Etkin faktör yerine koyma tedavisi ve deðiþik tedavi programlarýna raðmen günümüzde hemofilinin profilaktik tedavisinde hala çözülmemiþ sorunlar ve karþýlanmamýþ gereksinimler vardýr. Bu nedenle kanama riski ve kanamaya baðlý komplikasyonlar önemini korumaktadýr. Bu baðlamda profilakside kullanýlacak uzatýlmýþ yarý ömürlü rekombinant faktör VIII ve faktör IX ürünleri tedavinin güvenlilik ve etkililiðinden ödün vermeksizin doz sýklýðýnýn azaltýlmasý, hasta uyumunun artmasý ve yaþam kalitesinin düzelmesini saðlayarak optimal tedavi koþullarýnýn oluþmasýna yardýmcý olabilir. Uzatýlmýþ yarý ömürlü faktörler infüzyon sýklýðýný artýrmadan daha yüksek çukur deðerler ulaþýlmasý veya mevcut çukur deðerin daha seyrek infüzyonla idamesi konusunda önemli bir açýlým saðlayabilir. Bu derlemede uzatýlmýþ yarý ömürlü faktör konsantrelerinin geliþtirilmesine neden gerek duyulduðu, hemofili tedavisindeki olasý yerleri, faktör yarý ömrünü uzatmak için kullanýlan teknikler ve mevcut uzatýlmýþ yarý ömürlü faktör konsantrelerinin etkililik, güvenlilik ve endikasyonlarý ile iliþkili kapsamlý bilgi sunulacaktýr. Ayrýca bu ürünlerin yaþam kalitesi ve saðlýk ekonomisi üzerine etkileri, immün tolerans tedavisindeki yerleri, farmakokinetik temelli profilaside kullanýmlarý ile laboratuvar izleminde karþýlaþýlan güçlükler tartýþýlacaktýr.

Despite effective factor replacement and various treatment schedules, there remain several challenges and unmet needs in the prophylactic treatment of hemophilia limiting its adoption and thereby posing an increased risk of spontaneous bleeding. In this regard, extended half-life (EHL) recombinant factor VIII (rFVIII) and factor IX (rFIX) products promise optimal prophylaxis by decreasing the dose frequency, increasing the compliance, and improving the quality of life without compromising safety and efficacy. EHL products might lead to higher trough levels without increasing infusion frequency, or could facilitate the ability to maintain trough levels while reducing infusion frequency. This paper aims to provide a comprehensive review of the rationale for developing EHL coagulation factors and their utility in the management of hemophilia, with special emphasis on optimal techniques for half-life extension and criteria for defining EHL coagulation factors, as well as indications, efficacy, and safety issues of the currently available EHL-rFVIII and EHL-rFIX products. Potential impacts of these factors on quality of life, health economics, and immune tolerance treatment will also be discussed alongside the challenges in pharmacokinetic-driven prophylaxis and difficulties in monitoring the EHL products with laboratory assays.

