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)

Gliotoxin, a secondary fungal metabolite, at nanomolar concentrations, irreversibly inhibits murine T cell proliferation to mitogen. Treatment of allogeneic spleen cells with gliotoxin allows their transfer into sublethally irradiated recipients without inducing a GVH reaction. Gliotoxin treatment of bone marrow allows the establishment of fully allogenic bone marrow chimeras free of GVH disease. The cytotoxic T cell repertoire against influenza virus in these animals is restricted to both host- and donor-type MHC. However, their immune competence is severely compromised by their lack of host MHC-type stimulator cells.
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PMID:Prevention of graft-versus-host disease by treatment of bone marrow with gliotoxin in fully allogeneic chimeras and their cytotoxic T cell repertoire. 245 43

Allogeneic bone marrow transplant patients are severely immunocompromised during the immediate posttransplant period, and the risk for common and opportunistic infections may persist for many months. The role of reimmunization for these patients, however, remains unsettled. We briefly review current concepts regarding the recapitulation of immunity from the totipotential hematopoietic stem cells in the donor marrow. The fact that various components of the new immune system mature at different rates can have clinical consequences with regard to specific infections. Most previously immunized patients become antibody seronegative within a few months after allogeneic marrow transplantation. Adoptive transfer of specific antibody-producing cells from the donor to the recipient has been demonstrated in small clinical trials, and is augmented when both donor and recipient are vaccinated. Passive transfer of immunity is more easily achieved to recall antigens than to neoantigens. Primary immunization requires prolonged antigenic stimulation and mature T-cell function or help from natural killer cells. Most healthy patients generate adequate antibody titers to vaccinations that are given 12 months after transplantation, but the presence of chronic graft-versus-host disease can diminish the response. Currently available vaccines have been evaluated in marrow transplant patients. Protein antigens such as tetanus and diphtheria toxoids are more immunogenic than polysaccharide antigens such as pneumococcal vaccine. The new polysaccharide-protein conjugate vaccines, such as the Hemophilus influenzae type b vaccine, also appear more immunogenic. Inactivated poliovirus vaccine has been used successfully. Relatively few data are available about hepatitis B or influenza vaccines. The literature supports the use of standard vaccines in allogeneic bone marrow transplant patients. However, more data on the optimal methods and timing of immunization are needed. We present guidelines for a reimmunization schedule.
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PMID:Reimmunization after allogeneic bone marrow transplantation. 770 53

The major topics covered at this conference included the relevance of the SIV-macaque model for HIV vaccine development, an evaluation of the methods for producing inactivated vaccine, and the possibility of developing attenuated retrovirus vaccines. The possibility that there might be a Graft Versus Host Disease component in human AIDS was discussed, and also the recent discovery that the 'original antigenic sin' phenomenon encountered in influenza vaccines may also be seen in AIDS. It was concluded that results from animal models were encouraging in the quest for an HIV-1 vaccine.
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PMID:Challenges and strategies for AIDS vaccine development. 810 Jun 64

Immunocompromised patients with influenza A were identified in Stockholm during two influenza seasons. The predominant subtypes were H3N2 during 1988-1989 and H1N1 during 1990-1991. The median age of the 25 patients was 43 years (range, 3-80 years). Twelve patients had received renal transplants and had ongoing immunosuppression. Seven patients had received bone marrow transplants between 2 days and 3 years before becoming infected with influenza virus A. Two patients were in an aplastic phase, and four had chronic graft-versus-host disease with ongoing immunosuppression. Six patients had hematologic malignancies. Two of the 25 patients had severe infections. One of these infections occurred in a bone marrow transplant recipient during an aplastic phase and was fatal; the other affected a patient who had received a renal transplant. One bone marrow transplant patient had mild but protracted infection. The remaining 22 patients had mild influenza A. We conclude that influenza A in immunocompromised patients occasionally causes severe complications but in most patients is mild and self-limiting.
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PMID:Influenza A in immunocompromised patients. 839 75

