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)

Since its approval in 1983 for immunosuppressive therapy in patients undergoing organ and bone marrow transplants, cyclosporin has had a major impact on organ transplantation. It has significantly improved 1-year and 2-year graft survival rates, and decreased morbidity in kidney, liver, heart, heart-lung and pancreas transplantation. Several studies have supported the efficacy of cyclosporin in preventing graft-versus-host disease in bone marrow transplantation. Cyclosporin is also possibly effective in treating diseases of autoimmune origin and as an antineoplastic agent. The introduction of therapeutic drug monitoring of cyclosporin was extremely useful because of the wide inter- and intraindividual variability in the pharmacokinetics of cyclosporin after oral or intravenous administration. Optimal long term use of cyclosporin requires careful monitoring of the blood (or plasma) concentrations. Sustained and clinically significant drug-drug interactions can occur during long term therapy with cyclosporin. The coadministration of multiple drugs with cyclosporin could result in graft rejection, renal dysfunction or other undesirable effects. Any interaction that leads to modified cyclosporin concentrations is of potential clinical importance. Cyclosporin itself may have significant effects on the pharmacokinetics and/or pharmacodynamics of coadministered drugs, such as digoxin, HMG-CoA reductase inhibitors and antineoplastic drugs affected by multidrug resistance. Many drugs have been shown to affect the pharmacokinetics and/or pharmacodynamics of cyclosporin. Interactions between cyclosporin and danazol, diltiazem, erythromycin, fluconazole, itraconazole, ketoconazole, metoclopramide, nicardipine, verapamil, carbamazepine, phenobarbital (phenobarbitone), phenytoin, rifampicin (rifampin) and cotrimoxazole (trimethoprim/sulfamethoxazole) are well documented in a large number of patients. Other interactions (such as those with aciclovir, estradiol and imipenem) are documented only in isolated case studies.
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PMID:Clinically significant drug interactions with cyclosporin. An update. 906 30

Hematopoietic stem cell transplantation has become an established treatment for some patients with malignant and non-malignant hematologic diseases. More wide-spread use of this treatment modality is limited by its severe side effects. Graft-versus-host disease is a major cause of morbidity and mortality following allogeneic stem transplantation. Recent data from experimental research in murine models of GVHD and early stage clinical studies demonstrate the potential of statins in the prevention and treatment of acute and chronic GVHD. Statins are lipid lowering drugs, which reduce cholesterol production by inhibiting HMG-CoA reductase, the rate limiting enzyme of the mevalonate pathway. They are an already approved drug class with a well known toxicity profile. Besides lowering of cholesterol levels other pleiotropic effects contribute to the therapeutic activity of statins. Statins have immunomodulatory effects and inhibit a broad range of immune cells that play a role in the pathogenesis of GVHD, including antigen-presenting cells. In addition to preventing GVHD statins possess several other effects that might prove beneficial in the setting of allogeneic transplantation, such as cardiovascular protection and anti-neoplastic activity. Here we review the current knowledge on the use and effects of statins in patients who undergo allogeneic hematopoietic stem cell transplantation with a special focus on prevention and treatment of GVHD.
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PMID:The use of statins in hematopoietic stem cell transplantation. 1950 62

Allogeneic hematopoietic stem cell transplantation is the sole curative modality for a variety of malignant and benign hematological disorders. Despite advances in supportive care and transplant conditioning regimens graft-versus-host disease (GVHD), infectious complications and end organ toxicity remain the leading causes of transplant related mortality (TRM). Development of safe and effective strategies to mitigate these significant complications associated with HSCT, are urgently needed. Statins are lipid lowering drugs, which reduce cholesterol production by inhibiting HMG-CoA reductase, with a well defined toxicity profile. Statins have pleiotropic immunomodulatory effects which are relevant in the context of treating and preventing GVHD. In addition to GVHD statins may possess several other effects that might have clinical benefit in the setting of hematopoietic cell transplantation, such as treatment of bronchiolitis obliterans and antineoplastic activity. Herein we review the emerging role of statins in improving the outcomes of patients undergoing HSCT.
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PMID:The evolving role of statins in hematopoietic stem and progenitor cell transplantation. 2243 66