Abstract | Full Text PDF

Amaç: Çalýþmanýn amacý <5 ve 5-7 yaþ arasý kanser tanýsý alýp tedavi görmüþ hastalarda diþ anomalileri (DA) (mikrodonti, hipodonti, hiperdonti, mine kusuru, kök þekil bozukluðu) sýklýðýný belirlemek ve alýnan tedavi ile iliþkini saptamaktýr.
Gereç ve Yöntem: Kanser tanýsý alýp 7 yaþ öncesi tedavi görmüþ çocuk hastalar olgu kontrol yöntemiyle araþtýrýldý. Kanser tedavisinin üzerinden en az 5-8 yýl geçmiþ, taný yaþý 9 ay ile 7 yýl arasýnda deðiþen, 93 hasta çalýþmaya dahil edildi. Grup A 9 ay-4 yaþ arasýndaki hastalardan, Grup B 5-7 yaþ arasýndaki hastalardan oluþuyordu. Kontrol grubu olarak hastalarýn yaþ aralýðý uygun 72 kardeþi alýndý. Hasta ve kontrol grubunun aðýz içi muayeneleri yapýldý ve panoramik radyografileri alýndý.
Bulgular: Doksan üç hastanýn yaþ ortalamasý 9,54±1,25 (daðýlým 8-13 yýl) ve 48’i (%51,6) erkekti. En sýk rastlanan taný, %65,5 oranýnda hematolojik malignitelerdir. En az bir tane DA, hasta grubunun 78’inde (%83,9) ve kontrol grubunun 7’sinde (%9,7) saptandý. Çalýþma grubundaki hastalarda her çeþit DA görülürken, kontrol grubunda sadece mine kusuru vardý. Grup A’da mikrodonti (p=0,077), hipodonti (p=0,058) oranlarýnýn, Grup B’ye göre daha yüksek olduðu saptandý. Kök þekil bozukluðu kemoterapi ve radyoterapi alan hastalarda sadece kemoterapi alanlara göre daha fazla görüldü (p=0,006).
Sonuç: Bu çalýþmada 7 yaþýndan önce kanser tedavisi gören hastalarýn DA’lar yönünden yüksek riskli grup oluþturduðu saptanmýþtýr. Hastalar 5 yaþýndan önce kanser tedavisi gördüðünde mikrodontia ve hipodontinin sýklýðý daha da artmýþtýr.

Objective: The aim of this study is to determine the frequency of dental anomalies (DAs) (microdontia, hypodontia, hyperdontia, enamel defect, root malformation) in pediatric cancer patients at the ages <5 years and between 5 and 7 years, and understand their relationship with the received therapy.
Materials and Methods: Pediatric patients who were diagnosed with cancer and treated before the age of 7 years were investigated in a case- control design. The study included 93 pediatric patients whose ages at diagnosis were between 9 months and 7 years and whose treatments were completed before 5-8 years. Group A consisted of patients in the age range of 9 months to 4 years and Group B consisted of patients in the age range of 5-7 years. Seventy-two siblings with compatible dental age ranges were included in the control group. For both groups, intraoral examinations were performed and panoramic radiographs were taken.
Results: Among the 93 pediatric patients, the mean age was 9.54±1.25 (range: 8-13 years) and 48 (51.6%) patients were male. The most common diagnosis was hematologic malignancy with a rate of 65.5%. At least one DA was detected in 7 (9.7%) individuals of the control group and in 78 (83.9%) of the patient group. While the patients in the study group had all kinds of DAs, those in the control group had only enamel defects. The rates of microdontia (p=0.077) and hypodontia (p=0.058) were detected to be significantly higher in Group A than in Group B. Root malformation was more common in patients receiving chemotherapy and radiotherapy than in those receiving only chemotherapy (p=0.006).
Conclusion: In this study it was found that the pediatric patients who received cancer treatment before the age of 7 years constituted a high-risk group for DAs. The frequencies of microdontia and hypodontia were increased even more when the patient was treated for cancer before 5 years of age.

