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)

Immunotoxicity studies have been performed on the photosensitizing agent Photofrin II (PHFR), a porphyrin derivative used in photodynamic therapy. Hybrid CD2F1 (H-2d/H-2d) or inbred C57Bl/6 (H-2b) male mice were injected with graded doses of the agent (from 1.2 to 12 mg/Kg ip) on day -5, -3 and -1 before assays. The animals, or spleen cells collected from them on day 0 with respect to PHFR treatment, were tested for: a) competence of producing GVHD upon cell transfer into allogeneic, immunosuppressed recipients; b) graft response against challenge with allogeneic lymphoma cells; c) delayed-type hypersensitivity (DTH) against sheep red blood cells; d) in vitro response to mitogens; e) NK cell activity; f) in vitro generation of alloreactive cytotoxic T lymphocytes (CTL); g) resistance against the challenge of a sublethal dose of Pseudomonas aeruginosa. Moreover the LD50 of the drug given ip has been determined in male CD2F1 mice. The results show that PHFR, even at the highest doses used, does not affect most of the immunological parameters studied, except for a marginal inhibition of CTL generation and increment in proliferative responses to Con A or LPS. These data along with parallel studies performed by our group on human models in vitro, showing increased susceptibility of PHFR-treated tumors to NK or LAK effector cells, point out that PHFR, in the absence of systemic photoactivation, is essentially non-immunotoxic in vivo and could render tumor cells more susceptible to natural immunity.
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PMID:Experimental studies of immunotoxicity of a photosensitizing agent (Photofrin II) in mice. 147 18

Immunotoxins are a new class of antitumor agents consisting of tumor-selective ligands (generally monoclonal antibodies [MoAbs]) linked to highly toxic protein molecules that have been modified to remove their normal tissue-binding domains. These immuno-conjugates combine the potency of the parent toxin with the specificity of the attached ligand. Toxins used in the construction of immunotoxins belong to a group of peptides that catalytically inhibit the elongation step of protein synthesis, and include ricin, abrin, pokeweed antiviral protein, gelonin, Pseudomonas exotoxin A, diptheria toxin, and alpha-sarcin. To synthesize immunotoxins, the normal cell-binding function must be removed by chemical cleavage or modification, or in the case of toxins that have been cloned, genetic engineering used to delete amino acids critical to cell binding. Covalent linkage of toxin to ligand generally involves a disulfide or thioether bond, though recently, recombinant toxin molecules with ligands that are genetically engineered into the protein have been made. The most successful clinical application of immunotoxins has been in the depletion of T cells from allogeneic bone marrow grafts to prevent graft-versus-host disease (GVHD). Clinical trials have been conducted using immunotoxins for the systemic treatment of chronic lymphocytic leukemia (CLL), GVHD, and selected solid tumors. With the possible exception of GVHD, responses have been limited. Obstacles have included rapid systemic clearance, poor delivery to extravascular tumor deposits, and humoral immune responses to the immunotoxin. Research to overcome these problems is in progress and should lead to a better definition of the role of immunotoxins in the therapy of malignancies.
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PMID:Immunotoxins: a clinical review of their use in the treatment of malignancies. 268 83

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

At our Division of Hematology eight clinical studies were performed using ceftazidime alone or in combination with other antibiotics. In the first randomised study ceftazidime (45 patients) proved to be statistically superior (p less than or equal to 0.05) to the combination of cefotaxime and gentamicin (45 patients). The poor results of the latter combination - 49% clinical responses compared with 71% for ceftazidime - have been confirmed by the EORTC study group of Klastersky (1). The second study aimed at 30 patients who failed to respond to cefotaxime and gentamicin. All bacteriologically documented infections were cured with ceftazidime. The clinical response rate was 73%. In the third randomised study we compared ceftazidime plus flucloxacillin in 49 patients in order to extend the spectrum to resistant staphylococci with a ceftazidime monotherapy (51 patients). The addition of flucloxacillin did not improve the results substantially. The overall clinical response rate was 81% with the combination and 85% with ceftazidime alone. In the fourth study on 23 patients with allogenic bone marrow transplantations, receiving cyclosporin A as prophylaxis against graft versus host disease, no nephrotoxic effect was observed. The fifth study comprised 20 patients over 65 years of age, in whom no toxicity different from younger patients was seen. In the sixth study with 51 patients per group we compared ceftazidime with the combination ceftazidime plus cephalothin. This study demonstrated an increased efficacy of the combination against Staphylococcus epidermidis and proved that two different cephalosporins, given simultaneously, are not antagonistic. Analysis of 34 Pseudomonas septicaemias in the seventh study with a clinical success rate of 94% demonstrated clearly the potency of ceftazidime against this particularly dangerous organism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Results of several different controlled studies with ceftazidime in the treatment of infections in immunosuppressed patients]. 331 29

