İmatinib tedavisinin kronik miyeloid lösemi hastalarında erektil fonksiyonlar üzerine etkisinin değerlendirilmesi
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Date
2012
Authors
Tekinalp, Atakan
Journal Title
Journal ISSN
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Publisher
Uludağ Üniversitesi
Abstract
Kronik miyeloid lösemi (KML), 9. ve 22. kromozomlar arasındaki translokasyon sonucu oluşan, philadelphia kromozomu olarak adlandırılan BCR/ABL füzyon geni ve bu genin tirozin kinaz aktivitesi yüksek onkoproteinleri ile karakterize, tüm hematolojik kök hücre serilerini tutan miyeloproliferatif bir hastalıktır. Genellikle ileri yaşlarda görülür. KML'de ispatlanmış etiyolojik bir ajan söz konusu değildir.KML'de allojeneik kök hücre nakli de dâhil çeşitli tedavi yöntemleri uygulanmıştır. Tirozin kinaz inhibitörlerinden (TKİ) imatinibin keşfi ve tedaviye girmesi, tedavi yanıtları ve sağ kalım açısından bir dönüm noktası kabul edilebilir.TKİ ile hücre içi sinyal iletimi, hücre proliferasyonu ve farklılaşması baskılanır. Hayvan çalışmalarında (ratlar, maymunlar ve köpeklerde) imatinibin spermatogenezi etkilediği ancak diyabetik ratlarda diyabete bağlı gelişen erektil disfonksiyonların TKİ tedavisi ile gerileyebileceği gösterilmiştir. TKİ'lerinin teratojenik etkileri olabileceğinden korkulması nedeni ile TKİ kullanan şahısların gebelikten kesin bir şekilde kaçınması gerektiği önerilmektedir.İmatinib kullanımı sırasında gebeliklerin gerçekleştiği ve bunların normal bir şekilde sonlanabildiği de bir gerçektir. İnsanlar üzerinde yapılmış gonadal fonksiyonları inceleyen bir çalışma hali hazırda yoktur. İmatinib tedavisi altındaki erkeklerde erektil fonksiyonları değerlendiren çalışmamız literatürde bir ilki oluşturmaktadır.Çalışmamızda Uludağ Üniversitesi Tıp Fakültesi İç Hastalıkları Anabilim Dalı Hematoloji Bilim Dalı'nda takip ve tedavi altındaki erkek KML hastalar incelendi. KML dışında bilinen bir sistemik hastalık öyküsü olmayan, TKİ dışında farmakolojik tedavi almayan 31 hasta tespit edildi. Bunlardan 24'ü imatinib, 6'sı nilotinib ve 1'i de dasatinib tedavisi almaktaydı. Bu hastaların erektil fonksiyonları, Uluslararası Erektil Fonksiyon Değerlendirme İndeksi (IIEF-5) ile değerlendirildi. Tüm hastaların 12'sinde (%38,7) erektil disfonksiyon (ED) saptanmadı. İmatinib kullanan hasta grubuna bakıldığında 10 hastada (%41,5) ED saptanmazken, 11 hastada (%45,8) hafif, 3 hastada (%12,5) orta şiddette ED bulundu. Bu olgular yaşlarına göre değerlendirildiğinde ED oranı normal sınırlar içinde saptandı. ED ile imatinib kullanım dozu ve tedavi süresi arasındaki ilişki değerlendirildiğinde istatistikî yönden anlamlı bulunmadı (sırasıyla; p=0,255 ve p=0,243). Sonuç olarak; olgu sayısı sınırlı olmakla birlikte bu çalışmada TKİ kullanımının ED oluşturmadığı belirlendi. Hormonal özellikleri de içeren ve daha geniş olgu sayılı çalışmalara ihtiyaç olduğu kanısına varıldı.