Abstract | Full Text PDF

Amaç: Daha önceki çalýþmalarýmýzda Populus × robusta’dan doðal olarak oluþan sitokin orto-topolin ribozidin (oTR) mitokondrial apopitotik yolaklar ve endoplazmik retikulum stres yolaklarý vasýtasýyla önemli bir antikanser potansiyelinin olduðunu göstermiþtik. Bu çalýþmada, oTR’nin AML M2 subtipi özelliðindeki HL-60 hücre serisinde diferansiyasyonu indüklediðini gösterdik.
Gereç ve Yöntem: HL-60 hücrelerinin oTR ile inkübasyonunu takiben hücre üzerideki etkileri hücre canlýlýk testleri, Wright-Giemsa boyamasý, CD11b protein ekspresyon analizi, western blot analizi ve polimeraz zincir reaksiyonu ile araþtýrýldý.
Bulgular: oTR’nin hücre siklusunun S fazýnda duraklattýðýný, myeloid hücre yüzey belirteçlerinden CD11b ekspresyonunun arttýðýný, çekirdek sitoplazma oranýnýn azaldýðýný ve çekirdeðin atnalý þeklinin deðiþtiðini Wright-Giemsa boyasý ile destekleyerek gördük. oTR ile muamele edilmiþ hücrelerde fosforile STAT3 protein düzeyinin azaldýðýný, fosforile STAT1’in ise aktive olduðunu bulduk. Ayrýca fosforile STAT3 ve yukarý yöndeki kinaz olan Janus kinaz 2’nin, hücrelerin oTR ile inkübasyonunda artmýþ zamanla inhibe olduðu görüldü. Ek olarak fosforile SHP-1 düzeyleri artarken fosforile SHP-2 düzeyi azaldý.
Sonuç: Birlikte deðerlendirildiðinde, sonuçlarýmýz oTR ile STAT3 inhibisyonu üzerinden bir diferansiyasyon indükleme mekanizmasýný iþaret etmektedir. Bu nedenle, oTR AML tedavisinde yeni bir diferansiyasyon-indükleyici terapötik olarak yer alabilir.

Objective: We previously demonstrated that ortho-topolin riboside (oTR) as a naturally occurring cytokinin secreted from Populus × robusta has great potential anticancer effects via the mitochondrial apoptotic pathway and endoplasmic reticulum stress pathway. In the present study, we reveal that oTR induced the differentiation of acute myeloid leukemia (AML) HL-60 cells, which represent the M2 subtype of AML.
Materials and Methods: After the incubation of HL-60 cells with oTR, its effect was analyzed with cell viability assay, Wright-Giemsa staining, CD11b protein expression analysis, western blot analysis, and polymerase chain reaction.
Results: We found that oTR arrested the cell cycle at the S phase, upregulated the expression of myeloid surface marker CD11b, reduced the nuclear cytoplasmic ratio, and altered the horseshoe shape of nuclei, as evidenced by Wright-Giemsa staining. Furthermore, we found that the protein level of phosphorylated STAT3 was decreased when cells were treated with oTR, while phosphorylated STAT1 was activated. Moreover, the protein level of phosphorylated STAT3 and its upstream kinase, Janus kinase 2, were also inhibited when cells were treated with oTR after increased time. Additionally, the levels of phosphorylated SHP-1 were increased while phosphorylated SHP-2 was decreased.
Conclusion: Collectively, our data indicate a differentiation-induced mechanism underlying the inhibition of STAT3 signaling upon treatment with oTR. Therefore, oTR may constitute a novel differentiation-induced therapeutic for use in clinical treatment of AML.

