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)

A 16 year old boy underwent allogeneic bone marrow transplantation (BMT) from an human leukocyte antigen (HLA)-identical sibling for severe aplastic anaemia. He was symptomatic for 7 years before transplantation and had received multiple red blood cell and platelet transfusions. Conditioning for BMT consisted of cyclophosphamide, antilymphocyte globulin and total lymphoid irradiation. Engraftment was rapid, there was no evidence of rejection despite the history of multiple blood product transfusions and he did not develop acute or chronic graft versus host disease. He was well for the first 8 months after transplantation but then developed fevers, interstitial pneumonia, herpes simplex infections and cytomegalovirus enteritis. Serological studies revealed antibodies to human immunodeficiency virus (HIV) and he was considered to have acquired immune deficiency syndrome (AIDS). Retrospective analysis of the serum samples showed that he was seronegative for HIV until approximately 10 months before transplantation when his serum became HIV positive. Lymphocyte function studies done after transplantation suggested immunologic recovery at 3 months post-transplant with a brisk though subnormal response to phytohaemagglutinin stimulation. T cell subset analysis performed subsequently showed complete absence of CD4 positive cells indicating immune incompetence which was associated with clinical features of AIDS. Bone marrow transplantation had failed to produce sustained immunologic reconstitution and prevent the progression of HIV to which he ultimately succumbed.
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PMID:Failure of allogeneic bone marrow transplantation to benefit HIV infection. 149 64

A 26-year-old male with chronic myelogenous leukemia in lymphoid blast crisis received a bone marrow transplant (BMT) from a phenotypically identical, mixed lymphocyte reaction (MLR)-weakly positive unrelated male volunteer donor. The volunteer was obtained from the Tokai Marrow Donor Bank (TMDB), which was established in Japan in 1989. This donor was selected from volunteer donors who were identical with our patient at the HLA-A,B loci, followed by matching at HLA-DQ, DR loci. On MLR testing, the donor's cells showed no response, but the patient's cells showed a low response to the donor's cells (relative response index 0.29). The patient showed rapid hemopoietic engraftment. He developed acute graft-versus-host disease (GVHD) with vesicle formation on palms and soles and mild liver damage, which were successfully treated with intravenous prednisolone 1 mg/kg per day. Although he also suffered from interstitial pneumonitis on day 64 and localized varicella-zoster infection on day 87, and has suffered from moderate stomatitis and dry skin characteristic of chronic GVHD, he is currently 22 months post-transplant with hematological remission and has a normal daily social life.
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PMID:Bone marrow transplantation for chronic myelogenous leukemia in blastic phase using a phenotypically identical unrelated volunteer donor. Nagoya Bone Marrow Transplantation Group (NBMTG), Tokai Marrow Donor Bank (TMDB). 149 15

The transplantation of multiple abdominal viscera including liver-duodenum-pancreas, liver-stomach-duodenum-pancreas, and liver-intestine is being performed with increasing frequency and success. These procedures and other variations are derived from a seldom used multiple visceral operation in which all of the foregoing organs are transplanted in bloc. It is described here how the full multiple visceral transplantation and its less extensive derivatives are based on the same principles of procurement, preservation, and postoperative management. With all of these multiple organ permutations and with intestinal transplantation alone, management is complicated by inclusion in the grafts of a large lymphoreticular component which is capable of causing graft versus host disease (GVHD). Because of a systematic error in therapeutic philosophy, past efforts have been directed at altering or damaging the lymphoreticular cells by pretreatment or of the donor of the organs with drugs, irradiation or other means. From recent observations, the alternative approach is suggested of keeping these lymphoid depots intact which then become the site of 2 way cell traffic after transplantation. Under powerful immunosuppression such as that provided with FK 506, the donor lymphoreticular cells can circulate in the recipient without causing clinical GVHD, and the lymphoreticular cells in the graft become those of the recipient (local chimerism) without causing rejection. Even with avoidance of rejection and GVHD, metabolic interrelations between the grafted organs, and also between the graft organs and retained recipient viscera can affect the fate of the individual transplanted organs or retained recipient organs. The best delineated of these metabolic influences are mediated by the endogenous splanchnic hepatotrophic factors of which insulin has been the most completely studied.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Transplantation en masse of abdominal organs]. 155 35

The authors report an 18-year-old female who developed severe hemolytic reaction and delayed neutrophil recovery after bone marrow transplantation (BMT) for aplastic anemia from her HLA-identical sibling. She had received much transfusion (61 units of red blood cells including 4 units of fresh whole blood from her parents and 350 units of platelets) for 12 years before BMT. To prevent graft rejection, she received an intensified preparative regimen consisted of cyclophosphamide 200 mg/kg followed by 5 Gy total body irradiation and 5 Gy total lymphoid irradiation. Prophylaxis for GVHD was short term methotrexate and cyclosporin-A. Despite of the removal of the red cells from the marrow, marked hemolytic reaction caused by antibodies directed to rh" (E) and hr' (c) red cell antigens was observed when rh" (E) and hr' (c) positive donor erythroid began to recover. The recovery of neutrophils, especially the fraction of segmented cells was also delayed. Flow cytometry showed that the serially collected patient's sera reacted to neutrophils derived from both patient's blood on the 64th post-transplant day and the donor's blood. The reactivity was strongest in pre-BMT sera. We conclude that residual antibodies sensitized before BMT are a major cause of these hematological problems.
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PMID:[A case report of multiple-transfused aplastic anemia complicated by hemolysis and delayed neutrophil recovery after bone marrow transplantation]. 157 36

