Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.1.1.69 (BMT)
2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of MHC class I and subgroups of class II antigens by keratinocytes and enterocytes has been investigated in patients receiving autologous and allogeneic bone marrow transplants. Allogeneic recipients with graft-versus-host disease (GVHD) expressed all the class II antigens HLA DR, DP and DQ more frequently than pretransplant patients, autologous or allogeneic recipients without GVHD post-BMT (p less than 0.01). Staining for DP and DQ was never detected without DR being present. Whenever there was a lymphocytic infiltrate in the epidermis or single cell necrosis in the gut, DR was expressed on the epithelium. There was no difference in class I expression in GVHD. This study further increases the immunopathological characterization of acute GVHD which may improve the understanding of its pathogenesis.
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PMID:Expression of MHC class I and II antigens by keratinocytes and enterocytes in acute graft-versus-host disease. Newcastle Bone Marrow Transplant Group. 265 8

This article has outlined the special problems associated with evaluation of bone marrow before and after BMT. Marrow grafting has become a major form of therapy in oncology and hematology whose potential is only beginning to be fully realized. The transplantation of healthy hematopoietic and lymphoid cells has made possible the use of otherwise superlethal doses of radiation and chemotherapy in preparing the patient for engraftment. In the case of tumors, this allows massive doses of tumorocidal therapy prior to rescue with a BMT. In the case of aplastic anemia, it allows massive immunosuppression and ablation of the residual host marrow in preparation for replacement by the healthy donor marrow. The complications of this procedure include the toxicity of chemotherapy and irradiation upon the liver, lung, and gut as well as less serious toxicity to skin and other organs. The double barrier associated with marrow transplantation consists of rejection and GVHD. Marrow graft failure occurs by two distinct mechanisms, graft resistance and graft rejection. The former is marked by a total failure of any evidence of engraftment and the latter by engraftment followed by disappearance of the graft. GVHD is the immunologic attack upon host tissues by donor lymphoid cells (predominantly mature T cells). In the acute phase, it attacks liver, skin, and gut, with the latter producing the most life-threatening syndrome. Chronic GVHD resembles scleroderma. Treatment of GVHD includes the use of prednisone, cyclosporin A, ATG, and monoclonal antilymphoid antibodies. Prevention includes the attempt to remove T cells from the donor marrow with monoclonal antibodies using complement-mediated cytolysis and other approaches such as conjugation of antibodies to ricin and other toxins. GVHD also produces severe immunosuppression in and of itself added to that produced by chemoirradiation therapy. As a result, the marrow transplant recipient is extremely susceptible to infections. During the early period, the patient is granulocytopenic and susceptible to bacterial and fungal infections, which are dealt with by antibiotics and isolation procedures. Later, viral infections become very important, particularly CMV and other herpes viruses. The relative success in dealing with bacterial and, to some extent, viral infections has brought fungal infections to the fore as major causes of death, especially in higher risk categories of patients. Hemorrhage is a frequent complication owing to delayed megakaryocyte engraftment and thrombocytopenia during the early period and is a serious problem in patients with GVHD of the gut.
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PMID:Pathology of bone marrow in transplant recipients. 306 26

Complete microbial decontamination (laminar air flow room, sterile nursing and oral administration of cefamandole, gentamicin and nystatin) was carried out in 65 consecutive patients prior to allogeneic BMT for leukaemia (n = 58) or aplastic anaemia (n = 7). Very few microorganisms persisted during the post-transplant treatment period, and the gut became sterile in all except for Candida in 11 patients. Six uncomplicated septicaemias, all with persistent organisms simultaneously present in the mouth (Pseudomonas 3, Serratia 1, Candida 2) occurred during a total of 1,360 days with granulocyte counts less than 0.5 X 10(9)/l. Post-transplant fever occurred in 52 patients, exceeding 40 degrees C in 25. Guided by the surveillance cultures only 46% of 43 unexplained febrile reactions were treated with systemic antimicrobials. Significant acute graft versus host disease (AGVHD) occurred in 14 (27%) of 52 patients receiving standard prophylaxis and HLA-matched grafts; immunosuppressive treatment was needed in 8 cases (16%). Thus, the additional costs of total microbial decontamination appear partially regained by a decreased morbidity and a reduced need for antimicrobial and immunosuppressive treatment, although neither fever nor AGVHD could be prevented.
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PMID:Strict protective isolation in allogenic bone marrow transplantation: effect on infectious complications, fever and graft versus host disease. 310 49

