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 chronic, debilitating syndrome related to graft-versus-host disease (GVHD) has been recognized in long-term survivors following allogeneic bone marrow transplantation. In six of 20 marrow graft recipients who survived for more than one year after receiving a transplant, this complication developed; they were studied to better define the syndrome. There was no association between the sex of either donor or recipient, HLA type, blood group, conditioning regimen or marrow cell dose and subsequent development of chronic GVHD. All six patients had mild to moderate manifestations of acute GVHD following prompt engraftment. Chronic GVHD was characterized in each patient by progression to scleroderma-like skin involvement with hyperkeratosis, reticular hyperpigmentation, atrophy with ulceration and fibrosis with limitation of joint movement. A sicca syndrome was prominent in five patients. Four patients had idiopathic interstitial pneumonitis. Infectious complications were frequent, and DNA viral infections were prominent. Autoimmune hemolytic anemia was present in three patients, and one patient had antinuclear antibody (ANA). A spectrum of immune abnormalities was observed including hypergammaglobulinemia, immunoglobulin M (IgM) paraprotein, elevated circulating immune complexes, plasma cell hyperplasia, lymphocytotoxic antibodies and autoantibodies to autologous or donor lymphocytes. Despite clinical similarity to collagen vascular diseases, none of these patients had anti-DNA antibodies or antibodies to smooth muscle, thyroid or extractable nuclear antigens. In one patient, a skin graft from the marrow donor remained healthy despite progressive involvement in recipient skin, whereas unrelated skin grafts were rejected. Immunosuppressive therapy and plasmapheresis have not been effective. Four patients have died (median survival 458 days from transplantation). Chronic GVHD appears to be a syndrome of disordered immune regulation features of immunodeficiency and autoimmunity.
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PMID:Chronic graft versus host disease: a syndrome of disordered immunity. 3 1

An 8-year-old boy with a granulocytic sarcoma of the proximal ileum metastatic to mesenteric lymph nodes was placed into complete remission with surgical excision of the primary tumor and conventional induction chemotherapy with daunorubicin and cytosine arabinoside. He was then treated with high dose cytosine arabinoside, fractionated total body irradiation, and allogeneic marrow transplantation from his 22-month-old brother who was completely matched at the major histocompatibility complex. Methotrexate was given following the transplant to prevent graft-versus-host disease (GVHD). His post-transplantation course was complicated by a transient autoimmune hemolytic anemia related to an ABO blood group incompatibility and hepatic fungal microabscesses which responded to Amphotericin therapy. Four years following the transplant the patient remains in complete remission. The prognosis for patients with granulocytic sarcoma has been poor although, perhaps, improved over the past decade. This is the first published case report of successful treatment of a granulocytic sarcoma of the ileum by allogeneic marrow transplantation.
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PMID:Granulocytic sarcoma of the ileum treated by bone marrow transplantation. 202 76

Hematopoietic chimeras were produced at four different stages of ontogeny between two allogeneic strains of chickens. All chimeras produced by parabiosis at day 12 of embryogenesis and the majority (83%) of the ones produced at day 15 by intravenous injection of allogeneic stem cells remained healthy, chimeric, and specifically tolerant at both the humoral and cell-mediated level throughout a long examination period. Chimeras generated at day 17 of embryogenesis demonstrated specific unresponsiveness at the cell-mediated level but produced specific anti-donor alloantibodies directed against erythrocyte-associated major histocompatibility complex (MHC) (B-G) antigens. These chimeras and a minority (17%) of the chimeras generated at day 15 of embryogenesis developed severe antibody-mediated autoimmune hemolytic anemia after the 5th mo of age and succumbed to massive bursal lymphomas and metastases by the 10th mo of age. The immunological and pathological characteristics of these birds appear to reflect an autoimmune state rather than one of tolerance. Erythroid chimeras generated at day 21 of ontogenic development displayed normal levels of GVH reactivity. These birds were eventually able to eliminate the chimeric state and remained healthy until deliberately killed. These results show that there is a critical period in embryogenesis during which the induction of allogeneic erythrocytic chimerism leads to the development, in adult life, of severe autoimmune anemia, B cell lymphomas, and death. B-G MHC antigens are erythroid differentiation antigens of the chicken. Polymorphic determinants on B-G antigens appear to be important cross-reactive determinants (with environmental bacteria), against which a high background immunity exists. Evidence is presented that the immune response to B-G antigens is responsible for the development of autoimmunity and other pathological events that follow and that tolerance to class I MHC antigens (B-F antigens) shared by lymphocytes erythrocytes is maintained at the same time that B-G tolerance is broken.
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PMID:Tolerance and autoimmunity to erythroid differentiation (B-G) major histocompatibility complex alloantigens of the chicken. 612 77