Abstract | Full Text PDF

Amaç: Son yýllarda eriþkinlerde akut lenfoblastik löseminin (ALL) tedavi yönetiminde önemli geliþmeler meydana gelmiþtir. Bununla birlikte, özellikle rutin uygulamada tedavi sonuçlarý hala tatmin edici deðildir. Çalýþmanýn amacý, Türkiye’de birden fazla merkezde takip edilen geniþ bir ALL hasta grubunun genel klinik özelliklerini, tedavi özelliklerini ve saðkalým sonuçlarýný deðerlendirmektir.
Gereç ve Yöntem: Ocak 2003 ile Haziran 2017 tarihleri arasýnda on farklý merkezdeki hematoloji kliniðinde taný konulan ve farklý protokollerle tedavi edilen ALL hastalarýnýn verilerinin retrospektif analizi yapýldý. Çalýþmaya yaþlarý 17 ile 76 arasýnda deðiþen toplam 288 hasta dahil edildi. Bu çalýþmada ALL’li hastalar tedavi periyoduna, Philadelphia kromozom pozitifliðine, tedavi protokolü ve allojenik hematopoetik kök hücre nakli (AHKHN) yapýlýp yapýlmamasýna göre sýnýflandýrýldý.
Bulgular: Olgularýn 224’ü B-ALL, 64’ü T-ALL idi. Tüm hastalar için ortanca takip süresi 18,2 ay (daðýlým, 0,03-161 ay) idi. Philadelphia kromozomu (Ph+) pozitifliði 49 (%21,9) hastada saptandý ve 54 hastaya (%18,8) AHKHN yapýldýðý izlendi. Ýndüksiyon kemoterapisinden sonra 219 hasta (%76) tam remisyona girdi, 32 hasta tedaviye refrakter (%11,2) olarak deðerlendirildi, 37 hastada ise (%12,8) mortalite gözlendi. Ortanca genel saðkalým 47,7 ay (%95 güven aralýðý: 36,1-59,2) ve ortanca hastalýksýz saðkalým tüm hastalar için 23,4 ay (%95 güven aralýðý: 6,7-40,0) idi.
Sonuç: Sonuç olarak, çok merkezli çalýþmalar, belirli bir hastalýðýn spesifik klinik özelliklerini tanýmlamak için büyük öneme sahiptir. Bu çalýþmanýn sonuçlarý, Türk ALL hasta profili hakkýnda deðerli bilgiler saðlayan gerçek hayat verilerini yansýttýðý için literatüre önemli bir katký saðlayacaktýr.

Objective: Significant developments occurred in the clinical management of acute lymphoblastic leukemia (ALL) in adults in recent decades. However, treatment results are still not satisfactory, especially in routine practice. The objective of this study was to evaluate the general clinical features, treatment details, and outcomes of a large group of patients followed in multiple centers in Turkey with a diagnosis of ALL.
Materials and Methods: A retrospective analysis of the data of patients with ALL was made, the patients having been diagnosed and treated between January 2003 and June 2017 by different protocols in the hematology clinics of ten different centers. A total of 288 patients, aged between 17 and 76 years old, were included in the study. In this retrospective multicenter analysis of patients with ALL, classification of patients was performed based on treatment period, Philadelphia chromosome positivity, treatment regimen, and administration of allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Results: The majority of cases were B-cell in origin, while 224 patients had B-ALL and 64 of the patients had T-ALL. Median follow-up duration for all patients was 18.2 months (range: 0.03-161 months). Philadelphia chromosome positivity was determined in 49 patients (21.9%), and 54 patients (18.8%) were receiving allo-HSCT. After induction chemotherapy, 219 patients (76.0%) achieved complete remission, 32 patients (11.2%) were evaluated as treatment refractory, and 37 patients (12.8%) were deceased. Median overall survival was 47.7 months (95% confidence interval: 36.1-59.2) and median disease-free survival was 23.4 months (95% confidence interval: 6.7-40.0) for all patients.
Conclusion: Multicenter studies are extremely important for defining the specific clinical features of a particular disease. The results of this study will make a significant contribution to the literature as they reflect real-life data providing valuable information about the Turkish ALL patient profile.

Abstract | Full Text PDF

Amaç: Anjiyotensin II, bazý tümörlerde tip 1 reseptörleri (AGTR1) yoluyla bir büyüme promotörü veya anjiyojenik faktör olarak görev yapar. Bu çalýþmada, multipl myelomda (MM) kemik iliði AGTR1 ekspresyonunu ve bunun anjiyogenez ve prognostik faktörlerin düzenlenmesi ile iliþkisini incelemekteyiz.
Gereç ve Yöntem: Otuz dokuz MM hastasý ve 15 saðlýklý kontrolde, kemik iliði AGTR1 mRNA düzeyleri kantitatif RT-PCR ile analiz edildi. Kemik iliði anjiogenezi, doku vasküler endotel büyüme faktörü (VEGF), CD34 ve faktör VIIIrAg’nýn (fVIIIrAg) immünohistokimyasal ölçümü ile deðerlendirildi.
Bulgular: Hastalar kontrollerle karþýlaþtýrýldýðýnda daha yüksek kemik iliði VEGF, fVIIIrAg, CD34 ve AGTR1 ekspresyon seviyelerine sahipti ve þiddetli yaygýn kemik iliði infiltrasyonu olan hastalar diðer hastalara göre daha yüksek kemik iliði VEGF, fVIIIrAg, CD34 ve AGTR1 mRNA seviyeleri gösterdi.
Sonuç: AGTR1 ekspresyonu, plazma β2-mikroglobulin seviyesi ile korele bulundu ve artan AGTR1 ekspresyonu olan hastalarda kemik iliði CD34 seviyelerinde artýþ görüldü.

