Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The records of 101 patients (64 males and 37 females) registered at Bristol Children's Hospital who died between January 1986 and December 1989 were reviewed to determine the cause of death. Nineteen patients (19%) died without obtaining remission and 6 (6%) in first remission. Seventy-six (75%) died after relapse; three during re-induction and two in second remission. The causes of death were active disease in 85 patients (84%), active disease and infection (4%), active disease and other factors (4%), infection only (3%), toxic cardiomyopathy (2%), graft versus host disease (2%), and second malignancy (1%).
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PMID:Causes of death in a paediatric oncology unit. 131 96

In the decade since the early 1980s, the increasing use of immunosuppressive therapy for cancer and autoimmune disease, as well as for organ transplantation, has combined with the acquired immunodeficiency syndrome epidemic to increase greatly the incidence of opportunistic infections and other complications of the gastrointestinal tract. Consequently, barium fluoroscopic and cross-sectional imaging studies tailored to address these problems are no longer uncommon. Although overlap exists, there are radiographic patterns that can direct the diagnosis to an opportunistic infection and sometimes to a specific pathogen. This article describes and illustrates the radiographic findings of gastrointestinal superinfection with Candida albicans, cytomegalovirus, Cryptosporidium spp, herpes simplex virus, Mycobacterium tuberculosis, M avium-intracellulare, and human immunodeficiency virus. Other gastrointestinal tract complications of immunosuppression are discussed, including graft-versus-host disease following bone marrow transplantation, typhlitis, and pseudomembranous colitis.
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PMID:Gastrointestinal tract in the immunocompromised host: opportunistic infections and other complications. 141 Mar 32

Pneumocystis carinii pneumonitis (PCP) can occur in immunocompromised hosts, especially AIDS and cancer patients. Although recent research has focused on PCP in AIDS patients, few studies have described the clinical presentation of PCP in recipients of bone marrow transplantation (BMT). Between 1976 and 1991, of 1454 BMT patients at the University of Minnesota, PCP was documented in only 19. Eighteen of these had not been receiving PCP prophylaxis. Patients presented with a brief period (2-10 days) of symptoms including dyspnea, cough, and fever in greater than 75% of patients, but had only scant abnormal physical findings. Chest X-rays showed bilateral infiltrates in 58% of all patients, though 15% had no or minimal X-ray findings. Bronchoscopic alveolar lavage confirmed the diagnosis most often, but 13% of lavages were negative and required biopsy for the diagnosis. High dose trimethoprim-sulfamethoxazole was the initial treatment for 84% of the patients though 25% of these patients were later switched to pentamidine due to poor response or hypersensitivity reactions. Despite prompt diagnosis and therapy, overall survival was poor, with only 37% of patients surviving pneumonitis. Patients developing PCP less than 6 months post-BMT had greater mortality (89%) versus only 40% in later onset PCP (p less than 0.0001). Despite this better survival in the late-onset PCP cohort, the development of pneumonitis in these patients underscores the necessity for continued PCP prophylaxis beyond 1 year in some patients. Ongoing immunocompromise and need for prophylaxis should be appreciated in patients with graft-versus-host disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pneumocystis carinii pneumonitis following bone marrow transplantation. 142 81

Autologous bone marrow transplantation (BMT) is a therapeutic option for the treatment of lymphohematopoietic malignancies and solid tumors. Despite the intensive cytoreductive therapy, however, the rates of tumor recurrence after autologous BMT remain unacceptably high. Current studies suggest that the administration of cyclosporine (CsA) disrupts the reconstitution of self-tolerance following autologous BMT leading to the induction of an autoimmune graft-versus-host disease (GVHD). Studies in a rat tumor model and preliminary clinical trials suggest that this autoimmune or autologous GVHD provides a significant antitumor effect. Moreover, the antitumor effect of autologous GVHD can be enhanced by administration of gamma-interferon, which upregulates the antigen recognized by the autoreactive effector cells of autologous GVHD. These studies indicate that the induction of an autoimmune GVHD after autologous BMT may be a promising immunotherapeutic approach for treatment of certain neoplastic diseases.
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PMID:Autologous graft-versus-host disease: a novel approach for antitumor immunotherapy. 142 45

