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)

Viral infections are one of the major complications after bone marrow transplantation, with high mortality and morbidity. Fourty-six patients between 3 and 48 years old (median 15 years) received orally 400 mg (under age 6, 200 mg) acyclovir 4 times daily from day -12 before to day 84 after BMT. All patients were isolated in laminar-airflow units for at least 23 days with total enteral decontamination. They were concomitantly treated with anti-CMV-hyperimmunoglobulin and cotrimoxazol. During acyclovir prophylaxis seven patients had herpes simplex virus infections, all of them were seropositive before BMT. Acyclovir plasma concentrations were measured by use of a new HPLC method. No acyclovir was present (detection limit 40 ng/ml) in the plasma of five out of six patients with HSV infections. Three of them had non-compliance, and a lack of acyclovir absorption developed in two patients under conditioning regimen. No drug-related side effects were observed. Laboratory tests did not show liver or renal toxicity. Take and hematologic reconstitution were unchanged. In our study, oral acyclovir reduced the incidence of herpes simplex infections after bone marrow transplantation. Herpes infections only occurred in patients with non-compliance or lack of acyclovir absorption.
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PMID:[Oral prophylaxis of herpes infections using acyclovir following bone marrow transplantation: a clinical and clinico-pharmacological study]. 242 15

The influence of pretransplant herpes virus antibodies in patients and donors in the subsequent development of chronic graft-versus-host disease (GVHD) was analysed in 150 consecutive HLA identical bone marrow recipients. The Cox regression bivariate analysis showed that (i) pretransplant seropositivity for cytomegalovirus (CMV) in the patients and the donors, (ii) donor seropositivity for herpes simplex virus and Epstein-Barr virus, (iii) high donor and patient age, (iv) a previous grade II-IV acute GVHD, (v) patients receiving unirradiated donor buffy coat cells post-transplant, (vi) overall CMV infection, (vii) high donor herpes virus load (positive serology for 3-4 herpes viruses versus 0-2), and (viii) high recipient herpes virus load prior to BMT were all associated with a high incidence of chronic GVHD. In Cox regression multivariate analysis, high pretransplant donor herpes virus load (p less than 0.001) and a previous grade II-IV acute GVHD (p = 0.02) were the strongest predictors of chronic GVHD. Thus, herpes virus immune cells in the donated marrow may play a role in the pathophysiology of chronic GVHD.
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PMID:Pretransplant herpes virus serology and chronic graft-versus-host disease. 255 36

Oral mucosal ulceration complicating bone marrow transplantation interferes with patients' comfort, nutrition and may lead to systemic infection derived from the mouth. The mucosal injury results from epithelial damage due to the cytotoxic effects of chemotherapy and radiation conditioning as well as from superficial oropharyngeal infection. Because chlorhexidine gluconate is a broad spectrum topical antimicrobial which has been demonstrably effective in preventing oral infection and gingivitis, we performed a randomized, placebo controlled, double-blind trial of chlorhexidine as a mouth rinse in BMT recipients to study the severity of oral mucositis and both oral and systemic infectious complications. One hundred patients were randomly assigned to receive either chlorhexidine gluconate 0.12% mouth rinse or placebo three times daily from the initiation (day -8) of chemoradiotherapy conditioning until day +35 post-BMT. Chlorhexidine use resulted in a trend toward improved oral hygiene index (reduced dental plaque) (p = 0.06) but did not modify the oral mucositis. Patients using chlorhexidine developed a maximum ulceration of 18 +/- 22% of their oral mucosa, while placebo patients ulcerated 25 +/- 31% of the mouth. Ulcerative mucositis was significantly worse in adults compared with children, in individuals who received methotrexate for graft-versus-host disease prophylaxis, and was most prominent on non-keratinized epithelium. Overall, there was no clinically demonstrable additional therapeutic advantage to the use of chlorhexidine in either reducing the mucositis, controlling oral pain, facilitating oral nutrition, shortening hospital stay, or reducing oral infection with herpes simplex virus. There was a trend toward diminished oral candidiasis in chlorhexidine users (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oropharyngeal mucositis complicating bone marrow transplantation: prognostic factors and the effect of chlorhexidine mouth rinse. 264 92

