Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In addition to our center (Northwestern University, Chicago), several institutions in the United States (Fred Hutchinson Cancer Center, University of California at Los Angeles, and Medical College of Wisconsin) and Europe are activating protocols to transplant patients with SADS. In this age of cost-effectiveness, it will be difficult to arrange third-party reimbursement for a hematopoietic stem cell transplant that may lead to medical charges of between $100,000 and $200,000. However, the cost of standard medical care for patients with SADS is not trivial. Dialysis for an SLE patient with renal failure costs $40,000 per year, while the medical resources required to care for a patient with progressive multiple sclerosis may exceed $35,000 per year. Unique BMT regimen-related toxicities may occur, including intracranial hemorrhage in the SLE or rheumatoid arthritis patient who has vasculitis; acute neurologic decompensation in patients with multiple sclerosis, especially if the conditioning regimen contains neurotoxic agents that cross a compromised blood-brain barrier; respiratory failure in patients with myasthenia gravis; and increased renal or pulmonary toxicity in patients with scleroderma and parenchymal fibrosis. Scleroderma-associated gastrointestinal dysmotility and bacterial overgrowth may also lead to greater fungal and bacterial infections [76]. BMT is currently considered appropriate therapy for patients with chronic-phase Chronic myelogenous leukemia (CML) and indolent lymphomas who otherwise have a relatively long life expectancy of 5 and 10 years, respectively. The roughly similar long survival but greater functional impairment of patients with SADS may justify consideration of immune ablation and hematopoietic stem cell rescue.
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PMID:Immune ablation and hematopoietic stem cell rescue for severe autoimmune diseases (SADS). 907 9

A 26-year-old man, affected by acute non-lymphocytic leukemia, received a bone marrow transplantation from his HLA identical sister. A mild (grade 1) acute graft-versus-host disease (GVHD) developed during the first month after BMT. A moderate (grade 2) muco-cutaneous GVHD was present from the 4th month on, in association with recurrent oral herpes simplex infection. A typical clinical and electromyographic picture of myasthenia gravis (MG) developed 46 months after BMT, requiring continuous medication with pyridostigmine. A high titer of antibiotics against the acetylcholine receptor was found in the serum of the patient but not in the serum of the donor. Since the donor had no evidence of MG or other autoimmune disorders, this is likely to be an autoimmune complication of chronic GVHD. Other cases described in the literature are reviewed: a recurrent expression or coexpression of some HLA antigens was recorded, indicating that some genetic factors could predispose to this acquired disorder.
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PMID:Myasthenia gravis after allogeneic bone marrow transplantation. A case report and a review of the literature. 932 79

Since Morton and Siegel's epochal experiments 30 years ago animal models have been successfully utilized both for transfer and resolution of autoimmune diseases (AID). More recently human lymphocyte xenografts have reproduced clinical AID in SCID mice. Allogeneic stem cell transplantation demonstrated therapeutic potential in fully developed autoimmune disease. Mixed allogeneic chimerism induced by a sublethal approach has also been shown to prevent and even reverse autoimmune insulitis in nonobese diabetic (NOD) mice. More unexpectedly it was found that experimental adjuvant arthritis (AA) and experimental allergic encephalomyelitis (EAE) could be cured by means of total body irradiation (TBI) followed by autologous hemolymphopoietic stem cell (HSC) transplantation. It was postulated that the newly developing T cells might be tolerant to self antigens. The transfer of AID from affected donors to recipients of allogeneic HSC transplants has been reported for many organ-specific AID, including diabetes (IDDM), thyroiditis, myasthenia gravis and thrombocytopenic purpura (AITP); rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were not transferred. Conversely patients with the combination of AID and a severe blood disease (leukemia, aplasia) were cured of both diseases following allogeneic BMT, with the notable exception of a relapse in a patient with RA despite full donor engraftment. Allogeneic transplants are certainly more promising as far as concerns a resolution of AID, because they may also exert a graft-versus-autoimmunity effect by gradually eradicating the recipient's lymphopoiesis, but transplant related mortality (TRM) is considered still too high to employ this procedure consistently. New non-myeloablative conditioning regimens, designed to allow the donor's immune system to take over, are already utilized for malignant and non-malignant hematologic diseases, and may become an attractive option for severe, refractory AID. For the time being, however, autologous procedures are still safer, and are being utilized in many projects worldwide. The EBMT/EULAR Registry has collected over 70 patient reports. The more numerous and favorable results have been obtained up to now in multiple scleosis and in systemic lupus erythematosus; the worst in refractory autoimmune thrombocytopenic purpura. No definite conclusions as to the efficacy of autologous HSC transplantation, from marrow or from blood, with or without T-cell depletion, may be drawn at this time, but the feeling is that real cures will be very difficult to obtain by this approach, and that corticosteroid-free remissions and a general lowering of the autoimmune potential will be more realistic goals. Accurate comparisons with already existing aggressive immunosuppressive protocols will become necessary, if possible by means of prospective randomized clinical studies.
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PMID:Stem cell transplantation for severe autoimmune diseases: progress and problems. 979 58