Experimental transplantations of cadaver bone marrow (BMT) in beagle dogs were performed to evaluate the problems and potentials in a preclinical setting. The effectiveness of selective decontamination of the gut (SD) and gnotobiotic surveillance in preventing infections during longer aplastic periods was investigated. Three groups of dogs were compared. Group A: controls. Group B: dogs with BMT, without SD and irregular gnotobiotic surveillance. Group C: dogs with BMT, with SD and regular gnotobiotic surveillance. The intestinal colonization of normal healthy beagles shows similarities as well as dissimilarities to the human intestinal microflora. Aerobic potentially pathogenic organisms do not colonize the gut of healthy beagles under our keeping conditions. SD resulted in a significant decrease in infections with Escherichia coli and Plesiomonas. Infections with anaerobes, as well as bacterial infections of the respiratory tract were, however, not prevented. The intestinal colonization in dogs of group C with Clostridium difficile is another obvious effect of SD. The infections encountered during the study indicate the importance of the "take" for the clinical significance and outcome of intestinal colonization with potentially pathogenic organisms. In order to reduce the drug burden of BMT patients, we consider the elimination of routine SD after BMT not to be superior to gnotobiotic surveillance and germ-specific short term decontamination.
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PMID:Infections after experimental cadaver bone marrow transplantation in beagle dogs. Transplantations with and without selective gastrointestinal decontamination. 328 36

To study the impact of the composition of the bone-marrow graft on engraftment and graft-versus-host disease (GvHD), we analyzed the data on 29 patients with acute leukemia in remission and 11 patients with aplastic anemia. All of them received bone-marrow grafts from HLA matched, MLC nonreactive, sibling donors, were nursed in laminar down-flow isolators with selective gut decontamination, and received GvHD prophylaxis with methotrexate. The number of nucleated cells in the marrow graft/kg body weight of the recipient had no relation with the rapidity of engraftment or with the occurrence and severity of GvHD. The number of hematopoietic progenitor cells (CFUc)/kg had a weak, but significant, correlation with both the number of neutrophils at day 30 post BMT and with the day at which the reticulocytes passed the 10% level. The number of T cells/kg did not show any correlation with either the occurrence or the severity of GvHD. Our data show that the concentration of hematopoietic progenitor cells in the graft correlates with the rapidity of engraftment. However, within the range of numbers of T cells infused in this study, no correlation is present between T cells in the graft and GvHD. Therefore, nearly complete depletion of marrow grafts of T cells is probably necessary to effectively decrease the incidence of GvHD.
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PMID:The impact of the composition of the bone marrow graft on engraftment and graft-versus-host disease. 636 14

Seventy-one patients with moderate to severe acute GVHD after BMT were analysed retrospectively. At the start of therapy 96% of the patients had rashes, 45% liver abnormalities and 54% gut dysfunctions. Forty-four patients (62%) had been treated for grade I GVHD with systemic corticosteroids. First therapy for moderate to severe acute GVHD was with corticosteroids (n = 59), psoralen with ultraviolet light (PUVA) (n = 14), cyclosporin (CsA) (n = 10), antithymocyte globulin (ATG) (n = 7), methotrexate (MTX) (n = 2), monoclonal antibodies (n = 1) or thalidomide (n = 1). In 18 of these patients two or more agents were combined. Resolution of skin disease and evaluable liver and gut disease were seen in 48%, 44% and 47% of cases, respectively. Overall complete resolution was seen in 37%. Thirty-two patients received a second treatment, resulting in complete resolution in 31%. Patients with a complete response had an actuarial transplant-related mortality of 37% compared with 82% or worse for patients with other outcomes (p < or = 0.003). Combined treatment was superior to ATG, but not better than corticosteroids. In multivariate analysis a low total sum severity score was the only factor associated with complete response (p = 0.02). AML diagnosis (p = 0.01) and GVHD of the liver (p = 0.02) were independent risk factors for treatment failure.
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PMID:Treatment of moderate to severe acute graft-versus-host disease: a retrospective analysis. 785 35

