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 report on our experience with allogenic bone marrow transplantation in the treatment of Fanconi anemia. Eight patients were treated, ranging in age from 5 to 17 years. Beside severe hemopoietic insufficiency, all patients exhibited typical cytogenetic abnormalities with an increased rate of chromosomal breaks, while constitutional signs of the disorder were rather variable. Marrow donors were HLA-identical siblings. For conditioning, we used cyclophosphamide at 5 mg/kg on 4 consecutive days followed by thoraco-abdominal irradiation at 5 Gy with full lung shielding. For prophylaxis of graft versus host disease, cyclosporin A was given except in 3 cases who received T-cell depleted marrow. In 2 of the latter cases, graft failure was observed, successfully reversed in one by retransplantation. All others showed prompt and stable engraftment of donor cells. Complications of graft versus host disease developed in 2, requiring prolonged immunosuppressive treatment. Of 8 transplanted patients, 7 survive. With the exception of a recently treated girl, they have normal stable marrow functions. Our results confirm that successful treatment of Fanconi anemia is possible in a majority of patients with HLA-identical donors.
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PMID:[Treatment of Fanconi anemia by bone marrow transplantation]. 330 84

Late onset transfusion-dependent anaemia is very rare in the presence of sustained engraftment after HLA-identical sibling bone marrow transplantation. The only previously described consistent cause is pyridoxine-responsive sideroblastic anaemia. We describe here a second cause, marrow hypoplasia and fibrosis, occurring in association with extensive chronic graft-versus-host disease (GVHD). A 20-year-old Caucasian male who received cyclophosphamide and fractionated total body irradiation followed by an unmanipulated HLA-identical sibling marrow transplant from his sister for acute nonlymphoblastic leukaemia in first remission developed chronic GVHD of the skin and mouth at day 101 post-transplant. At day 689 post-transplant, he developed leuco-erythroblastic anaemia with thrombocytopenia, due to patchy marrow hypoplasia and fibrosis. Between days 689 and 1987 post-transplant he received 71 units of packed red cells, requiring transfusion approximately monthly. He remains well although still on prednisone for chronic GVHD of skin and is receiving desferrioxamine 4 g five nights/week i.v. as prophylaxis for iron overload.
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PMID:Late onset transfusion-dependent anaemia with thrombocytopenia secondary to marrow fibrosis and hypoplasia associated with chronic graft-versus-host disease. 333 93

Highly purified and cloned preparations of interleukin-1 (IL-1) were found to antagonize the capacity of erythropoietin (Epo) to stimulate the proliferation of mouse spleen and bone marrow erythroid precursor cells (EPC) in culture. Cloned murine IL-1 and purified and cloned human IL-1 alpha and IL-1 beta were approximately equipotent in this assay. IL-1 inhibited the proliferation response of EPC even when added as long as 17 h after Epo, suggesting that IL-1 does not affect binding of Epo to receptors or biochemical events following shortly thereafter. Indomethacin did not influence the inhibitory effect of IL-1 on Epo-induced proliferation, and PGE2 had no demonstrable effect on the process. Tumor-necrosis factor-alpha and interferons beta 1, and gamma did not affect Epo-induced proliferation. It is suggested that IL-1 mediated antagonism of the effects of Epo on erythroid precursors is a factor in the pathogenesis of many types of hypoplastic anaemia, including those associated with infections, rheumatoid arthritis and systemic lupus erythematosus, giant-cell arteritis, graft-versus-host disease and disorders associated with lymphocyte-mediated suppression of erythropoiesis.
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PMID:Inhibition by interleukin-1 of the action of erythropoietin on erythroid precursors and its possible role in the pathogenesis of hypoplastic anaemias. 349 70

