Başkent Üniversitesi Yayınları
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Item Novel Treatment with Rituximab of Oropharyngeal Posttransplant Lymphoproliferative Disorder after Heart Transplantation(Başkent Üniversitesi, 2005-12) Kaczmarek, Ingo; Beiras-Fernandez, Andres; Sadoni, Sebastian; Bengel, Dominik; Deutsch, Marcus-Andre; Meiser, Bruno; Reichart, BrunoPosttransplant lymphoproliferative disorders are severe complications that arise after solid organ transplantation, which are often related to Epstein-Barr virus. Reports are anecdotal, and a standardized therapy does not exist. We report a case of a 36-year-old man who developed posttransplant lymphoproliferative disorder of the oropharynx 1 year after receiving a heart transplant. A short review of the literature is presented, after which a new therapeutic approach that combines antiviral therapy, monoclonal antibodies, and a sirolimus-based maintenance immunosuppression regimen with reduced target trough levels of tacrolimus is introduced. The patient achieved complete remission and was free from recurrence 18 months after the therapy was initiated.Item Complete Regression of Visceral Kaposi’s Sarcoma after Conversion to Sirolimus(Başkent Üniversitesi, 2005-12) Mohsin, N.; Budruddin, M.; Pakkyara, A.; Darweesh, A.; Nayyer, M.; Amitabh, J.; Daar, A. S.The prevalence of Kaposi’s sarcoma (KS) is much greater in organ transplant recipients than it is in the general population. Its etiology appears to be related to geographic, genetic, and viral factors. Treatment of transplant-related KS has, until now, consisted mainly of reduction of, or withholding of, immunosuppression, often with deleterious effects on both graft and patient survival. In recent years, the immunosuppressive drug, sirolimus, has been demonstrated as possessing anti-neoplastic properties in both in vitro and animal models. In view of these properties and some preliminary clinical experience, we postulated that sirolimus would be beneficial in our patients who developed transplant-related KS. Here, we report the first case of a patient with both cutaneous and visceral KS who was successfully treated in the Middle East by conversion from a cyclosporine-based to a sirolimus-based immunosuppression regimen. The KS regressed completely within a few months after the conversion. The chronologic events and the extensive documentation, which included repeat computed tomography scans, are very suggestive of a selective anti-neoplastic effect of sirolimus.Item Mycophenolic Acid Plasma Trough Level: Correlation with Clinical Outcome(Başkent Üniversitesi, 2005-12) Barbari, A.; Stephan, A.; Masri, M A.; Kamel, G.; Karam, A.; Mourad, N.; Kilani, H.; El-Ghoul, B.Objectives: Assess the relationship between clinical diagnosis, state of immunosuppression, mycophenolic acid (MPA) plasma trough levels (MPACmin), and mycophenolate mofetil (MMF) dosage in renal transplant recipients. Materials and Methods: MPACmin were determined in 30 kidney transplant patients, of whom 7 exhibited biopsy-proven acute rejection. The remaining 23 had normal graft function. Graft outcome, defined by clinical diagnosis and serum creatinine level, was compared according to MPACmin, MMF dosage, and total lymphocyte count (LC). Results: Patients with acute rejection had similar MPACmin (2.4 ± 1.7 µg/mL), MMF dosages (1.7 ± 0.5 g), and LCs (0.001165 ± 0.0040 x 109/L) when compared with normal patients (2.2 ± 0.7 µg/mL, 1.7 ± 0.4 g and 0.001160 ± 0.00527 x 109/L) respectively. Rejection rates were comparable irrespective of MPACmin ranges and higher in those receiving the 1-g dose (30%) when compared with those receiving 1.5-g and 2-g doses (12.5% and 11.7%). No relationship was observed between MPACmin and MMF doses, and neither parameter correlated with LC. Conclusions: These results suggest that MPACmin is a poor correlate of clinical outcome and state of immunosuppression. Although the usually recommended dosage of MMF (2 g) may be associated with acute rejection, low-dose MMF (1 g) seems to constitute a higher risk.Item Sirolimus: A Current Perspective(Başkent Üniversitesi, 2003-06) Yakupoğlu, K. Yarkin; D. Kahan, BarrySirolimus, a macrocyclic lactone that displays a novel mechanism of immunosuppressive action, is a critical-dose drug requiring therapeutic drug monitoring for optimal outcomes. The compound was documented in two multicenter, blinded clinical trials to reduce the incidence of acute rejection episodes when used in combination with cyclosporine and steroids vs. azathioprine or placebo comparators. Furthermore, studies utilizing cyclosporine withdrawal documented a long-term benefit on renal function of chronic sirolimus therapy, albeit with a modestly enhanced incidence of acute rejection episodes. Although this application may be useful in selected cases, we believe that minimal initial cyclosporine exposures de novo mitigate the need for eventual withdrawal for chronic nephropathy, while preserving the immunosuppressive synergy during the maintenance phase. Recipients