Objective: Angiotensin II promotes growth and angiogenesis via type 1 receptors (AGTR1) in certain tumors. In this study, we examine the bone marrow AGTR1 expression in multiple myeloma (MM) and its relationship with the regulation of angiogenesis and prognostic factors.
Materials and Methods: Bone marrow AGTR1 mRNA levels of 39 MM patients and 15 healthy controls were analyzed with quantitative RT-PCR. Immunohistochemical staining of the tissue vascular endothelial growth factor (VEGF), CD34, and factor VIIIrAg (fVIIIrAg) was used to assess bone marrow angiogenesis.
Results: Bone marrow samples of the patients showed increased VEGF, fVIIIrAg, and CD34 staining and higher AGTR1 expression levels when compared to controls. Patients with severe-diffuse bone marrow infiltration showed higher bone marrow VEGF, fVIIIrAg, CD34, and AGTR1 mRNA levels when compared to other patients.
Conclusion: AGTR1 expression was found positively correlated with plasma β2-microglobulin level and patients with increased AGTR1 expression showed increased bone marrow CD34 levels.

Abstract | Full Text PDF

Amaç: Amaç: Steroid dirençli akut graft versus host hastalýðý (sdAGVHH), allojenik kök hücre naklinden sonra en önemli morbidite ve mortalite nedenidir. Mezenkimal kök hücre (MKH) uygulamasý da dahil olmak üzere çeþitli tedavi yöntemleri mevcuttur. Bu çalýþmanýn amacý, sdAGVHH’li çocuklarda yapýlan MKH tedavisi sonuçlarýný deðerlendirmektir.
Gereç ve Yöntem: Merkezimizde sdAGVHH geliþen 22 hasta için Kasým 2014 - Aralýk 2017 tarihleri arasýnda MKH tedavisi uygulandý. Hastalar tedaviye yanýt ve saðkalým yönünden retrospektif olarak deðerlendirildi..
Bulgular: MKH uygulanmasýndan sonra, deneklerin %45,5’inde tam cevap, %13,6’sýnda kýsmi yanýt alýnmýþtýr. Deneklerin %40,9’unda yanýt alýnamamýþtýr. Hastalarýn %45,5’inin hayatta olduðunu ve %54,5’inin öldüðünü ve tedavi sonuçlarýmýzýn literatürle benzer olduðunu bulduk. MKH tedavisine yanýt mortaliteyi etkileyen tek prognostik belirteç olarak bulundu.
Sonuç: MKH uygulamasý, mortalite oraný yüksek bir durum olan sdAGVHH’de diðer tedavi yöntemleriyle birlikte güvenle kullanýlabilecek bir tedavi yöntemidir. Neredeyse hiçbir akut yan etkisi yoktur. Ayrýca literatürde uzun vadeli ciddi bir yan etkisi yoktur. Prospektif randomize çalýþmalar, yüksek kaliteli veri elde etmek için gereklidir

