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)

Antithymocyte and antilymphocyte globulins (ALG) are currently used as immunosuppressive agents in organ transplantation and for the treatment of acute graft-versus-host disease and aplastic anemia. Since any type of immunosuppressive treatment is known to carry the risk of developing B-cell lymphoproliferative disorders, we investigated the in vitro effect of ALG on human B-cell activation and proliferation. The data demonstrate that whatever the source of lymphocytes used for ALG preparation (thymocytes, thoracic duct lymphocytes, B- or T-cell lines), (1) ALG react with both B- and T-cell lines, and (2) ALG contain antibodies specific for B cells (eg, CD21) or common to T and B cells (eg anti-beta 2-microglobulin, anti-HLA-DR, CD18, CD11a) in addition to T-cell-specific antibodies. Unlike all other T-cell mitogens tested (Concanavalin A [Con A], Pokeweek mitogen [PWM], CD3 and CD2 antibodies), ALG do not trigger B-cell differentiation into immunoglobulin-secreting cells at concentrations which induce maximum T-cell proliferation. This effect could be attributed to a direct interaction of ALG with B lymphocytes as shown by the capacity of ALG to block the response of purified B cells to a variety of activators. Furthermore, all the ALG tested were shown to inhibit the proliferation of six of the seven Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines and six of the seven Burkitt's lymphoma cell lines studied. This selective B-cell antiproliferative property of ALG was not reproduced with CD11a, CD18, CD21, CD24, or anti-HLA-DR monoclonal antibodies (MoAbs). These results suggest that, although suppressing T-cell responses, ALG treatment may directly control B cell proliferation to some extent, in keeping with the relatively low risk of posttransplant lymphoproliferative disorders reported with ALG.
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PMID:Antiproliferative effect of antilymphocyte globulins on B cells and B-cell lines. 156 43

Seventy-one patients with hematologic malignancies received bone marrow from a histocompatible sibling (n = 48) or a partially matched relative (n = 23) that had been depleted of CD5+ T cells with either an anti-CD5 mooclonal antibody (MoAb) plus complement (anti-Leu1 + C) or an anti-CD5 MoAb conjugated to ricin A chain (ST1 immunotoxin [ST1-IT]). These patients received intensive chemoradiotherapy consisting of cytosine arabinoside, cyclophosphamide, and fractionated total body irradiation. Both anti-Leu1 + C and ST1-IT ex vivo treatments effectively depleted bone marrow of T cells (97% and 95%, respectively). Overall, primary and late graft failure each occurred in 4% of evaluable patients. The diagnosis of myelodysplasia was a significant risk factor for graft failure (P less than .001), and if myelodysplastic patients were excluded, there were no graft failures in major histocompatibility complex (MHC)-matched patients and 2 of 23 (8.7%) in MHC-mismatched patients. The actuarial risk of grade 2 to 4 acute graft-versus-host disease (GVHD) was 23% in MHC-matched patients and 50% in MHC-mismatched patients. In MHC-matched patients, acute GVHD tended to be mild and treatable with corticosteroids. Chronic GVHD was observed in 6 of 36 (17%) MHC-matched patients and none of 11 MHC-mismatched patients. There were no deaths attributable to GVHD in the MHC-matched group. Epstein-Barr virus-associated lymphoproliferative disorders were observed in 3 of 23 MHC-mismatched patients. The actuarial event-free survival was 38% in the MHC-matched patients versus 21% in the MHC-mismatched patients. However, if outcome is analyzed by risk of relapse, low-risk patients had a 62% actuarial survival compared with 11% in high-risk patients. These data indicate that the use of anti-CD5 MoAbs can effectively control GVHD in histocompatible patients, and that additional strategies are required in MHC-mismatched and high-risk patients.
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PMID:Selective depletion of bone marrow T lymphocytes with anti-CD5 monoclonal antibodies: effective prophylaxis for graft-versus-host disease in patients with hematologic malignancies. 171 80

