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)

We have used thalidomide in a rat major MHC mismatch model of graft-versus-host disease (GVHD). When given prophylactically, most animals do not develop GVHD and those developing mild GVHD respond to continued therapy. Treatment of established acute GVHD, likewise, was successful. In both prophylactic and therapeutic administration, animals did not develop GVHD after drug cessation. Animals were shown to be stable chimeras by acceptance of donor strain skin grafts and mixed lymphocyte cultures (no response to donor or recipient strain while responding to third party strain). Treatment of chronic GVHD in this model has shown thalidomide to be better tolerated and more successful than cyclosporine (CSA) or prednisone plus azathioprine. The mechanism of action of thalidomide has been explored using a fluorescent thalidomide derivative. These studies have shown striking similarities between thalidomide and CSA. Both drugs appear to allow the development of antigen specific suppressor cells while inhibiting the development of precursor cytotoxic cells. Because of these encouraging results, we have begun a phase I/II trial of thalidomide in refractory GVHD. The preliminary results are encouraging.
Bone Marrow Transplant 1988 Sep
PMID:Thalidomide for treatment of graft-versus-host disease. 305 47

Thymus tissue implants, thymic epithelial cells obtained from third party donors sharing one HLA-A and -B locus with the recipient, or the thymic hormones thymosin fraction 5 and thymopentin were given to recipients of HLA-identical sibling bone marrow to prevent chronic graft-versus-host disease (GVHD) and accelerate immunologic reconstitution. The clinical courses of 17 patients receiving thymus tissue and 18 patients receiving thymic hormones were reported initially 5 years ago and showed no difference in the incidence of chronic GVHD or immunologic recovery from those of concurrent or historical controls. We report here for the first time nine new patients who received thymus tissue implants with modifications of the culture method to lower the number of lymphocytes in the transplanted tissue with the intent of reducing rejection of the thymus tissue grafts. The clinical outcomes and immunologic functions of these nine patients were similar to those of the recipients of the earlier thymus tissue implants. With follow-up now ranging from 2.2 to 12.3 years (median 6.7) for the total group, 16 patients are alive. Seven never developed chronic GVHD. Nine were treated for chronic GVHD, seven of whom recovered and are leading normal lives, one has chronic pulmonary insufficiency, and one is disabled from chronic GVHD. We conclude that thymus tissue grafts or thymic epithelial cells partially HLA-matched to the recipient, thymosin fraction 5, or thymopentin used as described were not effective in reducing the incidence of chronic GVHD, improving immunologic recovery, or altering long-term survival.
Bone Marrow Transplant 1988 Sep
PMID:Use of thymic grafts or thymic factors to augment immunologic recovery after bone marrow transplantation: brief report with 2 to 12 years' follow-up. 305 51

Between February 1984 and August 1987, 10 patients with severe aplastic anemia were treated with bone marrow transplantation from HLA-identical sibling donors after preparation with cyclophosphamide (CY) 200 mg/kg and total lymphoid irradiation (TLI) 750 cGy. Ages ranged from 5 to 28 years (median 14 years). All patients were previously transfused. Median number of transfusions was 16 (range, 3-886). For post-transplant immunosuppression all patients were given cyclosporine and the last three patients received additional immunosuppression with short-term methotrexate. All patients had initial engraftment and survived for more than 3-46 months after transplantation. One patient developed significant acute graft-versus-host disease (GVHD) and three of nine recipients who survived more than 100 days developed chronic GVHD. One male patient who had received 21 transfusions from his marrow donor before transplantation suffered from persistent granulocytopenia. Otherwise all have Karnofsky performance scores of 90-100%. Although the number of patients is small, it appears that allogeneic bone marrow transplantation with the regimen of CY + TLI for preparation combined with cyclosporine (+ short-term methotrexate) for post-transplant immunosuppression is a promising modality for treatment of previously transfused patients with severe aplastic anemia.
Bone Marrow Transplant 1988 Sep
PMID:Use of cyclophosphamide and total lymphoid irradiation combined with cyclosporine in bone marrow transplantation for transfused severe aplastic anemia. 305 53