Induction of protective hemagglutination-inhibition (HI) antibodies in response to influenza virus vaccine and the effectiveness of two doses versus a single dose of vaccine were studied in 48 BMT recipients. The patients were 1-50 years old (median 21 years), 33 with malignant and 15 with non-malignant disease. Thirty-five of the patients underwent allogeneic, T lymphocyte-depleted, BMT and 13, autologous BMT. Nine patients had GVHD at initial immunization. The time interval from BMT to influenza vaccination ranged from 2 to 82 months (median 14.5 months). Two doses of vaccine, administered 1 month apart, consisted of trivalent influenza subunit inactivated vaccine with the following strains: A/Singapore/6/86 (H1N1), A/Sichuan/2/87 (H3N2), and B/Beijing/1/87. There was a statistically significant association between development of protective antibody level (> or = 1:40) and the time interval between BMT and initial vaccination (p < or = 0.001). Regression analysis revealed that longer time interval between the BMT and immunization was positively correlated with seroconversion (a fourfold or greater rise in titers). In the presence of GVHD, there was reduced seroconversion to H1N1, but not to H3N2 or B strains. Influenza vaccination within the first 6 months following BMT was totally ineffective. The efficacy of the vaccine was similar to that described in non-immunocompromised hosts initiated 2 years following BMT. As, overall, specific response was only marginally enhanced by the second dose of vaccine, its indication is questionable.
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PMID:Antibody response to a two-dose regimen of influenza vaccine in allogeneic T cell-depleted and autologous BMT recipients. 843 6

Recent findings indicate that the kinetics of B-cell reconstitution after marrow transplantation mimic normal ontogeny. The early B-cell repertoire during ontogeny is characterized by a high degree of autoreactivity and interconnectivity. Therefore, in a prospective analysis, 95 consecutive recipients of an allogeneic marrow transplant were screened for the occurrence of various autoantibodies and 47 of these 95 were also screened for monoclonal gammopathies. None of the patients developed antibodies specific for systemic autoimmune disorders. In contrast, a high prevalence of natural antibodies (79/95) was found early post-transplant, with 58 of these 79 patients developing two or more autoantibodies. According to multiple regression, the mean number of natural antibodies (95% confidence limits in parentheses) depends significantly (P = 0.006) on the status of CMV infection: 0.9 (0.4; 1.6) CMV-negative: 2.0 (1.0; 3.3) asymptomatic CMV infection; 3.1 (1.7; 5.0) CMV disease. Sex, age, underlying disease, conditioning therapy, acute graft-versus-host disease and CMV serology of donor and recipient pretransplant did not affect the number of natural autoantibodies. Monoclonal gammopathies were detected in 12/47 patients with a predominance of the IgG-kappa subtype. All these 12 patients suffered from a viral infection (CMV, n = 11: influenza strain A, n = 1). The high degree of self-reactivity post-transplant further supports the hypothesis that B-cell reconstitution mimics ontogeny. Moreover, these data indicate nonspecific polyclonal, CMV-mediated, presumably T-cell independent B-cell stimulation and disturbed T-cell regulatory function following allogeneic BMT.
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PMID:CMV infection after allogeneic bone marrow transplantation is associated with the occurrence of various autoantibodies and monoclonal gammopathies. 885 52

Bone marrow transplant recipients remain at risk for infections for a variable period of time even after adequate hematologic reconstitution. Late infections are a significant cause of morbidity and can be fatal in 4-15% of these patients. Patients with chronic graft versus host disease (GVHD) and unrelated-donor transplant recipients, even without GVHD, are at particular risk. Most late infections occur in the first post-transplant year, the majority are caused by bacteria, particularly encapsulated organisms, or herpes group viruses (CMV and VZV) and present with cutaneous, sino-pulmonary or systemic involvement. Effective chemoprophylaxis is available only for the encapsulated bacteria (penicillin or erythromycin) and Pneumocystis carinii (trimethoprimsulfamethoxazole). Routine use of long-term I.V. immunoglobulin supplementation has not been shown to be effective and may be harmful as it may delay reconstitution of humoral immunity. Active immunization (pneumococcal vaccine, influenza vaccine and HiB) can be effective in patients more than 6-12 months from transplant who do not have GVHD. In this review we present our experience, a summary of published literature on the subject of late infections in bone marrow transplant patients and offer guidelines for preventative strategies.
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PMID:Late infections following allogeneic bone marrow transplantation: suggested strategies for prophylaxis. 925 Jul 82