The development of immune-mediated hemolytic anemia is a well-recognized complication after allogeneic bone marrow transplantation (BMT). The majority of reported cases, however, have been alloimmune in origin due to ABO or minor red blood cell antigen incompatibilities between the donor and recipient. In this study, we report seven adult patients who developed autoimmune hemolytic anemia (AIHA) between June 1985 and January 1993. These patients were identified from a total of 236 adult patients who received T cell-depleted (TCD) grafts as graft-versus-host disease (GVHD) prophylaxis. The onset of AIHA was at a median of 10 months (range 7-25 months) post-transplant and occurred in 5% of all patients transplanted with TCD grafts who survived at least 6 months. Six patients had a warm reacting autoantibody, while one patient had a cold-reacting antibody with a thermal amplitude up to 30 degrees C. All were receiving immunosuppressive treatment for GVHD at the time of diagnosis. Initial treatment in all patients consisted of steroids. Three of the seven had a partial response while the four remaining patients failed to respond to corticosteroids. Splenectomy was performed in three patients with two partial responses. Four patients were treated with additional therapeutic interventions, including plasmapheresis, immunoglobulin infusions, staphylococcus protein A column, or other immunosuppressive agents. In five cases, erythropoietin was administered as adjunctive treatment to maintain adequate hematocrit levels. Two patients are presently in complete remission after prolonged courses of steroids, while a third patient has compensated hemolysis requiring low-dose steroids. Four patients died due to either infectious complications or disseminated intravascular coagulation secondary to cold agglutinin disease. These data indicate that AIHA is a clinically significant and not infrequent complication in allogeneic marrow transplant recipients. The response to conventional treatment is generally unsatisfactory as even patients who ultimately remit require prolonged courses of immunosuppressive therapy.
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PMID:Autoimmune hemolytic anemia following T cell-depleted allogeneic bone marrow transplantation. 880 20

Purine nucleoside analogues are a new class of drugs with activity against non-dividing lymphocytes. They should thus play a major role in the treatment of low grade lymphoid malignancies. These drugs have been shown to have strong effect in DNA synthesis on actively dividing cells, mainly through interference with DNA polymerases and ribonucleotide reductase. However, the cell cycle kinetics of low grade lymphocytic lymphomas is characterized by the presence of very low growth fractions. Hence, the action of these drugs in slowly progressing lymphoid malignancies cannot be accounted by the same mechanism observed in actively proliferating tumors and needs to be explained through activity against quiescent resting lymphocytes. Recent work has stressed the role of purine analogues in inducing programmed cell death of quiescent lymphocytes, which could be explained through the induction of accelerated DNA strand breaks. This process leads to consumption of NAD for poly(ADP-ribose) synthesis, which could induce critical depletion of ATP. As this action extends to normal resting lymphocytes deleterious effects related to their immunosuppressive action are also observed, i.e. prolonged lymphopenia predominating in T cells and especially in CD4 subset, increased frequency of opportunistic infections and perhaps increase in autoimmune complications like autoimmune hemolytic anemia. Nevertheless, beneficial effects of this immunosuppressive action have also been reported in the prevention of graft-versus-host disease, graft rejection and in some autoimmune diseases like multiple sclerosis. Work needs to be carried out to define better the mechanisms of action of these drugs on the different immunological effectors, as well as studies in animal models of transplantation and autoimmune diseases.
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PMID:Adverse and beneficial immunological effects of purine nucleoside analogues. 913 60

A 36-year-old woman with RAEB-t and severe bone marrow fibrosis undergoing autologous BMT, developed a histologically documented GVHD-like skin rash. Thereafter, autoimmune thyroiditis, autoimmune thrombocytopenic purpura and autoimmune hemolytic anemia and a lupus anti-coagulant (LAC) were diagnosed. The patient is still alive, symptom-free and in first complete remission (CR); however, all of the autoantibodies are still detectable, with the exception being the anti-erythrocyte antibody. The most outstanding feature of the present case is the polymorphism of the autoimmune events, in the absence of a coexisting systemic autoimmune disease. This patient has achieved long-term disease-free survival (DFS) in first CR despite high-risk MDS and the repeated immunosuppressant therapy required because of the complications described above; a GVL reaction somewhat similar to the autoimmune events may have contributed towards maintaining disease control.
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PMID:Multiple autoimmune events after autologous bone marrow transplantation. 915 54