Mixed chimerism may occur more frequently than previously thought following allogeneic bone marrow transplantation and may have implications in terms of relapse, graft-versus-host disease and immune reconstitution. DNA analysis using single or multilocus polymorphic probes cannot reliably discriminate between donor and recipient cells below a level of 10%. We used probe pHY2.1, a cloned segment of tandemly repeated DNA (2000 copies) on the long arm of chromosome Y. A dot blot procedure allowed us to immobilize DNA directly from 50 microliter of peripheral blood or bone marrow. Cross-reactivity was eliminated by hybridization at conditions of extreme stringency (65 degrees C, 50% formamide). Mixing experiments detected male DNA at a level of 0.1% after 10 h exposure. Five patients were studied serially post-bone marrow transplantation. One patient showed mixed chimerism for 12 months, one had complete autologous recovery and the remaining three showed complete engraftment. All results were verified by standard karyotyping on bone marrow cells. This technique is a simple, rapid and sensitive assay for chimerism following sex mismatched bone marrow transplantation.
Bone Marrow Transplant 1988 Sep
PMID:A rapid dot-blot assay to assess chimerism following sex-mismatched bone marrow transplantation. 305 54

Gastrointestinal complications following bone marrow transplantation are common and may result from the conditioning regimen, immunosuppression, graft-versus-host disease, or a combination of these factors. These effects may be acute (mucositis, enteritis, esophagitis) or delayed (xerostomia, stricture formation) in onset. We describe here a case of esophageal stricture developing within 1 month of allogeneic bone marrow transplantation.
Bone Marrow Transplant 1988 Sep
PMID:Acute esophageal stricture after bone marrow transplantation. 305 56

Experimental models of chronic graft-versus-host disease have been advocated for studying the pathogenesis of scleroderma. However, microvascular abnormalities have not been documented in these models, whereas in man, cutaneous microvascular pathology (demonstrable by intravital microscopy) is a common feature of scleroderma. In our study scleroderma-like skin disease was evoked by allogeneic bone marrow transplantation in rats. Intravital microscopy of the skin of these animals showed strongly dilated capillaries, resembling the dilated loops in patients. This finding demonstrates that chronic graft-versus-host (scleroderma-like) disease may be pertinent to study the pathogenesis of microvascular injury in scleroderma.
J Rheumatol 1988 Sep
PMID:In vivo demonstration of microvascular pathology by intravital microscopy in experimental chronic graft-versus-host disease: analogy with scleroderma. 305 70

We evaluated retrospectively the incidence and prognosis of bacteremias after bone marrow transplantation treated in protected environment with intestinal decontamination. Bacteremias are more frequent during the extreme granulopenia (55% of the patients) than during recovery of granulocyte counts greater than 500/mm3 (35% of the patients). Gram + organisms are more frequently responsible of bacteremias (80%), mainly Staphylococcus epidermidis and Streptococci. Mortality is low (7%) and related to additional factors like GVH, resistant leukemia. These data invite to develop new approaches of prevention of bacterial infection, with measures possibly efficient on Gram + organisms.
Pathol Biol (Paris) 1988 Sep
PMID:[Bacteremias after bone marrow grafts in a protected environment: effects, various aspects and prognosis]. 305 71

