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)

The main risk factors for cytomegalovirus (CMV) disease in recipients of allogeneic stem cell transplants (SCT) are recipient CMV seropositivity and acute graft-versus-host disease. Currently, two antiviral strategies, prophylactic or preemptive antiviral treatment, are used for prevention of CMV disease. Preemptive treatment is most favorable when short-term (14-day) treatment is applied. Several methods are available for monitoring of CMV reactivation. PCR-based CMV DNA detection assays are the most sensitive methods; however, the clinical benefit of this high sensitivity is unclear. Even more, there is lack of clarity whether PCR tests can better be performed with plasma, whole blood, or peripheral blood leukocyte samples. Recovery of a CMV-specific CD8(+) cytotoxic-T-lymphocyte (CTL) response is necessary for preventing CMV reactivation and disease. Reconstitution of absolute CMV-specific CTL counts to values above 10 x 10(6) to 20 x 10(6) CTLs/liter is associated with protection from CMV disease. In the near future, preemptive therapy might be withheld in patients with CMV reactivation who are shown to have adequate CMV-specific cytotoxic T-cell levels. Antiviral therapy with (val)acyclovir has been studied only as prophylactic treatment for prevention of CMV infection. High-dose oral valacyclovir is more effective than acyclovir when used in addition to preemptive treatment of CMV reactivation with ganciclovir or foscarnet. Three antiviral drugs have been tested for preemptive therapy of CMV reactivation and/or treatment of CMV disease. Although intravenous ganciclovir is considered the drug of choice, foscarnet has similar efficacy and less toxicity, especially hematologic toxicity. Cidofovir has not been tested extensively, but so far the results are disappointing. Oral valganciclovir for preemptive treatment of SCT recipients is currently being studied. In addition to antiviral therapy, adoptive immunotherapy with CMV-specific cytotoxic T cells as prophylactic or preemptive therapy is a very elegant strategy; however, generation of these cells is expensive and time-consuming, and therefore the therapy is not available at every transplantation center. Magnetic selection of CMV-specific CD8(+) T cells from peripheral blood by using HLA class I-peptide tetramers may be very promising, making this strategy more accessible.
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PMID:Prevention of cytomegalovirus disease in recipients of allogeneic stem cell transplants. 1455 91

Invasive adenovirus (AdV) disease is fatal in >50% of allogeneic hematopoietic stem cell transplant (SCT) recipients. Treatment with cidofovir may improve outcomes based on in vitro susceptibility data and case reports. Six consecutive cases of invasive AdV disease treated with cidofovir were reviewed among 84 allogeneic adult SCT recipients (incidence, 7.1%). Cidofovir was administered intravenously at 5 mg/kg per dose (1-7 doses). All patients received intravenous immune globulin. Blood AdV DNA levels (viral loads, VLs) were monitored with a real-time quantitative polymerase chain reaction assay. Published reports of cidofovir treatment of AdV disease in SCT recipients were critically reviewed. The primary manifestations of AdV disease were hepatitis (n = 3), colitis (n = 2), and nephritis (n = 1). All patients had detectable AdV VLs, with peak values from 5 x 10(5) to 2 x 10(8) copies/mL. All patients received CD34+ selected grafts (n = 3) and/or had graft-versus-host disease (n = 4) and had CD4 counts <100 cells/mm3. Only 1 of 5 patients (20%) who received >or=2 doses of cidofovir died with active AdV disease. Four patients exhibited improvement within days of treatment with cidofovir as documented by clinical criteria and declines in AdV VLs (without a change in immunosuppression). In contrast, 1 patient treated late after onset of AdV disease died after 1 dose of cidofovir. In our review of 70 published cases treated with >or=2 doses of cidofovir, 13 (19%) died from AdV disease. In conclusion, early treatment of AdV disease with cidofovir inhibits viral replication in vivo and reduces mortality in allogeneic SCT recipients compared with historical data.
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PMID:Treatment of adenovirus disease in stem cell transplant recipients with cidofovir. 1722 55

Human adenovirus (HAdV) infections are increasingly recognized as important pathogens in immunocompromised hosts, especially in patients with severely suppressed T-cell function. The 4th European Conference of Infections in Leukemia (ECIL-4) has developed evidence-based guidelines for diagnosis and management of HAdV infections. The risk for HAdV-associated disease is increased in children, and risk factors for HAdV disease are T-cell depletion, unrelated and cord blood hematopoietic stem cell transplantation, graft-versus-host disease grades III-IV, and lymphopenia. The recommended technique for monitoring of high-risk patients is quantitative polymerase chain reaction. Cidofovir is the most used antiviral therapy, although no controlled study has been performed. HAdV-specific T-cell therapy is in development.
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PMID:European guidelines for diagnosis and treatment of adenovirus infection in leukemia and stem cell transplantation: summary of ECIL-4 (2011). 2314 63

Many drugs are used for unapproved indications in Japan for post hematopoietic stem cell transplant (HCT) complications. To investigate unapproved or off-label drug usage for graft-versus-host disease (GVHD) and virus infections after allogeneic HCT, we analyzed the data of Japanese HCT registry. Between 2006 and 2017, 39,941 adults and children received HCT for a variety of disease and their transplant data were captured in the registry. Among them, 14,687 and 8914 patients receiving treatment for acute and/or chronic GVHD, 24,828 patients with cytomegalovirus (CMV) infection or receiving therapies for CMV, and 4943 who received treatment for other viral infections were included in the analyses of off-label or unapproved drugs. For GVHD, mycophenolate mofetil was the most frequently used off-label drug, followed by beclomethasone, infliximab, and etanercept. For viral infections other than CMV, foscarnet was the most frequently used off-label drug. Cidofovir, which is not approved for use in Japan, was mainly used for adenovirus infection. This study demonstrated that numerous off-label and unapproved drugs have been used as key drugs for GVHD and post-transplant viral infection, and the real world date in the transplant registry may serve as an important asset to regulatory purposes.
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PMID:Use of unapproved or off-label drugs in Japan for the treatment of graft-versus-host disease and post-transplant viral infection. 3287 87