treated de novo with a sirolimuscyclosporine combination tolerate steroid withdrawal at 1 month after living-donor or at 3 to 6 months after cadaveric kidney transplantation with only a 5% risk of acute rejection episodes and 6% incidence of chronic reactions within 3 years. However, sirolimus exacerbates the hypertriglyceridemic and hypercholesterolemic proclivities of transplant recipients, as well as exerts myelosuppressive effects, which are augmented by concomitant therapy with azathioprine or, particularly, with mycophenolate mofetil. Due to its apparent lack of nephrotoxicity, sirolimus has been employed for induction therapy in a calcineurin antag-onist-free regimen in combination with either basiliximab or rabbit antilymphocyte sera for weak or strong immune responders, respectively, followed by introduction of a calcineurin antagonist upon resolution of the ischemia-reperfusion injury. Therefore, sirolimus proffers a potent and unique platform for new immunosuppressive strategies in organ transplantation.Item Organ Transplantasyonu ve Nörolojik Komplikasyonlar(Başkent Üniversitesi, 2006-09) G. Çileker,; S. Benli,; M. Kılınç,; T. ZileliOrgan transplantasyonu son yıllarda gelişmekte olan bir alan olup, immünsüpresan tedavilerin giderek gelişmesiyle başarısı daha da artmaktadır. Bununla birlikte transplant alıcıları sinir sistemini de ilgilendiren çok sayıda komplikasyonla karşılaşmaktadır. Nörolojik komplikasyonlar bütün organ transplantasyonlarında ortak olarak görülen komplikasyonlar ve belli bir organ transplantasyonuna özgü nörolojik komplikasyonlar olmak üzere ikiye ayrılabilir. Nöbetler, santral sinir sistemi enfeksiyonları, inme, ensefalopati ve kullanılan immünsüpresanlara bağlı yan etkiler daha sık görülürken, diğer ilaçların yan etkileri, maligniteler, hareket bozuklukları, nöromusküler ve nörooftalmik komplikasyonlar daha az sıklıkta görülmektedir. Komplikasyonlar ortaya çıktığında her vakanın ayrıntılı sistemik ve nörolojik değerlendirilmeden geçirilmesi esastır. Fırsatçı enfeksiyonlar yönünden dikkatli değerlendirme yapılmalı, kullanılan immünsüpresan ilaçların seviyelerinin değerlendirilmesi ve normal ilaç seviyelerinde de nörotoksisite ihtimali olabileceği göz önünde bulundurulmalıdır. Nörolojik komplikasyonların erken tanısı, tedavi edilebilir ve geri dönüşümlü nedenlerin belirlenmesi, transplantasyonun mortalite ve morbiditesini azaltmaktadır. Neurologic Complications After Organ Transplantation In recent years, there has been an exponential increase in successful organ transplantation that is in part due to recent advances in immunosuppressive regimens. However, some transplant patients continue to experience severe complications, especially those involving the central nervous system (CNS). The neurologic complications of organ transplantation are frequently associated with all types of allografts and can also be specific to a particular type of organ transplantation. Seizures, CNS infection, stroke, encephalopathy, and adverse effects caused by treatment with immunosuppressive drugs are the most common complications. Malignancy, movement disorders, neuroophthalmic and neuromuscular complications, and adverse effects caused by other types of drugs occur less frequently. When such complications do appear, the patient must undergo thorough systemic and neurologic examinations and an equally thorough evaluation for the presence of opportunistic infections. Neurotoxicity caused by treatment with immunosuppressive agents is also a frequent cause of neurologic complications and may experienced with normal serum drug levels. The early diagnosis of neurologic complications and the identification of their reversible and treatable causes can significantly decrease morbidity and mortality rates in patients who undergo organ transplantation.Item Renal Transplantasyon Sonras› Osteoporoz: Güncel Yaklafl›mlar(Başkent Üniversitesi, 2003-05) M. E. Ertörer; N. GüvenerOrgan nakli 20. yüzyılın ikinci yarısından beri son dönem böbrek yetmezliğinin en popüler tedavi yöntemidir. Günümüzde güçlü immünsupresif ajanların kullanıma girmesiyle nakil organ ömrü oldukça uzamıştır, fakat karşılığında bu ajanların transplantasyon sonrası dönemde neden olduğu osteoporoz ciddi bir klinik problem olarak ortaya çıkmıştır. Bu derlemede immünsupresif ajanlar tarafından oluşturulan renal transplantasyon sonrası osteoporozun fizyopatolojisi, klinik önemi ve korunma yöntemleri tartışılacaktır. Osteoporosis After Renal Transplantation: Popular Approaches Renal transplantation has been the most popular treatment modality for end-stage renal failure since the middle of the 20th Century. The introduction of potent immunosuppressive agents has extended graft survival to decades; however, long-term use of these agents can lead to serious metabolic problems, such as post-transplantation osteoporosis. This review focuses on the pathophysiological mechanisms of post-transplantation osteoporosis due to immunosuppressive agents, and also discusses clinical impacts and recommendations for prevention.