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

Marrow transplantation is effective treatment for a number of haematological diseases in patients under the age of 50 who have an HLA-identical sibling donor. It is generally successful when used early in the treatment of aplastic anaemia. It is the only treatment that offers long-term disease-free survival for patients with acute leukaemia who have relapsed at least once, with 10-30 per cent apparent cures. Although still somewhat controversial, it appears also to be the treatment of choice for patients with acute non-lymphoblastic leukaemia in first chemotherapy induced remission and for those with chronic myelogenous leukaemia in the chronic phase since approximately 50-60 per cent of these patients are surviving after marrow transplantation in complete remission, apparently cured. Marrow grafting is the only effective treatment for many patients with inherited immunological-deficiency diseases and certain genetic storage diseases. It is being explored for the therapy of patients with lymphoma, Hodgkin's disease, multiple myeloma, small-cell lung cancer, testicular cancer, ovarian cancer and genetic disorders of haematopoiesis. Cures of congenital Fanconi anaemia, Blackfan-Diamond anaemia, osteopetrosis, and paroxysmal nocturnal haemoglobinuria have been achieved by marrow grafting. Genetic disorders associated with haemolytic anaemia and cyclic neutropenia have been cured by marrow grafting in animals. Target disorders for marrow transplantation in humans are thalassaemia major and sickle cell disease, and, indeed, a first successful transplant for treatment of thalassaemia major has recently been described (Thomas et al, 1982). Marrow transplantation has been limited by the fact that many patients do not have HLA-identical siblings and very few have monozygotic twins. The Seattle team has now explored the use of less well-matched family member donors in more than 80 patients with leukaemia. These donors share one HLA haplotype genetically with the patient and are phenotypically identical at two of the three major HLA loci on the other HLA haplotype (Clift et al, 1979). Overall, the post-transplant survival appears more a reflection of the type and stage of the leukaemia than of the marrow donor. Patients with leukaemia grafted in relapse have a projected survival of 20-30 per cent and those transplanted in remission of 50 per cent. The incidence and severity of GVHD may not be significantly different from that of patients given HLA-identical sibling marrow grafts.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Application of bone marrow transplantation in leukaemia and aplastic anaemia. 635 79

Five patients with Fanconi anaemia have been treated by bone marrow transplantation from HLA identical donors. Only one patient survived for more than 3 years. She is now perfectly healthy with complete haematological reconstitution with chimaerism and disparition of chromosomal abnormalities. In contrast, four patients died of acute severe GVHD soon after grafting. In addition, all had signs of severe cyclophosphamide toxicity. This evolution could be explained by a special sensitivity of FA cells to alkylating agents and may indicate the need to modify the conditioning regimen in FA patients.
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PMID:Bone marrow transplantation in Fanconi anaemia. 700 Jan 53

Sixty-five multiply transfused patients with severe aplastic anemia were given cyclophosphamide followed by grafts anemia were given cyclophosphamide followed by grafts from HLA-identical siblings. The effect of the administration of viable donor buffy coat cells following the marrow inoculum was evaluated with regard to graft rejection and survival. Results in 43 patients so treated are presented along with those in 22 concurrent patients given marrow alone. Most patients given buffy coat had positive in vitro tests of sensitization indicating a high risk for graft rejection, while all but one of the patients given marrow alone had negative tests. Thirty of the 43 (70%) patients given marrow and buffy coat are alive between 10 and 61 mo (median 36) after grafting; 4 died after graft rejection and 6 with acute or chronic graft-versus-host disease (GVHD). Eleven of the 22 (50%) patients given marrow alone are alive between 29 and 65 mo (median 52); 7 died after graft rejection and 3 with GVHD. The addition of buffy coat cell infusions to the marrow inoculum reduced the risk of rejection and increased survival in the currently reported transfused patients when compared to patients grafted before 1976. However, there was an increased risk of chronic GVHD. Recipients of marrow from female donors survived slightly better (73%) than recipients of male marrow (58%).
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PMID:Marrow transplantation with or without donor buffy coat cells for 65 transfused aplastic anemia patients. 703 11

