Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient with severe combined immunodeficiency received seven transplants of bone marrow from an HLA-B-compatible and HLA-D-compatible unrelated donor in an attempt to provide immunologic reconstitution. The first four transplants achieved restricted engraftment with evidence of rudimentary immunologic function. A fifth transplant, given after low-dose cyclophosphamide, produced reconstituion of cell-mediated immunity. Marrow aplasia developed after recontamination with a nonpathogenic microflora. Transplantation of marrow previously stored in liquid nitrogen was ineffective. A subsequent transplant, administered after high-dose cyclophosphamide, achieved durable engraftment, with complete hematopoietic and immunologic reconstitution. Seventeen months after transplantation, full functional engraftment persists. Graft-versus-host disease has been chronic and moderately severe, but limited to the skin and oral mucosa. Transplantation of marrow from unrelated histocompatible donors may provide a useful treatment for patients with severe combined immunodeficiency or aplastic anemia who lack a matched sibling or related donor.
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PMID:Reconstitution in severe combined immunodeficiency by transplantation of marrow from an unrelated donor. 2 51

A patient with aplastic anemia who was found to be homozygous for an HLA-D determinant shared by her unrelated parents achieved sustained engraftment and full restoration of hematopoietic and lymphoid function following a transplant from an HLA-A and -B nonidentical, ABO incompatible sibling who was heterozygous for the shared HLA-D specificity. Transplantation was complicated by transient graft-versus-host disease of moderate severity, which resolved completely following treatment with antithymocyte globulin and prednisone. The case indicates that patients found to be HLA-D-homozygous may be successfully transplanted from HLA-D-heterozygous sibling donors despite HLA-A and HLA-B incompatibilities, and thus further demonstrates the importance of the HLA-D region as a marker of donor-host histocompatibility.
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PMID:Successful transplantation of marrow from an HLA-A, -B, -D mismatched heterozygous sibling donor into an HLA-D-homozygous patient with aplastic anemia. 3 52

With the aim to detect genotypically identical donors for patients suffering from some type of leukemia or aplastic anemia, HLA antigens and MLC reactivity were determined in 72 families, having together 209 children. HLA identical, MLC negative sibling donors were found for 31 patients, i.e. 43%. Compared to the healthy population, no significant differences were found in the frequency of HLA antigens and haplotypes in 58 leukemic patients. Two recombinations were recorded, one between the loci HLA-A and HLA-B, and the other one between HLA-B and HLA-D/DR. Only 9 persons (2.5%) homozygous for HLA-D antigens were found in the whole series of 353 subjects investigated.
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PMID:[Possibilities of finding identical HLA donor-recipient pairs for bone marrow transplantation]. 214 57

HLA antigens and MLC reactivity were ascertained in 69 families, having altogether 198 children, with the aim to find genotypically identical donors for patients suffering from some type of leukemia or aplastic anemia. HLA identical, MLC negative sibling donors were found for 29 patients, i.e. 42.03%. In 55 leukemic patients the frequency of HLA antigens and haplotypes was calculated. No significant differences were found as compared to the healthy population. One recombination between HLA-A and HLA-B and one between HLA-B and HLA-D/DR loci were observed.
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PMID:Occurrence rate of the HLA-identical pair donor-recipient for bone marrow transplantation. 214 19

A three-year-old boy with severe aplastic anemia (HLA-A1,B8(Bw6), Cw7,DR3, MB2, MT2, SB4/A1,B8 (Bw6), Cw7,DR3,MB2,MT2,SB-) received a bone marrow transplant from a phenotypically HLA-identical, SB-compatible female unrelated donor. This donor was selected from eighteen HLA-A1,-B8,-blood donors after extended serotyping, mixed leukocyte culture testing and secondary proliferation assays with primed lymphocyte typing reagents specific for SB. Although patient cells proliferated well as responders in MLR, their stimulatory capability was greatly impaired. Because the patient had inherited the same serological HLA-D haplotype from each parent, it was concluded that a compatible unrelated donor must be homozygous for the same HLA-D antigens as the patient. This HLA-D homozygosity was demonstrated by the lack of MLR responses of both parents to stimulators from the donor. The SB typing results suggested SB compatibility because both the patient and the donor typed as SB4,-. Following bone marrow transplantation, there was rapid hematopoietic engraftment. The patient developed severe diarrhea caused by graft-versus-host disease of the gastrointestinal tract, which necessitated hyperalimentation. He is currently eighteen months posttransplant with full hematopoietic reconstitution and moderate chronic skin graft-versus-host disease.
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PMID:Bone marrow transplantation for severe aplastic anemia using a phenotypically HLA-identical, SB-compatible unrelated donor. 622 16

