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)

Data were obtained from 46 patients with severe aplastic anemia (SAA) who received bone marrow transplants (BMT) from donors other than genotypically HLA-identical siblings. The data were collected in the SAA Registry of the European Bone Marrow Transplant Group. The donors were non-HLA-identical siblings in six cases, parents in 28 cases, a son in one case and unrelated individuals in 11 cases. Fifteen donor-recipient pairs were HLA-A, -B and -DR identical and mutually non-reactive in mixed lymphocyte culture; nine were mismatched at one locus, 17 were mismatched at two or more loci and in five cases data were not available for D/DR determinants. Actuarial survival was predicted by the degree of mismatch. It was 45% for phenotypically HLA-identical grafts, 25% for grafts mismatched at one locus and 11% for graft mismatched at more than one locus. Whether the graft was derived from a family member or an unrelated donor seemed to be less important and results were comparable. Age, patient sex and year of transplant had no significant influence on survival. The use of cyclosporine (CSA) for graft-versus-host disease (GVHD) prophylaxis (n = 21, survival 34%) appeared superior to both methotrexate (n = 9, survival 11%) and to CSA with T cell depletion of donor marrow (n = 13, survival 14%). The causes of death were rejection (n = 15), GVHD (n = 13), pneumonitis (n = 5) and infection (n = 1). Twelve patients are alive at 16-84 months post-BMT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone marrow transplantation for severe aplastic anemia from donors other than HLA identical siblings: a report of the BMT Working Party. 306 21

An infant with severe immune deficiency received bone marrow from an HLA-A, -B, -DR matched, mixed leucocyte reaction non-reactive first cousin. The donor marrow was fractionated on a discontinuous Percoll gradient and before infusion was treated with the anti-human T lymphocyte antibody, HuLy-m1, and rabbit serum as a source of complement. Methotrexate was given during the following two weeks. A rise in the peripheral blood lymphocyte count, indicating engraftment, occurred six weeks after transplantation. There was no clinical evidence of graft versus host disease (GVHD). Engraftment has been sustained for one year and the patient is in normal health and has normal in vitro immunological function. In vitro treatment of human marrow with HuLy-m1 allows stable engraftment and may be useful in attempting to diminish or prevent GVHD.
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PMID:Immunological reconstitution in a patient with severe combined immune deficiency using non-sibling bone marrow depleted of T cells with HuLy-m1. 353 67

Allogeneic bone marrow transplantation (BMT) successfully corrected type I thrombasthenia in a 4-year-old boy. The donor was his HLA-A, B and D identical 14-year-old brother who was heterozygous for thrombasthenia. A first transplant after conditioning with cyclophosphamide and thoracoabdominal irradiation was rejected, but a second transplant using CCNU, cyclophosphamide, procarbazine and horse antihuman thymocyte globulin in the preparative regimen was successful. Engraftment was proven by studies of platelet membrane antigens, PLA1 and glycoprotein IIb/IIIa complex and by platelet function studies. Haemorrhagic manifestations completely disappeared; platelet membrane markers and clot retraction returned promptly to normal values, and platelet aggregation tests more slowly. Twenty-four months after bone-marrow transplant, the patient was well with mild chronic hepatic graft versus host disease. BMT therefore appears to be a possible treatment for severe inherited platelet disorders.
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PMID:Complete correction of Glanzmann's thrombasthenia by allogeneic bone-marrow transplantation. 388 99

A new procedure for enrichment of marrow precursors and removal of T lymphocytes from large volumes of human bone marrow, involving initial differential agglutination of T lymphocytes and mature marrow elements with soybean agglutinin, followed by rosetting with sheep red blood cells, was used to fractionate marrow cells from an HLA-A, B, DR non-identical, MLC non-reactive, paternal donor for transplantation into an infant with acute leukaemia. This transplant became completely engrafted and resulted in full recovery of normal, donor-derived haematopoietic function without graft-versus-host disease, sustained for 11 weeks after transplantation, at which time the patient's leukaemia recurred. Subsequently, the patient received chemotherapy and achieved a remission with regeneration of normal marrow cells of donor origin. The patient's course demonstrated the potential of lectin-separated marrow grafts to restore durable haematopoiesis, without graft versus host disease, in a lethally irradiated allogeneic host.
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PMID:Transplantation for acute leukaemia with HLA-A and B nonidentical parental marrow cells fractionated with soybean agglutinin and sheep red blood cells. 611 10