Epstein-Barr virus (EBV) lymphoproliferative disease is seen in patients with both congenital and acquired immunodeficiencies. Lymphoproliferative disease has been reported in 1 to 3% of renal transplant recipients. Most patients presented with solid tumor masses, rather than an infectious mononucleosis-like syndrome. About one third of cases had involvement of the renal allograft with tumor; the small intestine or central nervous system was also frequently affected. About half of the patients survived. The most frequent therapy used for survivors was decreasing the dose of immunosuppressive therapy and surgical resection of lymphoproliferative lesions. Compared with fatal cases, survivors more often had evidence of active EBV infection (primary or reactivated), received cyclosporine as the major immunosuppressive agent, had polyclonal lesions, and had B-cell hyperplasia rather than lymphoma. Lymphoproliferative disease has been described in 5 to 13% of heart transplant recipients. In our review, the cardiac allograft was not involved by disease in any patient; however, the lungs were involved in more than half of the cases. The soft tissues were frequent sites of lymphoproliferative disease. All patients had lymphoma or immunoblastic sarcoma on pathology and all had monoclonal lesions. While only 8% of patients survived, about half died from causes unrelated to lymphoproliferative disease. EBV lymphoproliferative disease has been reported in 9% of heart-lung transplant recipients. Most of the patients presented with pulmonary symptoms and the pulmonary allograft was involved in 80% of cases. The large and small intestine were frequently affected. About 60% of patients survived; survivors were treated with acyclovir and decreases in the dose of immunosuppressive drugs. Lymphoproliferative disease has been described in 2% of liver transplant recipients. In our review, the hepatic allograft was involved in one third of cases; the tonsils, kidneys, and small intestine were frequently affected. Half of the patients survived; survivors were most often treated with reduction in immunosuppressive therapy and surgical resection of lesions. Compared with fatal cases, survivors had fewer organs involved and fewer monoclonal lesions. Lymphoproliferative disease has been reported in 1 to 2% of bone marrow transplant recipients. Use of T-cell depleted bone marrow and infusion of anti-T-cell antibodies to prevent graft-versus-host disease increased the risk of EBV lymphoproliferative disease. In our review, the bone marrow was involved by lymphoproliferative disease in one third of cases; the liver, spleen, kidney, and lungs were frequently affected. About 16% of patients survived; 2 survivors were treated with infusions of monoclonal anti-B-cell antibodies and 1 received interferon alpha.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Epstein-Barr virus lymphoproliferative disease associated with acquired immunodeficiency. 184 44

Natural killer lymphocytes can spontaneously kill in vitro a variety of malignant cultured cells. NK cells are present in all normal individuals, and in some species (human, rats) present peculiar morphological features (large granular lymphocytes). They are usually lacking conventional T or B markers, but it appears likely that most NK cells actually are poorly mature cells belonging to the T cell lineage. The physiological control of NK activity is complex. A major role seems to be devoted to the production of interferon. The physiological roles of NK cells are still unknown: they might participate in the control of cell differentiation, in peculiar of hematopoietic precursors and thymocytes; they probably play a role as defense mechanisms during the first days of viral infections; they might be involved in bone-marrow allograft rejection and in acute graft-versus-host disease. However, their actual role in anti-tumor surveillance remains controversial, especially in humans. Nevertheless, NK cells might play some role in the surveillance against leukemias and lymphomas. NK cell defects could participate in the increased occurrence of lymphoproliferative disorders observed in immuno-suppressed patients.
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PMID:[Natural killer lymphocytes. Their role in pathology]. 315 60