Infant botulism is a rare disease caused by the release of toxin produced in the intestinal tract by Clostridium botulinum. The disease primarily affects infants under 1 year of age. We report a 3-year-old child with stage IV neuroblastoma who developed symptoms of progressive motor weakness, bulbar palsy and respiratory failure 42 days after autologous BMT. The diagnosis of infant botulism was established by identifying botulism toxin in the stool. Human botulism immune globulin (HBIG) was administered. Following the diagnosis, the patient made significant recovery over the next 7 weeks and was successfully extubated from mechanical ventilation. However, her neuroblastoma eventually recurred and she subsequently died of progressive disease. Although the etiology of the development of infant botulism in this case following autologous BMT still remains unclear, alteration of the intestinal microbial environment from gut sterilization and laminar airflow room isolation or, alternatively, immune suppression during pre- and post-autologous BMT and activation of endogenous spores may have contributed to the development of this disease. The use of HBIG in children with botulism over 1 year of age may be beneficial.
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PMID:Development of infant botulism in a 3-year-old female with neuroblastoma following autologous bone marrow transplantation: potential use of human botulism immune globulin. 819 79

A 3-year old child with juvenile chronic myeloid leukaemia received a T cell-depleted BMT from a male unrelated donor. There was early graft failure associated with increasing splenomegaly and hypersplenism. Splenectomy was performed 53 days post-transplant and was followed by autologous marrow recovery with return of leukaemia. A second unrelated donor BMT was performed 9 months later using T cell-replete marrow from a similarly matched female donor. Grade 2 GVHD involving the skin and gut responded to treatment with steroids. Chimaerism was assessed using Y-specific polymerase chain reaction (PCR) and microsatellites. Samples taken at the time of splenectomy showed no donor marrow engraftment but there was significant engraftment in the spleen. Following the second transplant, donor-type haematopoiesis was documented using a panel of microsatellite probes. The patient remains well 6 months after transplant. Splenectomy should be considered prior to transplant in patients with significant splenomegaly and hypersplenism. Partial chimaerism in the spleen, but not bone marrow, post-BMT, has not previously been documented. PCR technology is a useful and highly sensitive way to assess chimaerism post-BMT and is informative in sex-matched cases, whilst the small amount of material required is advantageous in paediatric patients.
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PMID:Successful second unrelated donor BMT in a child with juvenile chronic myeloid leukaemia: documentation of chimaerism using the polymerase chain reaction. 843 16

The first 25 BMTs at the Royal Liverpool Children's Hospital (Alder Hey) were performed between April 1987 and July 1991. The aim of this report is to evaluate selective decontamination of the digestive tract (SDD) during the first post-BMT month in this series of 14 allografts and 11 autografts. SDD is a method used to abolish carriage of potentially pathogenic microorganisms including yeasts, Staphylococcus aureus and Gram-negative bacilli (GNB). Chlorhexidine mouth wash was used to decontaminate the oropharynx, and neomycin, colistin (polymyxin E) and nystatin (NEOCON) were given to eradicate gut carriage. Oropharyngeal decontamination was successful in 48% of patients, gut carriage was abolished in 60%, and eradication of the carrier state at both sites was achieved in 33%. A septic response was seen in 76% of children and 36% developed septicaemia (indigenous Gram-positive cocci only). A low carriage index for the target microorganisms during the study manoeuvre of SDD was associated with negative blood cultures (p < 0.01). Acute GVHD occurred in 28% of allografts, but was seen in none of the successfully decontaminated children (p < 0.05). It is concluded that septicaemia from yeasts and GNB, but not the septic response, were successfully prevented by SDD.
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PMID:Microbial carriage, sepsis, infection and acute GVHD in the first 25 BMT at the Royal Liverpool Children's Hospital. 848 74

The purpose of this open-label, prospective study was to compare steady state concentrations and clearances of intravenously administered cyclosporine or tacrolimus with and without concomitant high-dose (400 mg/day) fluconazole in allogeneic BMT patients. Twenty-one patients were evaluable. The mean steady state cyclosporine and tacrolimus concentrations without fluconazole were 320.3 and 18.2 ng/ml and increased to 389.2 and 21.2 ng/ml, respectively, after the addition of fluconazole, corresponding to a 21% (P=0.031) and 16% (P=0.125) increase. The mean steady state clearance of cyclosporine and tacrolimus without fluconazole was 6.82 and 1.28 ml/min/kg, which decreased to 5.57 and 1.10 ml/min/kg with fluconazole, corresponding to a 21% (P=0.031) and 16% (P=0.125) decrease, respectively. The 21% difference in the cyclosporine concentration and clearance was not thought to be clinically significant. These results suggest that fluconazole's interaction with cyclosporine or tacrolimus may be a result of fluconazole's inhibition of gut metabolism, resulting in a greater extent of absorption.
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PMID:Evaluation of the drug interaction between intravenous high-dose fluconazole and cyclosporine or tacrolimus in bone marrow transplant patients. 861 Apr 30


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