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

Skin biopsies of 26 patients with leukemia and seven patients with aplastic anemia were investigated before and at different stages after allogeneic bone marrow transplantation (BMT) to establish the immunological criteria which distinguish skin alterations during normal reconstitution from dermal lesions mediated by graft-versus-host disease (GvHD). Of the 33 patients studied 27 presented with clinically diagnosed acute and/or chronic GvHD, one patient died of bone marrow rejection. Immunohistological analysis of the respective skin biopsies with selected monoclonal antibodies against human leukocyte antigens (HLA) and differentiation antigens of the lympho-hematopoietic cells revealed low dermal mononuclear cell counts with phenotypically normal constituents in five cases with uncomplicated reconstitution post-grafting. In contrast, increased dermal cellular infiltrates predominantly consisting of Lyt 3+, OKT 8+ T-lymphocytes, as well as of a large number of Ia-like (immune response associated = HLA-D) determinant + monocytes/macrophages were observed in all patients with active acute/chronic GvH reactivity. As sign of activation simultaneous expression of HLA-D region products was also found on a subset of the invading OKT8+ T-lymphocytes. Progression of GvHD was associated with additional surface staining of keratinocytes for Ia-like determinants. Loss of Ia-like determinant+, OKT6+ dentritic epithelial cells in all leukemic patients, as well as in patients with aplastic anemia with or without GvHD suggested damage of Langerhans cells due to the previous radiotherapy and/or specific immunological destruction. In patients with fatal outcome of GvHD prolonged reduction of these dentritic epithelial cells seemed to be indicative of impaired immune reconstitution or bone marrow dysfunction. Thus immunopathological features of skin GvHR may enable early recognition and prognostic evaluation of this disease possibly allowing more effective therapy.
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PMID:Immunohistological skin alterations in allogeneic bone marrow transplantation. 638 72

A patient with constitutional Fanconi-like aplastic anemia who developed a preleukemic state was transplanted with bone marrow from his HLA-identical MLC-negative brother. Before transplantation his mononuclear leukocytes were found to have a defective stimulating and responder capacity in mixed leukocyte culture with cells of an unrelated individual. After removal of T cells the stimulating capacity was completely restored. MLC testing with separated cell fractions seems important to establish HLA-D identity with a possible donor, especially when MLC tests with unseparated cells are negative.
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PMID:Defective stimulating capacity of leukocytes in mixed leukocyte culture in constitutional aplastic anemia caused by suppressor T cells. A case study. 644 53

Bone-marrow transplantation for severe aplastic anaemia was performed in a 14-year-old boy in 1969. The transplanted marrow was not HLA identical: there was HLA-D incompatibility between the female donor and the recipient. The patient had had several blood transfusions and one course of cytostatic conditioning before the transplantation. Six years later he had carcinoma of the colon which was completely removed at surgery. Ten years after transplantation, chimaerism was demonstrated in the recipient who was then haematologically and clinically healthy and in full employment. The bone-marrow transplantation can thus be considered as successful.
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PMID:[Successful bone-marrow transplantation after eleven years (author's transl)]. 699 88

Clinical histocompatibility testing has now developed to a stage where it is possible to select related bone marrow donors for some patients, when HLA genotypically identical siblings are not available. The most common type of such donors are the HLA phenotypically or HLA-D phenotypically identical related donors. The HLA-D homozygous recipient offers special options, since these patients can potentially receive bone marrow transplants from any of the parents or from HLA-haploidentical siblings. The studies in SCID have demonstrated that HLA-D compatibility in spite of HLA-A or B incompatibilities can be tolerated and there is now accumulating evidence that even patients with aplastic anemia or acute leukemia can be successfully treated with such bone marrow grafts.
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PMID:Histocompatibility testing for clinical bone marrow transplantation and prospects for identification of donors other than HLA genotypically identical siblings. 702 35


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