Viral infections are important in SCT patients. Different viruses are challenges for the physician at different times after transplantation due to changing defects in the immune status of the patients. Infections with respiratory viruses in particular respiratory syncytial virus are important early after transplant but the knowledge about epidemiology, risk factors, and treatment is still limited. Parainfluenza and influenza viruses can also cause severe and sometimes fatal infections after SCT. During the acute GVHD phase, CMV has been the most important viral infection during the entire history of allogeneic SCT. Recent developments with antiviral prophylaxis, new techniques for early diagnosis, and the strategy of preemptive antiviral therapy has reduced its importance in matched sibling transplants. Instead CMV disease occurring late after SCT has become an increasingly important problem in patients who have undergone unrelated or mis-matched SCT due to poor development of T-cell function. Other herpesviruses such as human herpesvirus type 6 and EBV are also becoming important causes of severe complications after unrelated and mismatched SCT. For this group of patients new innovative preventive and therapeutic strategies are needed.
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PMID:Immune reconstitution and viral infections after stem cell transplantation. 963 Mar 32

Allogeneic bone marrow transplantation (BMT) causes a beneficial graft-versus-tumor (GVT) immune response that is often associated with graft-versus-host disease (GVHD). There is substantial interest in developing therapeutic strategies that augment GVT without GVHD. We have demonstrated recently that immunization of BMT donors with cellular tumor vaccines leads to curative GVT but induces unacceptable GVHD because of the presence of recipient minor histocompatibility antigens (mHAgs) in whole-cell tumor vaccines. This study tested the hypothesis that immunization of BMT donors against a defined tumor-specific antigen with a vaccine not containing recipient mHAgs would help to separate the two responses by enhancing GVT activity without exacerbating GVHD, even when cellular vaccines were used after BMT. Recipient strain C57BL/6 fibrosarcoma cells engineered to express the well-characterized model tumor antigen, influenza nucleoprotein (NP), were used in these studies. C3H.SW donors were immunized against NP prior to BMT, and cytolytic T cells were transferred along with bone marrow into irradiated H-2-matched, mHAg-mismatched C57BL/6 recipients with established micrometastatic 205-NP tumors. Donor immunization led to a significant increase in GVT activity, as measured by reduction in tumor growth and enhanced survival. However, deaths in recipients of tumor antigen-specific immune BMT ultimately occurred because of the growth of antigen-loss variants; such tumor growth did not occur in animals receiving BMT from donors treated with whole-cell vaccines. Donor immunization did not lead to an exacerbation of GVHD, even when BMT recipients received additional immunization after BMT with a 205-NP "whole" tumor cell vaccine (which was shown to induce fatal GVHD when used for donor immunization). In conclusion, immunization of allogeneic BMT donors against a tumor-specific antigen significantly enhances GVT activity without an associated exacerbation of GVHD.
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PMID:Pretransplant tumor antigen-specific immunization of allogeneic bone marrow transplant donors enhances graft-versus-tumor activity without exacerbation of graft-versus-host disease. 1105 76

Functional hyposplenia/asplenia is a severe longterm complication after allogeneic stemcell transplantation predominantly seen in patients who suffer from extensive chronic graft versus host disease (cGvHD). The risk of acquiring an overwhelming infection with encapsulated bacteria is ca. four fold increased in patients with functional hyposplenia/asplenia. Therefore follow up of patients who have received allogeneic blood stem cells (bone marrow or peripheral blood stem cells) should embrace screening for functional hyposplenia. When functional hyposplenia is diagnosed triple vaccination against streptococcus pneumonia, Haemophilus influenza type B and Meningococcus neisseria should be considered. Goldstandard in diagnosing functional hyposplenia is hepatosplenic scintigraphy. We present the case of 37 year old female in whom sonography was indicative of functional hyposplenia. The diagnosis was confirmed by scintigraphy. Sonography including color coded duplex sonography is a safe and cost saving procedure. Sensitivity, Specificity and predictive value of the following sonographic finding: a) decreasing splenic size and b) diminished or absent parenchymal blood flow are currently evaluated in a prospective study.
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PMID:[Functional hyposplenia after allogenic bone marrow transplantation: a case report]. 1174 Jun 98


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