BMT can both transmit and eliminate autoimmune diseases, and hence it has been suggested as an optional treatment for severe autoimmune conditions. In this communication we deal with the question of whether chronic GVHD is an autoimmune disease in itself, review the literature reports of autoimmune diseases following BMT in humans, and describe the autoimmune nature of the post-BMT state. Chronic GVHD, which is a frequent complication post-BMT, has clinical and pathogenic characteristics similar to autoimmune diseases, such as scleroderma and Sjogren's syndrome. Although the pathogenesis of chronic GVHD is not yet clear, thymic damage induced by acute GVHD may contribute to both the immunodeficiency and autoimmunity characterising chronic GVHD. A similar phenomenon is syngeneic GVHD, which results from an imbalance between autoreactive and autoregulatory lymphocytes. Additionally, other autoimmune diseases have been reported in post-BMT patients, and among these the most common are hypothyroidism, hyperthyroidism, myasthenia gravis and immune cytopenias. Although these diseases also occur also outside the post-BMT setting, they are unique with respect to pathogenesis (no association between myasthenia gravis and thymic pathology), diagnosis (symptoms of hyperthyroidism may be inadvertently related to other conditions), and prognosis (post-BMT autoimmune cytopenias may be fatal and treatment non-responsive). Nevertheless, many other autoimmune diseases have been reported after BMT, and these are mainly presented as case reports. Regarding the mechanism of post-BMT autoimmunity, the minority of cases stem from donor-related transfer of pathogenic lymphocytes or their progenitors, while most of the cases (either chronic GVHD or specific diseases) can be attributed to the immunologic imbalances characterising the post-BMT setting. The factors that may expose an individual to autoimmunity development post-BMT include genetic predisposition, an environmental factor such as CMV, and the nature of the donor who may aid in creating microchimerism and subsequently chronic GVHD and its related autoimmune manifestations.
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PMID:Autoimmune diseases and autoimmunity post-bone marrow transplantation. 982 15

Myasthenia gravis and polymyositis are each a rare manifestation of immune dysregulation in chronic graft-versus-host disease (cGVHD). We report a 4-year-old boy with idiopathic acquired aplastic anemia who developed myasthenia gravis 22 months and polymyositis 69 months after an allogeneic BMT (5/6 matched, MLC-nonreactive). The occurrence of both syndromes in one patient is unique. Autoimmune dysfunction may be associated with the development of cGVHD as demonstrated by the high incidence of prior aplastic anemia in BMT patients presenting with myasthenia gravis and polymyositis. Recognition of these neurologic manifestations is important in the diagnosis and treatment of cGVHD.
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PMID:Myasthenia gravis and polymyositis as manifestations of chronic graft-versus-host-disease. 1010 May 85

Experimental autoimmune myasthenia gravis (EAMG) can be induced in a large number of animal species by active immunization (AI) AChR, by passive transfer (PT) of anti-AChR antibodies, by autologous bone marrow transplantation and cyclosporin (BMT-Cy), or spontaneously. Depending on the model used, different immunological mechanisms are operational. In the AI model, the T cell is pivotal in directing the anti-AChR antibody production towards pathogenic, that is, cross-linking and complement-fixing antibodies. Injection of anti-AChR antibodies alone suffices to induce EAMG, excluding the role of specific cell-mediated immune responses in the effector phase of the disease. Aged animals are resistant to the induction of AI and PT EAMG. This resistance is localized at the postsynaptic membrane containing more AChR-anchoring proteins, including S-laminin and rapsyn in aged animals. In BMT-CyA EAMG, a dysregulation of the immune system in the absence of immunization is capable of inducing myasthenia. The role of these animal models in relation to pathogenesis and immunotherapy is discussed.
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PMID:Immunoregulation in experimental autoimmune myasthenia gravis--about T cells, antibodies, and endplates. 1459 88