Oral mucous membrane lesions were studied in 54 children below 12 yr of age treated with allogeneic bone marrow transplantation mainly because of hematological malignancies. Sixty-two percent of the children exhibited a wide range of oral side effects during therapy. Lesions observed during the first 2 wk prior to engraftment of the donor marrow were related to the chemo- and radiotherapy given. Oral ulcerations were seen in 34% of the children. Children given methotrexate as graft-versus-host disease (GVHD) prophylaxis exhibited oral ulcerations significantly (P less than 0.05) more often than those given cyclosporin. Oral lesions related to acute GVHD were only observed in two patients. Reactivating herpes simplex virus infection was seen in 35% of the children who were seropositive prior to BMT. An extensive oral candidiasis was observed in 15% of the patients. All six children with a chronic GVHD exhibited changes in the oral mucosa 2-4 yr after transplantation such as erythma of the mucous membranes, tongue atrophy and also lichenoid changes in the buccal mucosa.
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PMID:Oral mucous membrane lesions in children treated with bone marrow transplantation. 266 86

Infections by herpesviruses are common phenomena in patients being treated for acute leukemia and those undergoing bone marrow transplantation. Reactivation of endogenous latent virus caused by the immunosuppressive and cytotoxic effects of cytoreductive therapies is a common mechanism of infection. With cytomegalovirus (CMV), acquisition of exogenous virus by transfusion of blood products containing virus and from the bone marrow graft in the case of bone marrow transplantation can occur. Serious morbidity can result and occasional mortality. CMV infections in allogeneic BMT recipients have high case fatality rates. Treatment and preventive strategies for herpes simplex virus (HSV), CMV, and varicella zoster virus (VZV) have been developed to reduce morbidity. Acyclovir, either given prophylactically or as treatment of active infection, has been highly successful in reducing illness from HSV and VZV infection. For CMV, provision of CMV-seronegative blood products is the mainstay of prevention of morbidity in seronegative patients and is especially important in the care of patients undergoing allogeneic BMT. Ganciclovir given either prophylactically or as early therapy for patients detected to be shedding CMV appears to be a promising strategy. Bolstering host immunity through augmentation of anti-CMV cytotoxic T-cell responses appears to be an exciting candidate therapy under development.
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PMID:Viral infections in leukemia and bone marrow transplant patients. 812 23

A 41-year-old recipient of matched unrelated BMT acquired a severe mucocutaneous herpes simplex virus (HSV) type I infection during acyclovir prophylaxis. He was subsequently treated with high-dose acyclovir, but the HSV infection continued. In vitro analysis of the HSV isolate, obtained before and after the administration of high-dose acyclovir, demonstrated marked resistance to acyclovir but sensitivity to the antiviral agent foscarnet. The mucocutaneous HSV infection healed completely to a 16 day course of foscarnet. However, relapse of the acyclovir-resistant HSV infection occurred 202 days after the first foscarnet treatment but he responded again to a second foscarnet course. These data indicate that, with the rising frequency of acyclovir-resistant HSV infections observed in immunocompromised hosts, viral isolates should be tested for susceptibility to different antiviral drugs in recipients of BMT with recurrent or persistent HSV infections.
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PMID:Successful foscarnet therapy for acyclovir-resistant mucocutaneous infection with herpes simplex virus in a recipient of allogeneic BMT. 838 96

In allogeneic bone marrow transplantation (allo-BMT), donor lymphocytes play a central therapeutic role in both graft-versus-leukemia (GvL) and immune reconstitution. However, their use is limited by the risk of severe graft-versus-host disease (GvHD). Eight patients who relapsed or developed Epstein-Barr virus-induced lymphoma after T cell-depleted BMT were then treated with donor lymphocytes transduced with the herpes simplex virus thymidine kinase (HSV-TK) suicide gene. The transduced lymphocytes survived for up to 12 months, resulting in antitumor activity in five patients. Three patients developed GvHD, which could be effectively controlled by ganciclovir-induced elimination of the transduced cells. These data show that genetic manipulation of donor lymphocytes may increase the efficacy and safety of allo-BMT and expand its application to a larger number of patients.
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PMID:HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. 920 27

