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)

Bone marrow transplantation can be considered in any disease state resulting in the malfunction or absence of part or all bone marrow elements. Diseases such as aplastic anemia, leukemia, and immunodeficiency disease are being treated with bone marrow transplantation. As with any organ transplant, graft rejection is a possibility. In bone marrow transplantation, there is the additional, unique problem of graft versus host disease. In order to prevent or minimize graft rejection, the immunocompetence of the recipient and the degree of disparity between donor and recipient at the major histocompatibility complex (MHC) loci are considered. The results of bone marrow transplantation are variable, and the mortality rate is still relatively high. However, progress is being made, and in many instances, normal bone marrow function can be restored in patients with whom other treatment has failed.
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PMID:Bone marrow transplantation. 3 23

Leucocyte group 5 has two dominant alleles (5a and 5b) which segregate independently of the major histocompatibility complex. The group-5 system was studied in a Caucasian population of controls and patients with acute lymphoblastic leukaemia. The 5a gene frequency was 0-09 in 72 controls and 0-38 in 39 patients with acute lymphoblastic leukaemia (p less than 0-001). 15 patients with acute myelogenous leukaemia and 12 patients with aplastic anaemia had 5a and 5b frequencies similar to those seen in the control population. It is concluded that 5a or a closely linked gene is involved in susceptibility to acute lymphoblastic leukaemia.
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PMID:Association between leucocyte group-5a antigen and acute lymphoblastic leukaemia. 6 10

An IgM antibody, present in the serum of a female patient with aplastic anemia, is described that reacted in a modified complement-dependent cytotoxicity test with a subset of the B cells from HLA-A2-positive, but not HLA-A2-negative males. With the exception of two HLA-A2 positive females, the antibody did not react with other cells from either HLA-A2-positive or HLA-2-negative females. The cells of one of these and from HLA-A2-positive males were able to absorb the antibody from the serum. Cells from other donors were unable to absorb the antibodies. The mononuclear cells of the same patient were cytolytic in cell-mediated lympholysis (CML) for phytohemagglutinin blasts from all HLA-A2-positive males and one of the females reacting with antibody, but not with blasts from HLA-A2-negative males and all other females. Thus, the results obtained with the antibody in the complement-dependent cytotoxicity test showed an almost perfect correlation with cytolysis in CML tests. These results suggest that the IgM antibody may be the first example with major histocompatibility complex restriction. Because the antibody reacted with the cells from two female donors, the restricting determinant is not, in all probability, the H-Y determinant.
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PMID:Major histocompatibility complex-restricted antibody reactivity mainly, but not exclusively, directed against cells from male donors. 50 Dec 84

This report summarizes the experience with 25 patients who received a second marrow transplant. The marrow donor for the first transplant was an identical twin in four cases and a sibling matched at the major histocompatibility complex in 21 instances. The donor for the second transplant was the same as the first except for three patients whose second donor was another matched sibling. Nine patients with aplastic anemia rejected their first graft. Four of these patients were prepared for the second graft with a regimen of procarbazine and antithymocyte globulin (ATG) followed by cyclophosphamide or total body irradiation and were successfully regrafted. One rejected the second graft, two died of septicemia and one is alive and well 10 months after the second graft. Twelve patients with hematologic malignancy had a recurrence of disease after the first transplant. Despite preparation for the second graft with a variety of intensive chemotherapeutic regimens, the five patients who did not succumb to infection showed an early recurrence of disease. Four patients with hematologic malignancy had a failure of the first graft for unknown reasons, possibly related to the administration of ATG or methotrexate. One patient prepared for the second graft with procarbazine and ATG showed evidence of engraftment but died of infection. Two out of three patients given no additional preparation were successfully grafted. One died of recurrent central nervous system leukemia after 18 months and one is alive and well 26 months after the second graft.
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PMID:Experience with second marrow transplants. 78 96

The graft-versus-host reaction (GVHR) in both mice and humans can lead to the development of a broad spectrum of clinical and pathological symptoms. These symptoms are strikingly similar to those of a number of diseases of proven or presumed immunological origin, such as systemic lupus erythematosus (SLE), other collagen vascular diseases, lymphoproliferative disease, and aplastic anemia. The purpose of our investigation was to describe the immunological and pathological events that take place in the course of graft-versus-host disease (GVHD) and to gain insight into the cellular mechanisms underlying these events. To this end, a model was employed in which nonirradiated F1 mice were used as recipients of parental lymphoid cells. By pathological manifestations, 2 basic forms of GVHD can be distinguished in such non-irradiated F1 recipients: One is acute GVHD which is often lethal. It is characterized by a variety of suppressive (hypoplastic) pathological symptoms, including a severe hypoplasia of the lymphohemopoietic system accompanied by aplastic anemia and hypogammaglobulinemia. The other basic form is characterized by stimulatory symptoms, such as persistent lymphoid hyperplasia, formation of autoantibodies, and development of pathological symptoms reminiscent of SLE and other collagen vascular diseases. The suppressive pathological graft-versus-host (GVH) symptoms are caused by T suppressor/killer (TS/K) cells of the donor which react towards allogeneic class-I-structures of the F1 recipient's major histocompatibility complex (MHC). The stimulatory pathological GVH symptoms, by contrast, are caused by donor T helper (TH) cells which react toward the recipient's allogeneic class-II-MHC structures. The possible implications of these observations for the pathogenesis of a number of GVH-like diseases in humans are discussed. The hypothesis is advanced that some of these GVH-like conditions, which arise either e causa ignota or after exposure to certain viruses or drugs, are caused by T lymphocytes reacting against self-MHC structures on lymphohemopoietic cells that were rendered "foreign". By analogy to GVHD, it is conceivable that the development of either stimulatory or suppressive GVH-like symptoms in individuals exposed to a given virus or sensitizing drug depends not on the etiologic agent per se, but on whether the predominant response is made by the individual's TH or TS@K cells. This, in turn, might depend on whether the agent becomes immunogenic in combination with class-II or class-I alloantigens.
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PMID:Pathogenesis of graft-versus-host reactions (GVHR) and GVH-like diseases. 315 4