Four adult patients with acute non-lymphocytic leukemia were given marrow grafts from HLA-identical siblings following 120 mg/kg cyclophosphamide and 10-12 Gy total body irradiation. All received intermittent intravenous methotrexate as prophylaxis against graft-versus-disease (GVHD). In an attempt to accelerate immune recovery and prevent GVHD, each patient received thymopentin (TP5) for 100 days after grafting. No adverse effects were seen with TP5 administration. All four patients developed acute GVHD (one grade I, one grade II, and two grade III). Two patients died of late infections: one at 6 months from Pneumocystis carinii pneumonia and one at 11 months from disseminate Pseudomonas, Candida and cytomegalovirus infection. Two patients survive more than 3.9 years after transplantation with Karnofsky scores of 100%. One required treatment for chronic GVHD and recovered. Delayed-type hypersensitivity, antibody production to specific antigen in vivo, and results of in vitro immunologic studies were not altered by TP5 treatment. We conclude that while the administration of TP5 in these patients as described was not harmful, it did not prevent opportunistic infection, improve immunologic reconstitution or lower the incidences of acute or chronic GVHD from that of our previous experiences without thymopentin.
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PMID:Treatment of marrow graft recipients with thymopentin. 333 44

A 23-year-old woman gravely ill with Pseudomonas septicemia secondary to presumed drug-induced bone marrow aplasia received marrow transplantation from two male HL-A identical sibling donors. She had a successful engraftment with excellent but temporary clinical improvement. Subsequently she succumbed to graft-versus-host disease manifested by Pseudomonas and Candida albicans septicemia, cytomegalovirus pneumonitis, three phases of dermatitis, nausea, vomiting, dysphagia, diarrhea, fever, edema and bone pain, with gradual but complete graft suppression by the 74th day after the transplantation. A second marrow transplant on the 70th day was unsuccessful.
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PMID:Bone marrow transplantation in a patient with drug-induced aplastic anemia. 440 93

We report the cases of 3 patients with marked dyspnea and an obstructive ventilation disorder associated with chronic graft-versus-host disease after allogeneic bone marrow transplantation. This disorder was characterized by recurrent pulmonary infections and colonization of the lower respiratory tract by Pseudomonas aeruginosa. Two patients have shown rapidly progressive deterioration with death following due to respiratory failure. Intensive therapy with antibiotics, bronchodilators, high-dose steroids, and azathioprine was not effective in arresting the malignant course of this disorder.
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PMID:Obstructive lung disease after allogeneic bone marrow transplantation. 636 98

Bacterial pneumonia as an important complication of bone marrow transplantation (BMT) has not been subjected to comprehensive analysis. Two hundred fifty-five consecutive allogeneic and autologous BMT recipients, ranging in age from 1 month to 53 years, were prospectively followed for 3 days to 3 years (median, 108 days) for development of bacterial pneumonia. Etiology, place acquired, chest radiography, and outcome were recorded and the association between bacterial pneumonia and demographic and clinical variables was analyzed. Thirty-seven (15%) patients experienced 52 episodes of bacterial pneumonia: onset of 13 episodes occurred within 30 days after transplantation, 10 episodes occurred on days +31 to +100, and 29 episodes occurred thereafter. Bacterial pneumonia was the terminal event or contributed to fatal outcome in 8 patients (22% of bacterial pneumonia cases, 3% total study population). Mortality due to hospital-acquired pneumonia (6/21) was significantly higher than (P = 0.03). Bacterial pathogens were identified in 27 (52%) episodes. During the first 100 days after BMT, hospital-acquired Gram-negative bacteria predominated, caused mainly by Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter lwoffi, and Enterobacter cloacae. After day +100, community-acquired, Gram-positive bacteria predominated, particularly Streptococcus pneumoniae. Haemophilus influenzae occurred periodically. Considering all episodes, significant association was found between bacterial pneumonia and veno-occlusive disease (VOD) (P < 0.01) and chronic graft-versus-host disease (GVHD) (P < 0.02). For culture-positive episodes, the association between bacterial pneumonia and VOD was significant (P < 0.001) and borderline for acute GVHD (P = 0.07). It is concluded that VOD and GVHD are positively associated with post-BMT bacterial pneumonia. Its incidence, etiology, risk factors, and outcome are important considerations in its prevention and treatment.
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PMID:Bacterial pneumonia in recipients of bone marrow transplantation. A five-year prospective study. 757 Sep 75