We explored the immunoincompetence of mice undergoing a chronic graft-vs-host reaction (GVHR) across minor histocompatibility barriers. BALB/c and B10.D2 mice are H-2d and mls b, and differ only with regard to minor histocompatibility antigens (MiHA). A large number of BALB/c mice were unirradiated or were irradiated with 300, 600, or 900 R. They then were injected with 5 X 10(7) spleen cells from either allogeneic B10.D2 or syngeneic BALB/c mice. The spleen cells from these recipient mice were assayed at various times post-irradiation/injection for their proliferative response to Con A and LPS, their ability to suppress the mitogen responses of normal spleen cells, and for the genetic specificity of this suppression. Spleen cells from BALB/c mice that had received 600 or 900 R (but not 0 or 300 R), and allogeneic B10.D2 lymphocytes, became very hyporesponsive to mitogens and became suppressive in vitro by days 7 to 10 post-irradiation/injection. These phenomena persisted for the entire 49 days of the experiment. After an initial period of splenomegaly, the spleens of these mice gradually became depleted of viable lymphocytes. Initial characterization of suppressor cells found in the spleens of GVH mice showed that they were not removed by treatment with anti-Thy-1.2 plus complement. GVH suppressors also were not adherent to plates coated with antiserum directed towards murine Ig. In addition, these cells did not adhere to plastic plates. Thus, we believe that the suppressor cells found in mice undergoing GVHD across MiHA are not mature T cells, B cells, or macrophages, but belong to a class of suppressor cells termed natural suppressor (NS). Genetic analysis of NS cell activity showed that as early as 10 days post-irradiation/injection, NS cells inhibited mitogen responses of all mouse strains tested, the exception being the relative difficulty in suppressing the LPS response of B10.D2 (syngeneic with donor cells). By day 42, this had developed into an almost complete inability to suppress a B10.D2 LPS response, although at this time NS cells were still capable of inhibiting all the other mitogen responses of all strains tested, including the Con A response of B10.D2 spleen cells. Moderate amounts of mitogen unresponsiveness and suppressor activity were seen in the syngeneic groups (BALB/c----BALB/c) but only if recipients received 600 or 900 R. This was a transient phenomenon that was maximal at day 14, and which we believe to be a similar but less severe degree of immunoincompetence when compared with that seen with allogeneic stimulation in the B10.D2----BALB/c GVH model.(ABSTRACT TRUNCATED AT 400 WORDS)
J Immunol 1985 Sep
PMID:Graft-vs-host reactions (GVHR) across minor murine histocompatibility barriers. II. Development of natural suppressor cell activity. 316 Jul 74

We have been studying the mitogen hyporesponsiveness and immunosuppression induced in chronic murine graft-vs.-host disease (GVHD) induced across minor histocompatibility (MiHA) barriers. In this system, donor and recipient mice are major histocompatibility complex- and mls-identical, and are nonreactive in primary mixed leukocyte reactions. Spleen cells from B10.D2 (H-2d, mls b) mice were injected into irradiated (600 rad) BALB/c (H-2d, mls b) recipients. Recipient spleen cells are hyporesponsive to mitogens, and contain natural suppressor (NS) cells. We investigated the cellular requirements for both the in vivo induction and the in vitro expression of this GVH suppression. T cells are required in the graft, but they are not sufficient to induce suppression, and a non-T cell population is also required for maximum induction in vivo. T cells are also required for the maximum expression of NS cell suppressive ability in vitro. Early in the course of GVH, the suppressor cells are able to suppress the Con A and LPS response of all mouse strains tested (except for the relative difficulty in suppressing the B10.D2 LPS response). Later, they become almost completely unable to suppress the B10.D2 LPS response; while still being able to suppress the Con A and LPS response of all other strains tested (including the B10.D2 Con A response). This inability to suppress a B10.D2 LPS response can be brought back to almost complete suppression by the addition of concanavalin A supernatant (CAS). We present a hypothesis to explain what may be a common mechanism for GVH-induced suppression, total lymphoid irradiation-induced suppression, and neonatal tolerance. These situations all include rapidly proliferating lymphohematopoietic stem cell populations, and also have large numbers of NS cells. NS cells can suppress proliferating lymphoid populations, and their development and activity are greatly enhanced by T cell signals such as are supplied by donor T cells in chronic GVHD. Thus, NS cells may feed back on and downregulate self-reactive T cells or T cells responding to introduced foreign antigens.
J Exp Med 1985 Sep 01
PMID:Synergism between T and non-T cells in the in vivo induction and in vitro expression of graft-vs.-host disease-induced natural suppressor cells. 316 77

We compared the immunologic and metabolic effects of systemic (i.e., caval) versus portal venous drainage of small-intestinal allografts in rats. Survival times in either unidirectional rejection or graft-versus-host disease models were not significantly altered by the route of venous drainage. Portoportal and portacaval isografts and controls were then pair-fed after transplantation. After 6 weeks of pair-feeding, weight gain, plasma amino acid concentration, and the histologic appearance of the liver were similar among the three groups. Hepatic protein synthesis was greater in pair-fed rats with portoportal isografts, although this difference disappeared in the fasted state. Our data suggest that there is little immunologic or metabolic advantage of portal versus systemic venous drainage of small-intestinal allografts in rats. Because the latter is technically simpler, it may be preferable in small-bowel transplantation.
Surgery 1988 Sep
PMID:Immunologic and metabolic effects of caval versus portal venous drainage in small-bowel transplantation. 326 96


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