Murine graft versus host (GVH) disease takes two forms depending upon the parental/F1 strain combination employed. Acute lethal GVH disease is characterized by anemia, lymphopenia, hypogammaglobulinemia, profound anti-F1 cytotoxicity, and the loss of cytotoxic potential against third-party alloantigen. In contrast to this, chronic GVH disease is characterized by polyclonal B cell activation, autoantibody production, no anti-F1 cytotoxicity, and retained cytotoxicity against allotargets. We have previously reported that this marked disparity in disease expression results from a radiosensitive host cell which protects the F1 mouse from parental anti-F1 CTX in mice undergoing CGVH disease. Using an in vitro system to induce the host protective cell, we now demonstrate that two distinct Thy-1+ cells emerge which regulate CTX against the host. One cell is of host origin, radiation sensitive, and functionally resembles a veto cell. The second regulatory cell, of parental origin, is radiation resistant and restricted in its ability to suppress anti-F1 CTX. We further demonstrate that the emergence of these cells is modulated by competitive immunoregulatory influences mediated by T contrasuppressor and I-J+ cells.
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PMID:The host response in graft versus host disease. III. The in vitro induction of regulatory cells in chronic murine graft versus host disease. 763 39

Fanconi anemia is a genetic disorder associated with diverse congenital abnormalities, progressive bone marrow failure, and increased risk of leukemia and other cancers. Affected persons often die before 30 years of age. Bone marrow transplantation is an effective treatment, but there are few data regarding factors associated with transplant outcome. We analyzed outcomes of HLA-identical sibling (N = 151) or alternative related or unrelated donor (N = 48) bone marrow transplants for Fanconi anemia performed between 1978 and 1994 and reported to the International Bone Marrow Transplant Registry. Fanconi anemia was documented by cytogenetic studies in all cases. Patient, disease, and treatment factors associated with survival were determined using Cox proportional hazards regression. Two-year probabilities (95% confidence interval) of survival were 66% (58% to 73%) after HLA-identical siblings transplants and 29% (18% to 43%) after alternative donor transplants. Younger patient age (P .0001), higher pretransplant platelet counts (P = .04), use of antithymocyte globulin (P = .005), and use of low-dose (15 to 25 mg/kg) cyclophosphamide plus limited field irradiation (P = .009) for pretransplant conditioning and cyclosporine for graft-versus-host disease prophylaxis (P = .002) were associated with increased survival. Bone marrow transplants are effective therapy for Fanconi anemia. The adverse impact of increasing age and lower pretransplant platelet count on transplant outcome favors earlier intervention, especially when there is an HLA-identical sibling donor.
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PMID:Bone marrow transplantation for Fanconi anemia. 767 Jan 20

Although bone marrow transplantation (BMT) can eliminate the hematologic manifestations of Fanconi anemia (FA), patients are unusually susceptible to complications associated with the use of cyclophosphamide (CY) in the conditioning regimen. To investigate modifications of the conditioning regimen, we reviewed the records of 24 patients with FA who received an allogeneic BMT. All patients presented with severe pancytopenia. One patient was transplanted with overt leukemia as well. Donors were HLA-identical siblings in 22 cases and 1- and 2-antigen mismatched relatives in two cases, respectively. All conditioning regimens included CY 200 mg/kg in 10 patients; 140 mg/kg with or without antithymocyte globulin in 12 and 20 mg/kg with 400 cGy total body irradiation in two. GVHD prophylaxis comprised methotrexate and/or cyclosporine. Only one of 21 evaluable patients did not show signs of engraftment. Toxicities included grade III/IV mucositis in 20 patients, severe dermatitis in four and veno-occlusive disease in four. Acute GVHD (> or = grade II) occurred in nine of 22 patients. Four patients developed chronic GVHD. With a median follow-up time of 24 months, 14 of the 24 patients are alive with normal hematopoietic function. Eight of the 10 patients with matched sibling donors who were conditioned with CY 140 mg/kg are alive and well. We conclude that BMT is an effective treatment for FA. Conditioning regimens using lower doses of CY are associated with manageable toxicity and can potentially increase the survival rate of patients with HLA-matched donors.
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PMID:Bone marrow transplantation for patients with Fanconi anemia: a study of 24 cases from a single institution. 777 21


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