Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinase activating genes 1/2 (RAG1/2) deficiency, critical to initiate gene rearrangement encoding lymphocyte receptors, causes T-B- severe combined immunodeficiency (SCID) and Omenn syndrome (OS), characterised by erythroderma, hepatosplenomegaly, lymphadenopathy, activated, clonal T cell expansions with restricted TCRVbeta family usage, and opportunistic infection. Many features of OS resemble graft-versus-host disease (GvHD). Frequency of GvHD-associated cytokine gene polymorphisms (CGPs) with OS was investigated to explain phenotypic differences between T-B- SCID and OS. Allele frequencies of IFNgamma T874A, IFNgamma-R1, TNFalphad microsatellites, IL-10 promoter region C592A and A1082G, IL-4 C-590T, IL-6 G-174C, IL-4R Q+576R, IFNgamma-R1 T-56C, TNFalphaRII 196 M/R single-nucleotide polymorphisms and IL-1Ra intron 1 VNTR were examined in 33 OS and 23 SCID patients. No significant differences in allele frequencies were found between the groups, and no trends identified. The mechanisms determining the OS or T-B-NK+ SCID phenotype remain to be determined.
 ...
PMID:GvHD-associated cytokine polymorphisms do not associate with Omenn syndrome rather than T-B- SCID in patients with defects in RAG genes. 1757 55

Daclizumab has been shown to have activity in acute GVHD, but appears to be associated with an increased risk of infection. To investigate further the long-term effects of daclizumab, we performed a retrospective review of 57 patients who underwent an allogeneic hematopoietic stem cell transplant from January 1993 through June 2000 and were treated with daclizumab for steroid-refractory acute GVHD. The median number of daclizumab doses given was 5 (range 1-22). GVHD was assessed at baseline, days 15, 29 and 43. By day 43, 54% patients had an improvement in their overall GVHD score, including 76% patients aged < or =18. Opportunistic infections developed in 95% patients. Forty-three patients (75%) died following treatment with daclizumab. The causes of death included active GVHD and infection (79%), active GVHD (5%), chronic GVHD (2%) and relapse (14%). Patients with grade 3-4 GVHD had a significantly shorter median survival than patients with grade 1-2 GVHD (2.0 vs 5.1 months, P=0.001). Daclizumab has no infusion-related toxicity, is active in steroid-refractory GVHD, especially among pediatric patients, but is associated with significant morbidity and mortality due to infectious complications. Careful patient selection and aggressive prophylaxis against viral and fungal infections are recommended.
 ...
PMID:Long-term follow-up of patients treated with daclizumab for steroid-refractory acute graft-vs-host disease. 1761 22

Serious infections are a major obstacle limiting the usefulness of unrelated donor marrow transplantation. Graft-versus-host disease (GVHD) and its therapy are associated with a high risk of opportunistic infection. In this study, patients were randomized to receive 1 of 2 GVHD prophylaxis strategies, marrow T cell depletion, and cyclosporine (TCD) or methotrexate/cyclosporine (M/C) after transplantation. The patients underwent transplantation between March 1995 and October 2000 as part of a multicenter randomized trial. As a secondary analysis, we analyzed infections in this study cohort. Among the 404 patients who underwent transplantation, a total of 1598 infections were reported. The rates of serious and fatal infections did not differ between the TCD and M/C groups. Bacterial infections accounted for 1/3 of serious infections in each treatment arm. A significantly higher incidence of severe cytomegalovirus (CMV) and life-threatening or fatal aspergillus infections was observed in the patients receiving TCD (CMV, 28% vs 17% [P = .02]; aspergillosis, 16% vs 7% [P < .01]). The only independent risk factor for serious infection was the development of grade III-IV acute GVHD (aGVHD; hazard ratio = 1.41; 95% confidence interval = 1.03-1.91). Strategies to speed immune recovery, even in the absence of GVHD, are needed to overcome the risk of infection after unrelated donor transplantation.
 ...
PMID:Higher risk of cytomegalovirus and aspergillus infections in recipients of T cell-depleted unrelated bone marrow: analysis of infectious complications in patients treated with T cell depletion versus immunosuppressive therapy to prevent graft-versus-host disease. 1802 79