We have investigated T cell abnormalities present in blood of two patients with aplastic anaemia and hypogammaglobulinaemia. There was a marked increase in class II, major histocompatibility complex, HLA-DR+ antigen, and interleukin-2 receptor (Tac+) bearing CD4+ helper/inducer T cells, and a concurrent reduction of CD8+ suppressor/cytotoxic T cells. These CD4+ T cells produced an elevated proliferative response to phytohaemagglutinin and concanavalin A. Interestingly, the T cell subset mainly responsible for elevated production of the lymphokine, interleukin-2, under the stimulus of phytohaemagglutinin, was characterized as belonging to a CD4+ T cell subset. Functional studies, using a pokeweed mitogen driven IgG, IgA and IgM synthesis, demonstrated a correlation between CD4+ T cell deficient helper function for B cell differentiation and the clinical finding of the patient's hypogammaglobulinaemia.
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PMID:Phenotypic and functional T cell subset abnormalities in patients with aplastic anaemia and hypogammaglobulinaemia. 326 16

The transfusion of foreign blood products (expressing non-self histocompatibility antigens) leads to an immune response in the transfusion recipient. This may result in a memory response to subsequent transfusions, and in patients undergoing marrow transplantation for the treatment of aplastic anemia in an increased risk of marrow graft rejection. We have used the canine model of marrow transplantation as an in vivo indicator system for the occurrence of post transfusion sensitization. Our results show that sensitization can occur in response not only to major histocompatibility complex (DLA) antigens but also to minor (non-DLA) antigens. Our studies suggest that the antigens involved are probably expressed on leukocytes but not on RBC and platelets. Among leukocytes the sensitizing population appears to be contained within mononuclear cells, presumably large Ia positive cells which show accessory cell function in vitro. The responsible antigens are apparently not expressed on T lymphocytes. Our findings are in agreement with the hypothesis that dendritic cells play a central role in transfusion-induced sensitization. Their sensitizing ability can be abrogated by exposure to UV light prior to transfusion. It is conceivable that exposure to UV light alters the function of Ia antigens which in turn results in defective antigen presentation and consequently a lack of sensitization of the recipient. Alternatively non-DLA antigens on donor cells could be modified by exposure to UV light thus escaping recognition by the recipient. The exact mechanism remains to be determined.
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PMID:Modification of immunogenicity of transfusion products. 351 57

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

Bone marrow transplantation is an accepted therapy for hematologic malignancies, aplastic anemia, metabolic disorders, and solid tumors. However, graft-versus-host disease (GVHD) and failure of engraftment have limited the widespread application of this technology to nonmalignant disease states. The use of purified bone marrow stem cells has been suggested as an approach to promote engraftment yet avoid GVHD. Although bone marrow stem cells, purified by cell sorting, engraft and repopulate lethally irradiated genetically identical recipients, they do not engraft in major histocompatibility complex (MHC)-disparate allogeneic recipients. We report for the first time the characterization of a novel cell population of donor bone marrow origin, separate from the hematopoietic stem cell, that facilitates engraftment of purified allogeneic bone marrow stem cells in an MHC-specific fashion without causing GVHD. Although 1,000 purified stem cells (c-kit+/Sca-1+/lineage-) reliably repopulate syngeneic mouse recipients, 10 times that number do not engraft in MHC-disparate allogeneic recipients. The addition of as few as 30,000 facilitating cells (CD8+/CD45R+/TCR-) is sufficient to permit engraftment of purified stem cells in MHC-disparate recipients. The cell surface phenotype of this purified cellular population differs significantly from other characterized lineages of lymphoid or myeloid origin. Based on multiparameter rare-events cell sorting, the facilitating fraction is CD8+, CD3+, CD45R+, Thy 1+, class IIdim/intermediate but alpha beta-TCR- and gamma delta-TCR-. This cellular population comprises approximately 0.4% of the total bone marrow and is separate from the hematopoietic stem cell. The coadministration of purified facilitating cells plus stem cells to optimize engraftment yet avoid GVHD may expand the potential application of bone marrow transplantation to disease states in which the morbidity and mortality associated with conventional BMT cannot be justified.
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PMID:Phenotypic characterization of a novel bone marrow-derived cell that facilitates engraftment of allogeneic bone marrow stem cells. 791 63

The most effective treatment currently available for children with severe aplastic anemia is bone marrow transplantation using a sibling donor who is completely matched with the patient at the major histocompatibility complex. Only a minority of patients, however, will have such a donor and other treatments which have been used include the use of single agent immunosuppression, multi-agent immunosuppression, multi-agent immunosuppression with hemopoietic growth factors, and the use of allogeneic stem cell transplantation using mismatched family members, unrelated individuals or placental blood. Of these approaches the most promising appears to be the use of combination immunosuppressive therapy plus hemopoietic growth factors. This paper reviews the current results obtained in using these various methods of treating children with severe aplastic anemia who lack a matched sibling donor.
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PMID:What is the most effective treatment of children with severe aplastic anemia who lack a matched sibling donor? 897 7


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