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)

The occurrence of autoantibodies and their relation to chronic graft-versus-host disease (GVHD) have been studied in children, 100 days or more following allogenic bone marrow transplantation (BMT), mainly performed for a variety of genetic disorder. Seventeen of 40 patients had autoantibodies to thyroid microsomes, compared with none of 46 control children of similar age (p less than 0.001). The presence of these antibodies was strongly associated with chronic GVHD (14 of 20 patients), p = 0.001. IgG antibodies to the cytoplasm of squamous epithelial cells were demonstrated in 15 of 36 children following transplantation (p less than 0.001), none being found in 46 normal children. The incidence and titre of these antibodies were significantly higher in patients with chronic GVHD (p = 0.041 and p = 0.019 respectively). Despite there being a significant number of patients with antibodies to nuclei, smooth muscle and gastric parietal cells, these autoantibodies were not related to the presence of chronic GVHD. Although the mechanism of production is not known, antibodies to thyroid antigens and the cytoplasm of squamous epithelial cells may be useful markers for GVHD.
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PMID:Autoantibodies after bone marrow transplantation in children with genetic disorders: relation to chronic graft-versus-host disease. 161 16

The fetus is the preferred candidate for transplantation for a number of reasons. First, the fetal period is the earliest time at which an identified disorder can potentially be treated. If a fetus is identified with a treatable disorder in utero, and if that disorder can affect fetal development, then treatment during fetal life is potentially beneficial. A second advantage of in utero fetal HSC transplantation is the immunotolerance of the fetus, making it both a favorable donor and a favorable recipient. Finding a histocompatible donor and minimizing GVH disease are major concerns in bone marrow HSC transplantation. Fetal immuno-tolerance may eliminate the need for the former and significantly reduce the incidence and severity of the latter. The first hematologic disorders for fetal HSC transplantation may be sickle cell disease and the thalassemias, as recent technologic developments allow diagnosis in the first trimester. However, the potential targets for in utero fetal HSC transplantation are numerous and include a variety of genetic disorders of lymphocyte, platelet, leukocyte, red cell, and enzyme function. Disadvantages of in utero fetal HSC transplantation exist. First, it is necessary to have identified the fetus as being at risk for a genetic disorder, before the prenatal diagnosis can be made. This happens in one of two ways--either a previous pregnancy resulted in an affected fetus, or the parents of the fetus have been identified as being carriers of the genetic disorder.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In utero fetal hematopoietic stem cell transplantation. 286 75

Marrow transplantation is effective treatment for a number of haematological diseases in patients under the age of 50 who have an HLA-identical sibling donor. It is generally successful when used early in the treatment of aplastic anaemia. It is the only treatment that offers long-term disease-free survival for patients with acute leukaemia who have relapsed at least once, with 10-30 per cent apparent cures. Although still somewhat controversial, it appears also to be the treatment of choice for patients with acute non-lymphoblastic leukaemia in first chemotherapy induced remission and for those with chronic myelogenous leukaemia in the chronic phase since approximately 50-60 per cent of these patients are surviving after marrow transplantation in complete remission, apparently cured. Marrow grafting is the only effective treatment for many patients with inherited immunological-deficiency diseases and certain genetic storage diseases. It is being explored for the therapy of patients with lymphoma, Hodgkin's disease, multiple myeloma, small-cell lung cancer, testicular cancer, ovarian cancer and genetic disorders of haematopoiesis. Cures of congenital Fanconi anaemia, Blackfan-Diamond anaemia, osteopetrosis, and paroxysmal nocturnal haemoglobinuria have been achieved by marrow grafting. Genetic disorders associated with haemolytic anaemia and cyclic neutropenia have been cured by marrow grafting in animals. Target disorders for marrow transplantation in humans are thalassaemia major and sickle cell disease, and, indeed, a first successful transplant for treatment of thalassaemia major has recently been described (Thomas et al, 1982). Marrow transplantation has been limited by the fact that many patients do not have HLA-identical siblings and very few have monozygotic twins. The Seattle team has now explored the use of less well-matched family member donors in more than 80 patients with leukaemia. These donors share one HLA haplotype genetically with the patient and are phenotypically identical at two of the three major HLA loci on the other HLA haplotype (Clift et al, 1979). Overall, the post-transplant survival appears more a reflection of the type and stage of the leukaemia than of the marrow donor. Patients with leukaemia grafted in relapse have a projected survival of 20-30 per cent and those transplanted in remission of 50 per cent. The incidence and severity of GVHD may not be significantly different from that of patients given HLA-identical sibling marrow grafts.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Application of bone marrow transplantation in leukaemia and aplastic anaemia. 635 79