130 patients with severe aplastic anaemia, conditioned with high-dose cyclophosphamide, showed sustained engraftment of marrow from HLA-identical siblings. Most patients (55%) had no acute graft-versus-host disease (GVHD), 11% had transient grade I, and 34% had moderate to severe (grades II-IV) acute GVHD. The relation between the donors' (and the patients') HLA antigens and the incidence of grades I-IV acute GVHD was explored. There was no association with HLA-A antigens, but a significant correlation with HLA-B antigens. Patients with HLA-B18 had an estimated acute GVHD incidence nearly three times that of other patients, whereas the incidence in the presence of HLA-B8 or HLA-Bw35 was estimated to be about half that in the absence of these alleles.
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PMID:Association between HLA-B antigens and acute graft-versus-host disease. 613 49

1. According to a recent hypothesis, based on similarities between chronic graft versus host disease and primary biliary cirrhosis (PBC), immune reactions against histocompatibility (HLA) antigens may be responsible for the bile duct damage and extrahepatic lesions of PBC. 2. Previous studies have demonstrated autoimmune reactions in PBC against normal human biliary tract antigens. To equate these findings with the above hypothesis, it has been suggested that the biliary antigens are related to the HLA system and, in the present study, this possibility has been investigated by: (a) using preparations of the biliary antigens to inhibit the lymphocytotoxic activity of standard HLA-typing sera against normal lymphocytes, and (b) employing guinea-pig antisera raised against the biliary antigens as 'typing reagents' in the lymphocytotoxicity test to determine whether these antisera recognize HLA components on the surfaces of normal lymphocytes. 3. No inhibition by the biliary antigens of the reaction of two standard typing sera against T-and B-lymphocytes from two normal healthy donors (covering nine HLA-A, -B, -C and three HLA-DR loci antigens) was observed. Conversely, the guinea-pig antisera showed no reaction against these lymphocytes. 4. The results suggest that the biliary tract antigens are probably not related to 'common' antigenic determinants associated with the HLA system.
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PMID:Relationship between primary biliary cirrhosis and chronic graft versus host disease: investigation of histocompatibility (HLA) antigenic determinants in biliary tract antigens. 618 65

In this chapter, we have considered the theoretical and practical background of bone marrow transplantation. The immune response and its regulation by genes within the major histocompatibility complex, particularly of the I region of the mouse and of the HLA-D/DR region in man, is of central importance in both graft acceptance (rejection) and graft-versus-host disease. Methods which are available for typing alleles at the HLA-A, -C, -B, -DR and complotype (BF, C2, C4A, C4B) loci, have been considered in detail. The extent to which recombination affects specific alleles on haplotypes within families is discussed, as is the occurrence of linkage disequilibrium and extended haplotypes in populations of unrelated individuals. Because the HLA-DR and complotype region in man is thought to be critical for the success of bone marrow transplantation, methods for typing of HLA-D by both the HTC and PLT approaches have been examined. Although HLA-D/DR assignments are easily made in normal subjects, they are ambiguous in about 50 per cent of candidates for bone marrow transplantation, including, particularly, patients with aplastic anaemia, leukaemia, and severe combined immunodeficiency. In this setting, it is particularly important to obtain additional information by modification of HLA-D typing procedures and through complotype and GLO allele determinations in all family members. Finally, we can hope that there will be an increased possibility of using non-family donors through methods for removing cytotoxic T cells from donor marrow and through the identification, in the general population, of individuals who are genotypically similar or identical to the recipient. In this regard, the recognition that some 30 per cent of chromosome 6 in caucasians (50 per cent of individuals) bear extended haplotypes, which include a relatively fixed set of alleles particularly in the HLA-B, -DR, complotype and GLO regions, offers considerable promise.
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PMID:The MHC in human bone marrow allotransplantation. 622 38