Chronic myeloid leukemia (CML) is a myeloproliferative disease that keeps all the haematological stem cell series and characterized by the Philadelphia (Ph) chromosome caused by translocation between 9. and 22. chromosomes so-called BCR/ABL fusion gene and high tyrosine kinase activited oncoproteins of the fusion gene. Usually seen in older age. There is no provenly etiologic agent in CML.Various treatment methods that also included allogeneic stem cell transplantion have been applied in CML. The discovery of tyrosine kinase inhibitör (TKI) imatinib can be considered a turning point in terms of treatment reponses and survival.Intracellular signal transduction, cellular proliferation and differentiation is supressed by TKI. In animal studies (Rats, monkeys and dogs), It has showed that imatinib impairs the spermatogenesis however erectile disfunction caused diabet can degrade by TKI treatment in diabetic rats. Because of the fear of teratogenic effects may be ıts recommended that patient who treated with tyrosin kinases inhibitör is currently avoid to pregnancy.Its also true that pregnancies occurred while receiving imatinib and could result eventful. There is no clinical trials that investigated gonadal functions in human. Our study which was evaluatied of erectile disfunction (ED) in men taking imatinib is a compose such as firstly in literature.In the study, male patients with CML who were treated and applied to outpatient clinic of Uludag University Medical Faculty Internal Medicine Department Hematology Division investigated. Thirty-one patients identified who has no a know history of systemic disease without CML and not used any pharmacological agent out of TKI. Twenty-four of the patients were received imatinib, six of the patients were received nilotinib and one of the patient was receive dasatinib. Erectile functions were evaluated using the International Index of Erectile Function (IIEF-5). Twelve of the all patients (%38,7) were not determined ED. In the imatinib group, 11 of patients (%45,8) had mild severity, 3 of patients (%12,5) had moderate severity while 10 of patients (%41,5) were no determined ED. Rate of ED were determined within normal limites when the cases assesed according to age. Evaluation of the relationship between dosage and during treatment of imatinib with ED were no signicifiantly difference (respectively; p=0,255 and p=0,243). As a result; in this study, it determined that use of TKI do not occur ED although limited number of cases. It was concluded that studies which includes also hormonal features and more number of cases is needed.
Chronic myeloid leukemia (CML) is a myeloproliferative disease that keeps all the haematological stem cell series and characterized by the Philadelphia (Ph) chromosome caused by translocation between 9. and 22. chromosomes so-called BCR/ABL fusion gene and high tyrosine kinase activited oncoproteins of the fusion gene. Usually seen in older age. There is no provenly etiologic agent in CML.Various treatment methods that also included allogeneic stem cell transplantion have been applied in CML. The discovery of tyrosine kinase inhibitör (TKI) imatinib can be considered a turning point in terms of treatment reponses and survival.Intracellular signal transduction, cellular proliferation and differentiation is supressed by TKI. In animal studies (Rats, monkeys and dogs), It has showed that imatinib impairs the spermatogenesis however erectile disfunction caused diabet can degrade by TKI treatment in diabetic rats. Because of the fear of teratogenic effects may be ıts recommended that patient who treated with tyrosin kinases inhibitör is currently avoid to pregnancy.Its also true that pregnancies occurred while receiving imatinib and could result eventful. There is no clinical trials that investigated gonadal functions in human. Our study which was evaluatied of erectile disfunction (ED) in men taking imatinib is a compose such as firstly in literature.In the study, male patients with CML who were treated and applied to outpatient clinic of Uludag University Medical Faculty Internal Medicine Department Hematology Division investigated. Thirty-one patients identified who has no a know history of systemic disease without CML and not used any pharmacological agent out of TKI. Twenty-four of the patients were received imatinib, six of the patients were received nilotinib and one of the patient was receive dasatinib. Erectile functions were evaluated using the International Index of Erectile Function (IIEF-5). Twelve of the all patients (%38,7) were not determined ED. In the imatinib group, 11 of patients (%45,8) had mild severity, 3 of patients (%12,5) had moderate severity while 10 of patients (%41,5) were no determined ED. Rate of ED were determined within normal limites when the cases assesed according to age. Evaluation of the relationship between dosage and during treatment of imatinib with ED were no signicifiantly difference (respectively; p=0,255 and p=0,243). As a result; in this study, it determined that use of TKI do not occur ED although limited number of cases. It was concluded that studies which includes also hormonal features and more number of cases is needed.
Description
Keywords
Kronik miyeloid lösemi (KML), İmatinib, Erektil disfonksiyon, Chronic myeloid leukemia (CML), Imatinib, Erectile dysfunction
Citation
Tekinalp, A. (2012). İmatinib tedavisinin kronik miyeloid lösemi hastalarında erektil fonksiyonlar üzerine etkisinin değerlendirilmesi. Yayınlanmamış uzmanlık tezi. Uludağ Üniversitesi Tıp Fakültesi.