We sent a questionnaire to 22 teams performing allogeneic and autologous bone marrow transplants (BMT) in the UK enquiring about routine use of prophylactic antimicrobials post-transplant, use of CMV-negative blood products and the incidence of major infection acquired more than 3 months post-BMT. Eighteen centres (82%) responded. To prevent Pneumocystis infection 17 centres routinely gave cotrimoxazole at various doses for periods varying between 3 and 12 months (or sometimes longer if chronic GVHD was present) and six centres gave nebulised pentamidine to patients intolerant of cotrimoxazole. Six centres gave penicillin for 1-3 years to allograft patients. Thirteen centres gave only CMV-negative blood products to CMV neg/neg patients, one centre gave CMV immunoglobulin and five centres continued acyclovir to 6 months. During the period 1986-90, 818 autologous and 1007 allogeneic BMT patients were reported, of whom 113 (6.2%) developed severe infections requiring readmission to hospital. The commonest infections were CMV (n = 19), Pneumocystis (n = 12), Pneumococcus (n = 15), Pseudomonas (n = 7) and Aspergillus (n = 8). Some patients with severe infections were not receiving 'appropriate' prophylaxis. Only two of the patients with Pneumocystis were taking cotrimoxazole. We conclude that the duration of continuing prophylaxis against Pneumocystis and pneumococcal infections after BMT needs careful consideration; prophylaxis may be especially important in patients with persisting immune suppression.
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PMID:Life-threatening infections occurring more than 3 months after BMT. 18 UK Bone Marrow Transplant Teams. 799 40

One hundred forty-seven patients with hematologic diseases and treated by allogeneic marrow transplants received graft-versus-host disease (GVHD) prevention with methotrexate and cyclosporine. In addition, 73 of the 147 patients were randomized to receive methylprednisolone during the first 35 days after transplant to improve GVHD prevention, whereas 74 patients were randomized not to receive methylprednisolone. The randomized trial enabled us to examine whether methylprednisolone increased the risk of infection after marrow grafting. Charts of study patients were analyzed retrospectively for infection events including bacteremia, septicemia, and fungemia. The randomization was stratified by diagnosis, patient age, genotypic HLA identity, and assignment to laminar airflow room isolation. All patients were given a short course of methotrexate (no longer than 11 days) and cyclosporine for no longer than 180 days after marrow transplantation. Methylprednisolone was begun on the day of marrow grafting at a dose of 1 mg/kg body weight intravenously in divided AM and PM doses through day 22. Methylprednisolone was administered at a dose of 0.5 mg/kg in divided doses from days 22 through 35, and then discontinued. Infections were analyzed for the time interval ending on day 65 after transplantation, which included the period of methylprednisolone administration and 1 month thereafter. Seventy-one episodes of first infection events were observed in patients receiving methylprednisolone compared with 47 episodes in patients not receiving the drug. Predominant infections were bacteremias, followed in descending order by fungemias and septicemias. The most prevalent organisms cultured were gram-positive bacteria, especially coagulase-negative Staphylococcus and Streptococcus species. Pseudomonas species were the most common gram negative bacteria, and the most prevalent fungus was Candida albicans. Multivariable Cox regression analysis showed that patients receiving methylprednisolone had a 1.5 times higher risk of infection (P = .03), with acute GVHD being another independent risk factor for infections (P = .005). Methylprednisolone, when added to GVHD prevention by methotrexate and cyclosporine, increases the risk of infection during the early posttransplantation period.
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PMID:Increased risk of infection in marrow transplant patients receiving methylprednisolone for graft-versus-host disease prevention. 804 48


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