Major histocompatibility complex-determined antigens were originally identified as a consequence of their ability to induce rejection of tissue grafts between organisms that are not genetically identical. Currently, much is known about their biochemical nature and intended biological functions. Major histocompatibility complex antigens are found on three types of glycoprotein molecules. One type (class I) is associated with beta 2-microglobulin in the cell-surface membranes of all body tissues and includes H-2K and D molecules in mice and HLA-A, B, and C molecules in humans. These antigens are the major cause of rejection of transplanted organs. The other two types of glycoproteins (class II) are noncovalently linked to each other, are found in the cell-surface membranes of a limited number of cell types, and include H-2-Ia molecules in mice and HLA-DR molecules in humans. They are noted for their ability to elicit graft-versus-host disease. Both class I and class II molecules are, however, important for the immune recognition of pathogens, although the types of responses they modulate are different. Class I molecules are important in the recognition of cell-surface antigens, whereas class II molecules control responsiveness to soluble antigens. Major histcompatibility complex-encoded molecules are also involved in certain autoimmune diseases. As our understanding of major histocompatibility complex-controlled immune responsiveness broadens and hybridoma and gene-cloning technology advances, specific enhancement of desired immune responses and suppression of deleterious ones will most likely become possible.
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PMID:Immune-response gene-associated antigens (Ia/DR). Structure and function in immunologically related diseases. 640 18

A newborn with graft-vs-host (GVH) disease following an exchange transfusion was treated by attempting to eradicate the incompatible graft and to reconstitute the child hematologically and immunologically with a bone marrow transplant. The patient was a female term infant (blood group B, Rh+ Coombs test positive) who received a one-unit group O, Rh- exchange transfusion from an unrelated female donor for hyperbilirubinemia due to ABO incompatibility on day 2. Signs of acute GVH disease began on day 8 and the clinical diagnosis was supported by skin biopsy. With antithymocyte globulin and high dose dexamethasone, the GVH reaction improved somewhat. Cyclophosphamide, 200 mg/kg total dose, was given over four days followed by a marrow graft from a brother who was HLA-A, B identical, and probably also D locus compatible in mixed lymphocyte culture. All signs of GVH resolved with cyclophosphamide treatment and hematologic reconstitution was evident by 14 days after transplant. Two weeks later the GVH reaction and aplastic anemia recurred and Y chromatin was detected in only 6% of marrow cells. The infant died on day 80. Autopsy showed disseminated candidiasis, disseminated cytomegalovirus infection, thymic dysplasia, hypoplastic marrow, and other histopathologic changes consistent with GVH disease. The persistence of female cells in blood and bone marrow and the destruction of the reconstituted marrow suggest that the original incompatible transfusion-derived graft was not eliminated and that it ultimately rejected the histocompatible marrow graft.
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PMID:Probable graft-vs-graft reaction in an infant after exchange transfusion and marrow transplantation. 680 70

As of 31 December 1979, 39 patients in Seattle have received marrow grafts from donors other than HLA genotypically identical siblings. Sixteen transplants were between siblings, 21 from a parent to a child, one from a paternal uncle, and one from an unrelated donor. Ten patients had aplastic anemia and 29 had a hematological malignancy. As of 1 February 1980, only one of the ten patients transplanted for aplastic anemia is currently alive (greater than 1048 days) with a normal marrow and without graft-versus-host disease. This surviving patient was untransfused and received marrow from an HLA phenotypically identical mother. There were five episodes of graft rejection among the ten aplastic patients. Among the 29 patients transplanted for hematological malignancy, 12 (42%) are surviving from greater than 64 to greater than 995 days. Twelve of 29 patients were transplanted while in remission and eight (75%) are alive from greater than 148 to greater than 790 days. The two most frequent causes of death were relapse of leukemia and interstitial pneumonia. Only two patients died from complications clearly related to graft-versus-host disease. Five of the surviving patients were phenotypically identical with their donor for HLA, while seven were incompatible for some HLA determinants. One patient--donor pair was incompatible for HLA-D and DR as a result of HLA-B/D recombination, and six pairs were incompatible for HLA-A and/or B.
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PMID:Marrow transplantation from donors other than HLA identical siblings. 702 18


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