We conclude that the most common secondary cancers which develop after marrow transplantation are lympho-proliferative disorders and solid tumors. The consequences of the secondary malignancies are serious, with more than 90% of the patients with non-Hodgkin lymphomas associated with EBV infection and more than 75% of the patients with solid tumors dying despite treatment. Secondary leukemia developing in donor T-s is rare, but was fatal in all cases. EBV infection plays a major role in leading to the non-Hodgkin lymphomas in a setting of immune dysregulation from ATG or anti-T-cell monoclonal antibody treatment of acute GVHD. Other factors are also important for development of non-Hodgkin lymphoma and include T-cell depletion of donor marrow and HLA-mismatching between donor and recipient, known to lead to dysregulation of T-lymphocyte function. These factors set up an environment of proliferative stimuli which cannot be controlled by the recovering immune system, setting the stage for a secondary cancer. The role of irradiation is becoming more prominent in association with solid tumors, particularly in aplastic anemia patients conditioned with irradiation. The final event of tumor expression is most likely the result of a cascade of events, perhaps initiated with the conditioning regimen or with stimuli to proliferation, which, after later signals, leads to malignant transformation. For lymphoproliferative disorders, the time of latency is shorter than for solid tumors, suggesting a different molecular mechanism. The incidence of oncogene expression or mutation in tumor suppressor genes in these solid tumor patients has not been investigated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Secondary malignancies after marrow transplantation for leukemia or aplastic anemia. 780 95

There is a well documented risk of late infection following both splenectomy and bone marrow transplantation. In asplenic patients, the phagocytic and antibody producing roles of the spleen are lost and there is a lifelong susceptibility to infection which may be overwhelming and fatal. Patients most at risk are children, those with underlying lymphoproliferative disorders and those receiving immunosuppressive therapy. Although it is hard to prove benefit from preventative strategies, patients are likely to benefit from prophylactic antibiotic therapy and from immunisation with pneumococcal, Haemophilus influenzae-B and meningococcal vaccine given prior to splenectomy. Following an allogeneic bone marrow transplant (BMT), recovery of immune function takes up to a year. During this time, patients are at high risk from cytomegalovirus (CMV) and varicella zoster virus (VZV) infections and also from pneumocystis pneumonia. Prophylactic medications are used to good effect. The major threat of late infection occurs in patients with chronic graft versus host disease (cGVHD)--there is increased susceptibility to bacterial, fungal and viral infections. Many patients without cGVHD recover immune function fully and many develop antibodies to specific recall antigens. This does not occur in all patients and although there is a low risk of infection with organisms against which vaccines are available. If it is not possible to measure specific antibody titres and consequently offer selective re-immunisation, then a universal vaccination strategy should be in force. Response to vaccines is likely to be poor before one year post BMT. For autologous transplant recipients, immune recovery is probably complete and routine re-immunisation is not likely to offer much benefit. For both asplenic and bone marrow transplant patients, education of patient and physician is important.
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PMID:Prophylaxis against late infection following splenectomy and bone marrow transplant. 781 19

Gastrointestinal (GI) disease is frequent in all types of immunocompromised patients but occurs with greatest frequency in patients with acquired immunodeficiency syndrome (AIDS). Thus, much of this review deals with human immunodeficiency virus (HIV)-related GI diseases. Gastrointestinal diseases in other immunocompromised patients are compared with those in patients with AIDS. Conditions unique to transplant recipients, such as graft-versus-host disease (GVHD) and posttransplant lymphoproliferative disorders (PTLDs), are discussed separately. We have divided these GI diseases into four main categories: (1) HIV-related inflammatory conditions other than opportunistic infections (HIV-related enteropathy, proctocolitis, and CD8 lymphocytosis); (2) inflammatory conditions unrelated to HIV or opportunistic infections (neutropenic enterocolitis, regional enteritislike enteropathy, and GVHD); (3) opportunistic infections (illnesses caused by herpesvirus, cytomegalovirus, and miscellaneous other viruses; Mycobacterium, Candida, Histoplasma, Cryptococcus, Cryptosporidium, Microsporida, Isospora, Leishmania, Toxoplasma and Strongyloides organisms as well as Pneumocystitis carinii; and (4) neoplasias (Kaposi's sarcoma [KS], AIDS-related non-Hodgkin's lymphoma [NHL], HIV-related Hodgkin's disease [HD], PTLDs, and miscellaneous neoplasms). The prevalence, pathogenesis, clinical manifestations, gross pathological findings, and microscopic features of each disease entity are discussed.
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PMID:Gastrointestinal disease in the immunocompromised patient. 795 57