Objective: Objective: Steroid-resistant acute graft-versus-host disease (srAGVHD) is the most important cause of morbidity and mortality after allogeneic stem cell transplantation. There are several treatment methods available, including mesenchymal stem cell (MSC) application. The aim of this study was to evaluate the results of MSC therapy performed in children with srAGVHD.
Materials and Methods: MSC therapy was used in our center between November 2014 and December 2017 for 22 patients who developed srAGVHD. The patients were retrospectively evaluated in terms of treatment response and survival.
Results: After application of MSCs, complete response was obtained in 45.5% of the subjects, partial response was obtained in 13.6%, and no response was obtained in 40.9%. We found that 45.5% of the patients were alive and 54.5% had died and our treatment results were similar to those in the literature. Response to MSC treatment was found to be the only prognostic marker affecting mortality.
Conclusion: MSC application is a treatment method that can be used safely together with other treatment methods in srAGVHD, a condition that has a high mortality rate. There are almost no acute side effects. There are also no serious long-term side effects in the literature. Prospective randomized studies are required to obtain high-quality data.

Abstract | Full Text PDF

Amaç: Çalýþmanýn amacý hastanede dahili hastalýklar nedeniyle yatan hastalarda ardýþýk kompresyon cihazlarýnýn (SCD) venöz tromboemboliyi (VTE) önlemedeki etkinliðinin deðerlendirilmesidir.
Gereç ve Yöntemler: Çalýþmaya Nisan 2015 ile Mart 2016 tarihleri arasýnda eðitim hastanesine yatan eriþkin hastalar alýnmýþtýr. Antikoagülan tedavi alanlar, SCD kullanýlsýn ya da kullanýlmasýn, çalýþma dýþýnda býrakýlmýþtýr. VTE riski, hastanede yatýþ süresi ve diðer komorbiditeler eðilim skoru eþlenmiþ SCD grubu ve tromboproflaksi kullanmayan grup (NONE) için analiz edilmiþtir.
Bulgular: 30,824 hastadan 67 hasta (%0,22) hastanede yatýþ süresi içinde VTE geçirdi, bunlarýn 55 tanesi derin ven trombozu (DVT), 12 tanesi pulmoner emboli (PE) idi. SCD kullanýlan 20,018 hastadan 47’sinde (41 DVT, 6 PE), SCD kullanmayan 10,819 hastanýn 20’sinde (14 DVT, 6 PE) VTE görüldü. Riske göre düzeltilmiþ analiz SCD grubu ve NONE grubu arasýnda VTE insidansýnda anlamlý bir farklýlýk göstermemiþtir (odds oraný 0,99, %95 güven aralýðý 0,57-1,73, p=0,74).
Sonuç: Yatýþ süresince SCD grubunda NONE grubu ile karþýlaþtýrýldýðýnda VTE insidansýnda bir azalma gözlenmemiþtir.

Objective: To evaluate the effectiveness of sequential compression devices (SCDs) for venous thromboembolism (VTE) prevention in medically ill hospitalized patients.
Materials and Methods: Adult patients admitted to a teaching hospital from April 2015 to March 2016 were included. Patients on anticoagulants with or without SCDs were excluded. We analyzed VTE risk, length of hospital stay, and other comorbidities among propensity score-matched patients on SCDs and those without thromboprophylaxis (NONE).
Results: Among 30,824 patients, 67 patients (0.22%) developed VTE during their hospital stays, with deep vein thrombosis (DVT) in 55 cases and pulmonary embolism (PE) in 12. VTE was seen in 47 out of 20,018 patients on SCDs (41 DVT, 6 PE) and 20 out of 10,819 patients without SCDs (14 DVT, 6 PE). Risk-adjusted analysis showed no significant difference in VTE incidence in the SCD group compared to NONE (odds ratio 0.99, 95% confidence interval 0.57-1.73, p=0.74).
Conclusion: Compared to the NONE group, SCDs are not associated with decreased VTE incidence during hospital stay.

Abstract | Full Text PDF

Abstract | Full Text PDF

Abstract | Full Text PDF

Abstract | Full Text PDF

Abstract | Full Text PDF

Abstract | Full Text PDF

Abstract | Full Text PDF

Abstract | Full Text PDF

Abstract | Full Text PDF

Abstract | Full Text PDF

Abstract | Full Text PDF

Abstract | Full Text PDF

Abstract | Full Text PDF