Fanconi anemia is a genetic disorder associated with diverse congenital abnormalities, progressive bone marrow failure, and increased risk of leukemia and other cancers. Affected persons often die before 30 years of age. Bone marrow transplantation is an effective treatment, but there are few data regarding factors associated with transplant outcome. We analyzed outcomes of HLA-identical sibling (N = 151) or alternative related or unrelated donor (N = 48) bone marrow transplants for Fanconi anemia performed between 1978 and 1994 and reported to the International Bone Marrow Transplant Registry. Fanconi anemia was documented by cytogenetic studies in all cases. Patient, disease, and treatment factors associated with survival were determined using Cox proportional hazards regression. Two-year probabilities (95% confidence interval) of survival were 66% (58% to 73%) after HLA-identical siblings transplants and 29% (18% to 43%) after alternative donor transplants. Younger patient age (P .0001), higher pretransplant platelet counts (P = .04), use of antithymocyte globulin (P = .005), and use of low-dose (15 to 25 mg/kg) cyclophosphamide plus limited field irradiation (P = .009) for pretransplant conditioning and cyclosporine for graft-versus-host disease prophylaxis (P = .002) were associated with increased survival. Bone marrow transplants are effective therapy for Fanconi anemia. The adverse impact of increasing age and lower pretransplant platelet count on transplant outcome favors earlier intervention, especially when there is an HLA-identical sibling donor.
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PMID:Bone marrow transplantation for Fanconi anemia. 767 Jan 20

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare genetic disorder associated with the onset early in life of overwhelming activation of T lymphocytes and macrophages invariably leading to death. Allogeneic bone marrow transplantation (BMT) from an HLA-identical related donor is the treatment of choice in patients with this disease. However, fewer than 20% of patients have a disease-free HLA-identical sibling. BMT from HLA-nonidentical related donors has previously met with poor results, with graft rejection a major obstacle in all cases. We describe BMTs from HLA-nonidentical related donors (n = 13) and from a matched unrelated donor (n = 1) performed in two centers in 14 consecutive cases of FHL. Remission of disease was achieved before BMT in 10 patients. Marrow was T-cell-depleted to minimize graft-versus-host disease (GVHD). Antiadhesion antibodies specific for the alpha chain of the leukocyte function-associated antigen-1 (LFA-1, CD11a) and the CD2 molecules were infused pre-BMT and post-BMT to help prevent graft rejection, in addition to a conditioning regimen of busulfan (BU), cyclophosphamide (CP), and etoposide (VP16) or antithymocyte globulin (ATG). Sustained engraftment was obtained in 11 of 17 transplants (3 patients had 2 transplants) and disease-free survival in 9 patients with a follow-up period of 8 to 69 months (mean, 33). Acute GVHD greater than stage I was not observed, and 1 patient had mild cutaneous chronic GVHD that resolved. Toxicity due to the BMT procedure was low. Results obtained using this protocol are promising in terms of engraftment and event-free survival within the limitations of the small sample. We conclude that an immunologic approach in terms of drugs used to obtain disease remission and a conditioning regimen that includes antiadhesion molecules in T-cell-depleted BMT from HLA genetically nonidentical donors is an alternative treatment that warrants further study in FHL patients who lack a suitable HLA genetically identical donor.
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PMID:Treatment of familial hemophagocytic lymphohistiocytosis with bone marrow transplantation from HLA genetically nonidentical donors. 938 90