Today, bone marrow transplantation (BMT) is an established therapy. This statement is best verified by the number of BMTs performed. Between January 1990 and December 1992, 172 European teams in 26 countries carried out a total of 14,334 transplants. There were 6642 allogeneic transplants: 5513 BMT from an HLA-identical sibling donor, 370 from a non-identical family member, 88 from an identical twin donor and 671 from an unrelated volunteer donor. There were 7692 autologous transplants: 6577 autologous bone marrow, 777 peripheral-blood stem-cell and 338 combined bone-marrow and peripheral-blood stem-cell transplants. Indications were: leukaemias in 52% (7479), lymphoproliferative disorders in 29% (4125), solid tumours in 11% (1540), aplastic anaemia and thalassaemia in 3% (487) and inborn errors an miscellaneous disorders in the remaining 5% (703). The results of these transplants are not yet known. From previous analyses it can be expected that more than 50% of patients will be alive and well 10 years after BMT. The main factors influencing outcome are known; they depend on type, sub-type, stage of disease at time of transplant, the time from diagnosis to transplant and the conditioning regimen for all transplants. For allogeneic BMT, donor source, donor and recipient age, sex, donor/recipient sex combination, donor and recipient viral status, graft-versus-host disease prevention method and region are additional factors. Knowledge of these factors enables us today to estimate the potential risk and adjust the therapy for an individual patient.
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PMID:Bone marrow transplantation today. 815 55

Review of liver biopsy or autopsy material from 33 patients with severe combined immunodeficiency or combined immunodeficiency and four patients with DiGeorge syndrome revealed a wide range of hepatic pathology. The most common abnormality was graft-versus-host disease (16 patients), followed by viral infection (4 patients had adenovirus hepatitis, 3 had cytomegalovirus hepatitis). Centrilobular fibrosis with or without veno-occlusive disease was seen in five patients. Three patients had nonspecific hepatitis, four had changes attributed to total parenteral nutrition, and two had lymphoproliferative disorders involving the liver. Both patients with lymphoproliferative disorders had received transplants. Two patients had resolving necrosis probably secondary to non-A, non-B hepatitis. One had atypical mycobacterial infection. Hemosiderosis was a common nonspecific abnormality, seen in nine patients. All patients with hepatic graft-versus-host disease had received transplants or nonirradiated blood products. Hepatic graft-versus-host disease varied in severity from hepatic necrosis with destruction of both large and small bile ducts in a transfusion-associated case to subtle damage to interlobular bile ducts. Even minimal bile duct changes correlated with the clinical impression of graft-versus-host disease in these patients. Late chronic graft-versus-host disease was not seen in any patient, although acute graft-versus-host disease sometimes occurred late after transplant.
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PMID:Pathology of the liver in severe combined immunodeficiency and DiGeorge syndrome. 837 33

The role of allogeneic sibling BMT for children with Wiskott-Aldrich syndrome is established. Mismatched T cell-depleted BMT has been successful, although significant problems with graft rejection, GVHD, and post-transplant lymphoproliferative disorders have been reported. We have performed four BMTs for children with Wiskott-Aldrich syndrome utilizing phenotypically HLA-identical unrelated donors. A non-TBI (total body irradiation) conditioning regimen was utilized, and BM was not T cell-depleted. All patients engrafted and developed significant, although manageable, GVHD. All patients are alive 3+ to 17+ months post-transplant. These results suggest that matched unrelated donor BMT has a definite role in the treatment of Wiskott-Aldrich syndrome.
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PMID:Unrelated donor BMT for Wiskott-Aldrich syndrome. 840 61


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