In allogeneic marrow transplantation (BMT), donor lymphocytes play a central therapeutic role in both graft-versus-leukemia and immune reconstitution. However, their use is limited by the risk of severe graft-vs-host disease (GvHD). Different strategies have been investigated to obtain all the benefits derived from donor lymphocytes while avoiding the risk of GvHD. In the first pilot study, infusions of donor lymphocytes transduced with the Herpes Simplex virus thymidine kinase (HSV-tk) suicide resulted in anti-tumor activity in 50% of patients. Acute GvHD could be effectively controlled by ganciclovir-induced elimination of the transduced cells. If these results will be confirmed in larger studies, genetic manipulation of donor lymphocytes will increase efficacy and safety of allogeneic marrow transplantation.
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PMID:Suicide-gene-transduced T-cells for the regulation of the graft-versus-leukemia effect. 970 65

We previously demonstrated that severe graft-versus-host disease (GvHD), associated with the therapeutic infusion of donor lymphocytes after allogeneic marrow transplantation (BMT), can be efficiently controlled by the SFCMM-2-mediated expression of the herpes simplex virus thymidine kinase (HSV-tk) suicide gene into the allogeneic lymphocytes. This was achieved by selective elimination of transduced lymphocytes by ganciclovir (GCV) infusion. Despite the positive results of the pilot clinical trial, two vector-related limitations were observed. The induction of a strong immune response against genetically modified cells was observed in two patients. In addition, the only patient who developed chronic GvHD showed only partial response to ganciclovir treatment. In an attempt to overcome these limitations, we developed a new generation of vectors. The neomycin resistance (neoR) gene was removed from the SFCMM-3 and SFCMM-4 retroviral vectors. These vectors are less immunogenic and able to confer higher ganciclovir sensitivity to transduced human lymphocytes. All the vectors carry a modified form of the low-affinity nerve growth factor receptor cDNA, as cell surface selectable marker (deltaLNGFR). The vectors were compared in terms of gene transfer efficiency, and ability to confer high and specific sensitivity to ganciclovir. The SFCMM-3 vector, carrying the entire HSV-tk gene driven by the LTR promoter, allows efficient transduction of human T lymphocytes and confers the highest GCV sensitivity to transduced lymphocytes with a high and a low proliferation index. The expression of the deltaLNGFR marker allows an easier in vitro manipulation and a faster immune selection of transduced cells compared with neoR selection. Finally, the elimination of the neoR gene removes a potent immunogen from transduced lymphocytes.
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PMID:Herpes simplex virus thymidine kinase gene transfer for controlled graft-versus-host disease and graft-versus-leukemia: clinical follow-up and improved new vectors. 979 8

We examined the incidence of herpes varicella-zoster virus (VZV) infection in 151 patients undergoing allogeneic BMT between August 1990 and September 1997 and who survived at least 3 months. Median follow-up was 17 (range 3.3-80.7) months. Herpes simplex virus antibody positive (HSV+) patients received aciclovir 1200 mg p.o. daily or 750 mg i.v. daily, in divided doses from day 0 to engraftment. Ganciclovir (5 mg/kg i.v. three times per week) was given in CMV+ patients (or if the donor was CMV+) from engraftment to day 84. Ganciclovir was continued or recommenced if a dose of greater than 20 mg of prednisone was used for the treatment of GVHD otherwise aciclovir was recommenced. In HSV+ patients not receiving ganciclovir, aciclovir 600 mg p.o. daily in divided doses was given until at least 6 months after BMT. Thirty-two patients developed VZV infection from 4.1 to 28 months after transplant. The estimated cumulative incidence of VZV was 13% (95% confidence interval 6-19%) at 12 months, 32% (22-42%) at 24 months and 38% (27-50%) at 28 months, with no further cases beyond that time. No patient developed VZV whilst receiving aciclovir or ganciclovir (P < 0.0001). However, there was a rapid onset of VZV following cessation of antiviral therapy (33% (20-46%) at 1 year post cessation). The presence of GVHD and the prior duration of antiviral prophylaxis were significant and independent risk factors for the development of VZV. Age, underlying disease, conditioning therapy or donor type were not. We conclude that 3-6 months of low-dose aciclovir and ganciclovir are effective at delaying the onset of VZV after allogeneic BMT, but may not affect the overall incidence of infection. Prolonged prophylaxis may be warranted in patients at high risk of infection, for example those patients with GVHD.
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PMID:Varicella-zoster infection after allogeneic bone marrow transplantation: incidence, risk factors and prevention with low-dose aciclovir and ganciclovir. 1073 1


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