We report the results of a retrospective analysis in 27 pediatric patients who received low-dose MTX as the second-line treatment for steroid-refractory or -dependent acute and chronic GVHD. Between July 2000 and May 2006, 10 patients with aGVHD and 17 with cGVHD were treated with MTX at a dose of 3-10 mg/m(2) weekly. Seven of ten patients (70%) with aGVHD responded well to MTX, thus resulting in the achievement of either a complete response (CR) or a partial response (PR). The dose of prednisone could be reduced to equal to or lower than 1 mg/kg in the responding patients at the end of MTX therapy. The median number of MTX administrations was five (range, 1-7). Ten (58.8%) of seventeen patients with cGVHD achieved CR or PR. The dose of prednisone could be reduced to lower than 0.4 mg/kg in 16 of 17 patients and seven patients could discontinue prednisone. The median duration of MTX administration was 18 months (range, 1-68). The toxicities of grade III to IV occurred in only six patients presenting cytopenias or elevated levels of serum transaminases. Low-dose MTX was tolerable and effective for the steroid-refractory or -dependent GVHD in reducing the dose of steroid without increasing the risk of opportunistic infection.
 ...
PMID:Low-dose MTX for the treatment of acute and chronic graft-versus-host disease in children. 1802 50

Although allogeneic hematopoietic progenitor cell transplant (HPCT) is curative therapy for many disorders, it is associated with significant morbidity and mortality, which can be related to graft-versus-host disease (GVHD) and the immunosuppressive measures required for its prevention and/or treatment. Whether the immunosuppression is pharmacologic or secondary to graft manipulation, the graft recipient is left at increased risk of the threatening opportunistic infection. Refractory viral diseases in the immunocompromised host have been treated by infusion of virus-specific lymphotyces and by unmanipulated donor lymphocyte infusion (DLI) therapy. L-leucyl-L-leucine methyl ester (LLME) is a compound that induces programmed cell death of natural killer (NK) cells, monocytes, granulocytes, most CD8(+) T cells, and a small fraction of CD4(+) T cells. We have undertaken a study of the use of LLME-treated DLI following T cell-depleted allogeneic HPCT, specifically to aid with immune reconstitution. In this ongoing clinical trial, we have demonstrated the rapid emergence of virus-specific responses following LLME DLI with minimal associated GVHD. This paper examines the pace of immune recovery and the rapid development of antiviral responses in 6 patients who developed viral infections during the time period immediately preceding or coincident with the administration of the LLME DLI.
 ...
PMID:Antiviral responses following L-leucyl-L-leucine methyl esther (LLME)-treated lymphocyte infusions: graft-versus-infection without graft-versus-host disease. 1974 72

Opportunistic infection remains the principal cause of mortality in allogeneic stem cell transplant recipients with active extensive chronic graft-versus-host disease. Human cytomegalovirus (HCMV) represents an important cause of disease in this setting and the toxicity of protracted and recurrent antiviral treatment together with eventual drug resistance represents a significant limitation to therapy. Although the expansion and adoptive transfer of HCMV-specific T cells from the healthy original donor can be an effective strategy to control viral replication, this is not possible when donors are seronegative or are subsequently inaccessible. Here we demonstrate for the first time, the successful expansion of HCMV-specific T cells from a seropositive transplant recipient of a seronegative graft with active HCMV disease and the long-term reconstitution of protective antiviral immunity following their adoptive transfer back into the patient.
 ...
PMID:Successful immunotherapy of HCMV disease using virus-specific T cells expanded from an allogeneic stem cell transplant recipient. 1991 60

A single institution case series of adenovirus infections after allogeneic hematopoietic stem cell transplantation is presented to highlight the consideration for adenovirus infections as an etiology in patients with rapid hepatic or other sudden organ deterioration in the setting of apparent GVHD stabilization. The series also highlights that survival is limited with these infections often due in part to concomitant opportunistic infections. In addition, the pathophysiological events, such as GVHD and hepatic dysfunction, may complicate the clinical picture and delay therapy of an opportunistic infection. This is particularly true for adenoviral infections as they also have a distinct clinical picture in immunocompromised patients when compared to immune competent patients. Adenovirus infections also have the additional challenge that its treatment, cidofovir, has associated toxicities that can delay its administration. Recent developments has yielded an assay that can be used in the early detection and for serial determinations of adenovirus in patients with advanced GVHD, as well as a new therapeutic agent currently undergoing clinical trials.
 ...
PMID:Life-threatening adenovirus infections in the setting of the immunocompromised allogeneic stem cell transplant patients. 2067 48