Shwachman-Diamond syndrome (SDS) is a rare genetic disorder of unknown pathogenesis involving exocrine pancreatic insufficiency and hematological and skeletal abnormalities. About 25% of patients develop hematopoietic malignancies. We report on a case of acute myeloid leukemia (M2) in a 21-year-old woman affected by SDS. She was treated with conventional chemotherapy (idarubicin plus cytarabine) and reached complete remission of leukemia. After induction chemotherapy, she underwent allogeneic bone marrow transplantation (BMT). The BMT preparative regimen consisted of total body irratation (TBI) followed by cyclophosphamide. Cyclosporin A and short term methotrexate were used for graft-versus-host disease prophylaxis. After a follow-up of 12 months, she is alive leukemia free off any immunosuppressive agent. Although experience in this field is scarce, we speculate that bone marrow failure in SDS is an indication for BMT which is the only curative treatment option.
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PMID:Allogeneic bone marrow transplantation in Shwachman-Diamond syndrome with malignant myeloid transformation. A case report. 1229 32

The use of mesenchymal stem cells (MSC) for tissue and organ regeneration offers advantages because the MSC contain multipotent progenitor cells and reported to be immunoprivileged as well as immunosuppressive. Therefore, cell therapy with allogeneic MSC has been reported as a promising treatment for severe acute graft versus host disease (GVHD). We reported a pilot study for GVHD treatments using a small number of allogeneic MSC. We also reported that MSC can show osteogenic differentiation capability when implanted in vivo as well as cultured in vitro. Based on these findings, we attempted to use allogeneic MSC for the treatment of genetic disorder of hypophosphatasia patient. Present paper summarizes our clinical experiences of allogeneic MSC for the purpose of regenerative medicine.
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PMID:[Regenerative therapy using allogeneic mesenchymal stem cells]. 2224 8

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder which most commonly manifests as pulmonary emphysema. Accordingly, alpha-1 antitrypsin (AAT) augmentation therapy aims to reduce the progression of emphysema, as achieved by life-long weekly slow-drip infusions of plasma-derived affinity-purified human AAT. However, not all AATD patients will receive this therapy, due to either lack of medical coverage or low patient compliance. To circumvent these limitations, attempts are being made to develop lung-directed therapies, including inhaled AAT and locally-delivered AAT gene therapy. Lung transplantation is also an ultimate therapy option. Although less common, AATD patients also present with disease manifestations that extend beyond the lung, including vasculitis, diabetes and panniculitis, and appear to experience longer and more frequent hospitalization times and more frequent pneumonia bouts. In the past decade, new mechanism-based clinical indications for AAT therapy have surfaced, depicting a safe, anti-inflammatory, immunomodulatory and tissue-protective agent. Introduced to non-AATD individuals, AAT appears to provide relief from steroid-refractory graft-versus-host disease, from bacterial infections in cystic fibrosis and from autoimmune diabetes; preclinical studies show benefit also in multiple sclerosis, ulcerative colitis, rheumatoid arthritis, acute myocardial infarction and stroke, as well as ischemia-reperfusion injury and aberrant wound healing processes. While the current augmentation therapy is targeted towards treatment of emphysema, it is suggested that AATD patients may benefit from AAT augmentation therapy geared towards extrapulmonary pathologies as well. Thus, development of mechanism-based, context-specific AAT augmentation therapy protocols is encouraged. In the current review, we will discuss extrapulmonary manifestations of AATD and the potential of AAT augmentation therapy for these conditions.
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PMID:Alpha-1 Antitrypsin Substitution for Extrapulmonary Conditions in Alpha-1 Antitrypsin Deficient Patients. 3072 84