Over the last 20 years allogeneic bone marrow transplantation from an HLA-identical sibling donor has become the treatment of choice for a number of human haematological malignancies, severe aplastic anaemia, some congenital diseases of the immune and haemopoietic systems, and some inborn errors of metabolism. Recently, the successful introduction of HLA-matched unrelated donor transplants, convenient T cell depletion technology, combination immunosuppressive therapy to minimise graft-versus-host disease, blood products that are seronegative for cytomegalovirus, effective antiviral agents, and cloned haemopoietic and immune system growth factors have markedly increased the scope of bone marrow transplantation. Additionally, autologous transplantation appears to have promise especially in lymphoma and breast cancer.
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PMID:Bone marrow transplantation. 144 94

An investigation has been undertaken of 479 deaths occurring up to the end of 1990 among 883 patients diagnosed with non-Hodgkin's lymphoma from 1974 to 1985 who were included in the population based National Registry of Childhood Tumours. The objectives were to perform a descriptive analysis looking particularly at the deaths not directly due to non-Hodgkin's lymphoma, to determine the frequency of the different causes of death and to study the trends over time. Among the 476 patients with sufficient information for the cause of death to be established, these were: non-Hodgkin's lymphoma, 377 (79%); treatment related (other than second primary tumour), 86 (18%); second primary tumour, 10 (2%); and other, three (1%). The proportion of all deaths not directly due to non-Hodgkin's lymphoma increased from 15% for those diagnosed during 1974-6 to 32% for those diagnosed during 1983-5. Among the 86 treatment related deaths, the more precise causes were bacterial infections, 26 (30%); viral and other infection, 14 (16%); metabolic, 19 (22%); renal, eight (9%); anaesthetic related, seven (8%); respiratory, four (5%); cardiac, three (3%); graft versus host disease, three (3%); and other, two (2%). Treatment related deaths from infection accounted for 27 (6%) of all patients diagnosed in 1974-9, and 13 (3%) in 1980-5. Treatment related deaths not due to infection occurred in 23 (5%) of those diagnosed in 1974-9 and 23 (6%) in 1980-5. Five treatment related deaths, including four anaesthetic related deaths, were identified as avoidable. Some of the deaths from metabolic and renal disease may also have been avoidable. Only 11 deaths have been recorded more than five years after diagnosis, six being due to second primary tumours. As follow up is relatively short for patients diagnosed more recently, further deaths from second malignancies and treatment related cardiovascular problems may well occur. A substantial number of children with non-Hodgkin's lymphoma die to treatment related causes. Deaths from infection have decreased in line with the overall improvement in survival rates. Other treatment related mortality has remained constant. Further improvements in survival for childhood non-Hodgkin's lymphoma will depend on maintaining the fine balance between the therapeutic value of intensive treatment and its potential harmful effects.
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PMID:Causes of death in children diagnosed with non-Hodgkin's lymphoma between 1974 and 1985. 147 92

Of 182 consecutive patients undergoing allogeneic bone marrow transplantation (BMT), the relative numbers of those who received red blood cells (RBC), platelets (PLT), and granulocytes were 82%, 96%, and 26%, respectively. The transfused patients received an average of 1.26 (SD +/- 2.0) RBC units, 9.41 (SD +/- 13.2) PLT transfusions, and 0.33 (SD +/- 1.1) granulocyte concentrates per week per 50 kg body wt. in the period starting on the day of bone marrow transplantation (BMT) up to 60 days post BMT. The total number of units per transfused patient was 7.7 (range 1-63) RBC, 55.2 (range 2-394) PLT and 6.2 (range 1-36) granulocytes in the same period. Patients with grades II-IV acute graft-versus-host disease (GVHD) needed more RBC and PLT (p less than 0.001) than patients with grades 0-I acute GVHD. Patients with late engraftment required more granulocyte and PLT transfusion than those with early engraftment (p less than 0.05). Patients with high-risk malignancy had greater need for RBC and PLT than "low-risk patients" (p less than 0.02 and p less than 0.01), respectively). Patients with major ABO-incompatible donors showed a greater need for RBC than patients with minor ABO incompatibility (p = 0.02) or ABO identical donors (p = 0.01). Patients with relatively poor estimated survival required the most RBC and PLT.
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PMID:Blood transfusion in marrow graft recipients. 151 Oct 59