These studies examined the role of cytokines in chronic autoimmune graft-versus-host disease (GVHD) in B6D2F1 mice injected with lymphoid cells from DBA/2 mice. Anti-interleukin (IL)-4 and anti-interferon (IFN)-gamma mAb, or IFN-gamma, were used in vivo to modulate B cell hyperactivity and disease. Kinetic experiments showed that, 2-3 weeks after induction, GVH mice had 100x elevated serum IgE, while IgG1 and IgG2a were 10x above normal. Early treatment with anti-IL-4 mAb or IFN-gamma decreased serum IgE and IgG1 and had no effect on IgG2a. Anti-IFN-gamma mAb treatment increased serum IgE and IgG1 while reducing IgG2a. This increase in serum immunoglobulins could be correlated with an increased spontaneous secretion of IL-4, IL-5, and IL-6 in spleen cell cultures from anti-IFN-gamma mAb-treated GVH mice. While neither anti-IFN-gamma nor IFN-gamma treatments altered the disease course, anti-IL-4 treatment delayed proteinuria and death in GVH mice. These observations suggest an important role for IL-4 in immune complex-mediated glomerulonephritis in chronic GVHD.
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PMID:Effects of in vivo administration of interferon (IFN)-gamma, anti-IFN-gamma, or anti-interleukin-4 monoclonal antibodies in chronic autoimmune graft-versus-host disease. 159 85

Small bowel transplantation is associated with a significant risk of graft versus host disease owing to the large amount of organized lymphoid tissue within the graft. This study assessed whether graft lymphoid cells could persist in the long term following fully allogeneic small bowel transplantation when graft rejection was prevented by cyclosporin immunosuppression. Transplantation was carried out between PVG and DA strains of rat. Cyclosporin (15 mg/kg) was given daily from transplantation, and groups of animals were studied at 28 and 56 days after grafting. The proportions of donor- and recipient-derived cells in the graft and in the host gut and lymphoid tissues were assessed using immunohistochemical tissue staining and monoclonal antibodies specific for cells expressing class I antigens from the two strains of rat. Results demonstrated a persisting population of graft-derived T cells which were capable of migration to the host. Therefore, there may be a long-term risk of graft versus host disease after small bowel transplantation under cyclosporin immunosuppression.
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PMID:Persistence of allogeneic cells in graft and host tissues after small bowel transplantation. 159 24

These data indicate that in rat heterotopic syngeneic SBT, the venous drainage system of the graft has profound effects on cell recovery in the gut-associated lymphoid tissue of both graft and host. Depending on the functional status of the same lymphoid tissue (Gorezynski, personal communication, 1992) one could thus anticipate significant perturbation of host-antigraft (and GVH) reactivity in allogeneic situations according to the venous drainage used. The mechanism(s) responsible for these effects have not been investigated. However, one testable hypothesis is that (a) factor(s) from the gut can control lymphoid recirculation within the mesenteric lymphoid tissue, and that this (these) factor(s) are absorbed under normal circumstances by hepatic tissue.
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PMID:Altered cell trafficking in mesenteric lymphoid tissue following syngeneic heterotopic small bowel transplantation in rodents. 160 61

Four to six weeks after total lymphoid irradiation (TLI), there is a selective deficit in the CD4+ T cells which secrete IL-2, proliferate in the MLR, and induce GVHD (Th1-like functions). A similar deficit in CD4+ T cells which secrete IL-4 and help antibody responses (Th2-like functions) is not observed. In the present study, shielding of the thymus with lead during TLI increased the Th1-like functions of CD4+ cells. Mice without thymus shields showed a marked selective reduction in the medullary stromal cells identified with the monoclonal antibody, MD1, and the severe reduction was prevented with thymus shields. Thus, shielding the thymus prevents the depletion of thymic medullary stromal cells and allows for a rapid recovery of Th1-like functions in the mouse spleen after TLI. Th2-like functions recover rapidly after TLI whether or not the thymus is irradiated.
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PMID:Thymic irradiation inhibits the rapid recovery of TH1 but not TH2-like functions of CD4+ T cells after total lymphoid irradiation. 168 27

Bone marrow transplantation to reconstitute defective hematopoietic cell lines in children with congenital defects is limited by donor availability, graft rejection, and graft-versus-host disease (GVHD). These problems can be eliminated by transplanting normal preimmune fetal hematopoietic stem cells (HSC) into an unrelated preimmune fetal recipient. We show here that injections of allogeneic fetal stem cells into preimmune fetal lambs and monkeys result in long-term stable hematopoietic chimerism. HSCs harvested from the livers of preimmune fetal sheep and monkeys when injected into the peritoneal cavity of young unrelated fetal sheep and monkey recipients results in stable, long-term postnatal hematopoietic chimerism involving lymphoid, erythroid, and myeloid cells of donor origin. Donor cell engraftment was achieved without the use of cytoablative procedures and without the development of GVHD.
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PMID:Hematopoietic chimerism in sheep and nonhuman primates by in utero transplantation of fetal hematopoietic stem cells. 168 May 4

Human fetal liver hemopoietic stem cells were transplanted into preimmune fetal sheep. Significant numbers of recipient fetuses showed evidence of engraftment of human stem cells which responded in vivo to human-specific hemopoietic growth factors. The chimerism has persisted now for > 2 years without significant graft loss. No evidence of GVHD has been noted. Successful engraftment was associated with the expression of human erythroid, myeloid, and lymphoid differentiation. This xenograft model offers useful possibilities for the study of the biology of human hemopoiesis in vivo.
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PMID:Successful stable xenograft of human fetal hemopoietic cells in preimmune fetal sheep. 168 60


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