Although allogeneic hematopoietic stem cell transplantation (HSCT) is an established treatment for Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL), the prognosis of patients who relapse after allogeneic HSCT has been extremely poor. Dasatinib, a second-generation tyrosine kinase inhibitor, is a promising agent for the treatment of Ph-ALL. We report on a Ph-ALL patient who relapsed early after the first allogeneic HSCT, but achieved complete molecular remission with dasatinib alone. She remains in molecular remission 12 months after the second allogeneic HSCT. Dasatinib was generally well tolerated, but she developed myalgia, nausea and positive cytomegalovirus antigenemia. In addition, sudden-onset bloody diarrhea was observed 10 days after the second HSCT, which was possibly associated with the use of dasatinib in addition to the effect of the conditioning regimen and graft-versus-host disease. In conclusion, dasatinib is an effective agent for Ph-ALL with a poor prognosis, but may be associated with specific adverse events including opportunistic infection and gastrointestinal bleeding.
 ...
PMID:Dasatinib followed by second allogeneic hematopoietic stem cell transplantation for relapse of Philadelphia chromosome-positive acute lymphoblastic leukemia after the first transplantation. 2082 99

Invasive aspergillosis (IA) is a live-threatening opportunistic infection that is best described in haematological patients with prolonged neutropenia or graft-versus-host disease. Data on IA in non-neutropenic patients are limited. The aim of this study was to establish the incidence, disease manifestations and outcome of IA in non-neutropenic patients diagnosed in five Swiss university hospitals during a 2-year period. Case identification was based on a comprehensive screening of hospital records. All cases of proven and probable IA were retrospectively analysed. Sixty-seven patients were analysed (median age 60 years; 76% male). Sixty-three per cent of cases were invasive pulmonary aspergillosis (IPA), and 17% of these were disseminated aspergillosis. The incidence of IPA was 1.2/10 000 admissions. Six of ten cases of extrapulmonary IA affected the brain. There were six cases of invasive rhinosinusitis, six cases of chronic pulmonary aspergillosis, and cases three of subacute pulmonary aspergillosis. The most frequent underlying condition of IA was corticosteroid treatment (57%), followed by chronic lung disease (48%), and intensive-care unit stays (43%). In 38% of patients with IPA, the diagnosis was established at autopsy. Old age was the only risk factor for post-mortem diagnosis, whereas previous solid organ transplantation and chronic lung disease were associated with lower odds of post-mortem diagnosis. The mortality rate was 57%.
 ...
PMID:Survey of aspergillosis in non-neutropenic patients in Swiss teaching hospitals. 2095 Mar 31

Our team conducted an original procedure of hematopoietic transplantation of umbilical cord blood (UCB) from an unrelated donor. The procedure consists of co-infusing hematopoietic stem cells selected from the blood of a third-party donor; it is conceived as a tool to shorten the engraftment period without preventing the engraftment of the UCB, even when using units with relatively low cell content and a low HLA compatibility. Between 1999 and 2008 we performed 64 transplantations in 60 adult patients (35 men and 25 women) with a median age of 34 years (range: 76-60) and a median weight of 70 kg (range: 43-95), all of whom were diagnosed with a high risk hematologic neoplasm (leukemia in most cases). Fludarabine, cyclophosphamide, ATG, and whole body irradiation or busulfan were used as conditioners. UCB was infused at medians of 2.4 x 107 CNT/kg (range: 1.14-4.30 x 107), 0.11 x 106 CD34+/kg (range: 0.035-0.37 x 106). Then, hematopoietic stem cells selected from the third-party donor were infused (2.43 x 106/kg [range: 1.05-3.34 x 106], with 0.3 x 104 CD3+/kg [range: 0.05-1.56 x 104]). Granulocyte engraftment occurred (ANC > 0.5 x 109/L) at a median of 10 days (range: 9-34 days), and the granulocyte engraftment of the UCB occurred in 21 days (range: 13-57 days). Complete UCB chimerism was observed in 37 days (range: 11-186 days) (previously double complete chimerism, presence of third-party donor and of cord) and platelet engraftment > 20 x 109/L in 33 days (range: 13 98 days) and > 50 x 109/L in 58 days (range: 14-106 days). Overall 3-year survival reached 51%, and 5 10 year-survival was 47% (plateau). Disease-free survival was 48% at three years, and 45% at 5 to 10 years; the mean follow-up of survivors was 48 months (range: 13-123 months). (Kaplan-Meier). In conclusion, early granulocyte recovery occurred thanks to a foster engraftment of hematopoietic stem from the third-party donor, which are not HLA-restricted; this is associated with a lower morbidity and mortality from infections secondary to neutropenia. There was also a high rate of engraftment and final full UCB chimerism, even with non-histocompatible UCB units (2/6 HLA mismatches) and with relatively low cell counts. In most cases, a single unit of UCB was sufficient. The incidence of severe GVHD and the percentage of relapses have been low. Opportunistic infections have occurred over a long period of time. This procedures makes allogeneic hematopoietic transplantation accessible to almost all patients.
 ...
PMID:[Umbilical cord blood cell transplantation from an unrelated donor: dual transplantation]. 2138 Dec 88


<< Previous 1 2 3 4 5 6 Next >>