Natural suppressor (NS) cells, which nonspecifically suppress immune responses, are present in the spleen following exposure to radiation, chronic graft-versus-host disease, or cancer and in normal bone marrow. A model system is described which allows the study of cytokines activating and inhibiting NS cells, cytokines mediating NS activity, and NS effects on cytokine synthesis. Recombinant interleukin-3 (rIL-3) and granulocyte-macrophage colony-stimulating factor (rGM-CSF) efficiently activated NS cells present in normal bone marrow and were effective at concentrations as low as 5 U/ml. At high concentrations, GM-CSF, but not IL-3, did not activate NS cells. Recombinant interferon-gamma (rIFN-gamma) blocked the activation of bone marrow NS cells by rIL-3, but did not down-regulate NS cells once activated. The NS cells secreted one or more soluble suppressor factors, which blocked IL-2 synthesis and also inhibited IL-2-dependent T cell proliferation in the presence of excess IL-2.
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PMID:Cytokine regulation of bone marrow natural suppressor cell activity in the suppression of lymphocyte function. 153 70

The observation that malignant cells express antigens that may be recognized by immunocytes and that immune effector mechanisms have the capability of destroying tumor cells has increased our appreciation of the biology of cancer and its relationship to immune function as well as offered new options for therapeutic intervention. Clinical trials are in progress to evaluate several different approaches to modifying the host's immune response against tumor. One approach is to administer agents that have direct activity against the malignancy. For example, antibody conjugates bring cytotoxic molecules of chemotherapy, radioisotopes, or toxins directly to the tumor. A second approach is to administer agents that modulate the host's own antitumor response such as IFN-alpha and IFN-gamma. Adoptive cellular immunotherapy aimed at isolating and expanding the host's own tumor-specific lymphocytes and inducing activation and proliferation with lymphokines such as IL-2 has shown encouraging results. Even though clinical data are still quite premature, it is reasonable to assume that in the future immunomodulation including the stimulation of immune effector mechanisms to eradicate tumor, the reconstitution of immune deficiency in diseases such as AIDS, the suppression of immune function to avoid graft rejection and GVHD, and the isolation and insertion of genes encoding tumor antigens into recombinant vectors to immunize the host to the tumor antigen will be commonly and successfully employed.
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PMID:The role of the immune system in the pathogenesis of cancer. 154 19

The reciprocal translocation (9;22)(q34;q11) is highly characteristic of chronic myeloid leukemia (CML) and the pericentric inversion inv(16)(p13q22) is almost only found in acute nonlymphocytic leukemia of the myelomonocytic subtype (ANLL M4). Only twice before have an inv(16) and a t(9;22) been found in the same cells, and both times the patients seemed to have de novo ANLL M4. We describe the case of a 21-year-old man who in July 1986 presented with a clinically and hematologically classic chronic phase CML. Treatment with busulfan led to no improvement; instead in September 1986 he developed blast crisis with ANLL M4Eo morphology. He was now cytogenetically examined and the karyotype 45,X,-Y,t(9;22)(q34;q11),inv(16)(p13q22) was found. Southern blot analysis of the bone marrow DNA sampled at this time revealed a standard rearrangement in the 3' end of the M-bcr. Intensive cytostatic treatment caused cytopenia followed by complete hematologic, clinical, and cytogenetic reversal to chronic phase CML, so that in January 1987 the bone marrow karyotype was 46,XY,t(9;22)(q34;q11). Persistent splenomegaly was treated with splenectomy, and a chloroma of the skin was removed by irradiation. In March 1987 he received an allogeneic bone marrow transplant. Since then his only medical problem has been mild graft-versus-host disease; he is well and is working full time as a blacksmith.
Cancer Genet Cytogenet 1992 Mar
PMID:Acute myelomonocytic leukemia with inv(16)(p13q22) complicating Philadelphia chromosome positive chronic myeloid leukemia. 155 89


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