Recent studies on animal and human autoimmune hemolytic anemia (AIHA) suggest that immunological tolerance loss toward red blood cells (RBC) self-antigens may be originate by different, non-mutually exclusive, mechanisms. According to now available data the identified mechanisms may be: ignorance against RBC self-antigens; molecular mimicry; polyclonal T and/or B cells activation; errors in central or peripheral tolerance; immunoregulatory disorders including cytokine network alteration. In some patients with AIHA, stimulation of PMBC by synthetic Rh peptides indicate that ignorant T and/or B cell clones may recognize cryptic RBC self-antigens. AIHA associated with bacterial or viral infections seems to be produced by polyclonal T and/or B cells activation against foreign antigens which mimic protein or carbohydrate epitopes on RBC. Polyclonal activation of host B cell clones by donor alloreactive T cells causes the AIHA in chronic GVHD. As the tolerance loss is concerned, experiments on mouse lines expressing a transgene with autoantibody activity against murine RBC have shown that non-deleted peripheral B cell clones may produce RBC autoantibodies. In humans a genetic defect of Fas/FasL autoreactive lymphocytes apoptosis may be associated to AIHA. Immunoregulatory disorders due to depletion of CD4+ CD25+ T cells or Th1/Th2 cytokines imbalance may induce autoimmune diseases. In mice AIHA may be induced or improved by cytokines or anticytokine antibodies administration. In NZB/W mice and human AIHA there is an increased production of Th2 cytokines as IL4 and IL10 but INF-gamma reduced production. In addition in human AIHA has been shown a downregulation of IL12 and therefore, an IL10/IL12 immunoregulatory circuit imbalance which might facilitate the RBC autoantibodies production.
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PMID:Mechanisms of immunological tolerance loss versus erythrocyte self-antigens and autoimmune hemolytic anemia. 1456 12

We report a 12-year-old girl who developed nephrotic syndrome 6 months after umbilical-cord-blood transplantation (UCBT) for acute lymphoblastic leukemia (L2). In addition to nephrotic syndrome, she also showed autoimmune hemolytic anemia, thrombocytopenia and gastrointestinal symptoms. Since these symptoms were manifested during the course of tapering immunosuppressive agents, a diagnosis of chronic graft-versus-host disease (GVHD) was made. Findings from a kidney biopsy were compatible with minimal-change disease (MCD), and focal glomerular capillary thrombosis and mild tubular damage were also noted. She was treated with methylprednisolone pulse therapy followed by oral prednisolone. Proteinuria disappeared in 14 days. Gastrointestinal symptoms, anemia and thrombocytopenia were also corrected. This is a case report of nephrotic syndrome as a manifestation of chronic GVHD developed after stem-cell transplantation. A review of the cases reported in the literature is also made.
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PMID:Nephrotic syndrome in a child after umbilical-cord-blood transplantation. 1679 3

Autoimmune hemolytic anemia (AIHA) after allogeneic hematopoietic stem cell transplantation (HSCT) is still not well characterized. The aim of this study was to analyze the incidence and risk factors for the development of AIHA, as well as its prognosis and response to treatment in a series of patients undergoing allogeneic HSCT at a single institution. Between 1996 and 2004, 272 adult patients with a variety of malignant hematopoietic disorders underwent allogeneic HSCT. Direct antiglobulin testing was performed in routine pretransfusion compatibility testing or after clinical suspicion of AIHA. Twelve patients developed AIHA after HSCT at a median time of 147 days (range, 41-170). The 3-year cumulative incidence of AIHA was 4.44%. Eight cold antibodies and four warm antibodies were detected. Multivariate analysis shows that HSCT from unrelated donors (P=0.02) and the development of chronic extensive graft-versus-host disease (GVHD) (P=0.0004) were the only independent factors associated with AIHA. Two patients are still alive. AIHA was never the primary cause of death but added morbidity in patients with other concomitant complications. Patients undergoing HSCT from unrelated donors and those who develop chronic extensive GVHD are especially predisposed for this complication.
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PMID:Autoimmune hemolytic anemia following allogeneic hematopoietic stem cell transplantation in adult patients. 1735 45

An update is provided on monoclonal antibodies (MAbs): concept, production, indications for the diagnosis and treatment of neoplastic diseases and autoimmune disorders, prevention of transplant rejection, and treatment of allergic diseases, autoimmune disease and other noninflammatory disorders such as coronary disease. Mention is also made of MAb use in the prevention of respiratory syncytial virus (RSV) infection. A more extensive account is provided of the use of MAb in B cell lymphomas (anti-CD20) and T cell leukemias (anti-IL-2 R). Likewise, mention is made of the use of MAbs in autoimmune disorders, such as anti-TNF-alfa in application to chronic arthritis, Crohn's disease and psoriasis, anti-C5 in the treatment of chronic arthritis, uveitis, systemic lupus erythematosus, and autoimmune hemolytic anemia. Anti-KT 3 MAb is used to treat acute rejection and graft versus host disease, while anti-IL-2 R alfa and anti-IL-2 R gamma are used for the prevention of acute transplant rejection. Anti-IgE MAb (omalizumab) is used to treat asthma and allergic rhinitis refractory to other treatments. Anti-L5 (mepolizumab), anti-IL-4, anti-TNF and anti-inflammatory cytokine mediator MAbs all have indications in asthma and severe allergic rhinitis, and in intense atopic dermatitis refractory to other treatments. As to the MAbs used for the prevention of RSV infection, mention is made of anti-epitope A of the F protein of the virus.
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PMID:Monoclonal antibodies in pediatrics: use in prevention and treatment. 1766 23


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