varicella zoster is recommended in case a transplant patient has been exposed to varicella. It can also be given as an additive measure in severe disseminated varicella infections. Hyperimmunoglobulins against pseudomonas aeruginosa are currently being studied in humans and it is too early to decide whether or not they have a positive impact on patient survival.
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PMID:[Is the administration of immunoglobulins following bone marrow transplantation indicated?]. 282 97

Following ablative treatment with supralethal doses of chemotherapy and total body irradiation, patients demonstrate multiple immunologic deficiencies after bone marrow transplantation. Immune function usually recovers and the risk of infection decreases within six to 12 months. However, patients in whom chronic graft-versus-host disease (GVHD) develops have persisting B and T cell abnormalities, and in vivo and in vitro studies show impaired immunoglobulin regulation and function despite normal levels of serum immunoglobulin G. This review summarizes 12 published clinical trials of immunoglobulin therapy to correct immunodeficiency and prevent infection after marrow grafting. In five controlled studies, cytomegalovirus infection developed in a total of 52 of 172 (30 percent) immunoglobulin recipients and 71 of 165 (43 percent) control patients not given globulin. In four controlled trials, interstitial pneumonia developed in a total of 21 of 127 (17 percent) immunoglobulin recipients and 40 of 94 (43 percent) control patients. Three randomized trials reported a reduced rate of GVHD or post-engraftment septicemia in immunoglobulin recipients. However, methods of immunoglobulin preparation, antibody titer, and dose and schedule of prophylaxis varied widely in these studies, as did other critical patient, transplant regimen, and supportive care factors. Accordingly, data should be interpreted with caution. Ongoing controlled clinical trials will further define the proper role of immunoglobulin therapy in bone marrow transplantation.
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PMID:Immunoglobulin therapy in bone marrow transplantation. 282 2


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