Güldane Cengiz Seval

Treatment of Acute Myeloid Leukemia in Adolescent and Young Adult Patients.

The objectives of this review were to discuss standard and investigational treatment strategies for adolescent and young adult with acute myeloid leukemia, excluding acute promyelocytic leukemia. Acute myeloid leukemia (AML) in adolescent and young adult patients (AYAs) may need a different type of therapy than those currently used in children and older patients. As soon as AML is diagnosed, AYA patient should be offered to participate in well-designed clinical trials. The standard treatment approach for AYAs with AML is remission induction chemotherapy with an anthracycline/cytarabine combination, followed by either consolidation chemotherapy or stem cell transplantation, depending on the ability of the patient to tolerate intensive treatment and cytogenetic features. Presently, continuing progress of novel drugs targeting specific pathways in acute leukemia may bring AML treatment into a new era.

Lymphoproliferative disorders in individuals with chronic hepatitis b and C in the Turkish population

The aims of this cohort study were to evaluate the association of malignant lymphoproliferative disorders in patients with chronic viral hepatitis and to compare the results with those in individuals with non‐alcoholic fatty liver disease. A total of 3,873 patients with chronic liver disease who were seen consecutively in the Liver Disease Outpatient Clinic between January 2001 and July 2007 were assessed retrospectively. The frequency of malignant lymphoproliferative disorders including non‐Hodgkins lymphoma, Hodgkins lymphoma, and chronic lymphocytic leukemia in these patients was investigated. Of the total, 1,999 patients had chronic hepatitis B infection (male/female: 1,226/773, mean age: 45.1 ± 13.2 years), 978 had chronic hepatitis C infection (male/female: 437/541, mean age: 53.8 ± 13.7 years), and the remaining 896 had non‐alcoholic fatty liver disease (male/female: 450/446, mean age: 50.8 ± 11.2 years). A malignant lymphoproliferative disorder was identified in 13 patients (male/female: 9/4, mean age: 52.8 ± 16.8 years) with chronic viral hepatitis, while no case of malignant lymphoproliferative disorder was identified in individuals with non‐alcoholic fatty liver disease (P = 0.048). Among the patients with malignant lymphoproliferative disorders, seven had chronic hepatitis B infection and six had chronic hepatitis C infection; 11 had non‐Hodgkins lymphoma and two had chronic lymphocytic leukemia. All non‐Hodgkins lymphoma cases were B‐cell lymphoma. Based on the data obtained in this investigation, the association with malignant lymphoproliferative disorders in chronic viral hepatitis seems to be high as compared to that occurring in individuals with non‐alcoholic fatty liver disease. J. Med. Virol. 83:974–980, 2011.

Ruxolitinib Treatment in a Patient with Primary Myelofibrosis Resistant to Conventional Therapies and Splenectomy: A Case Report.

A 67-year-old male patient who was diagnosed with primary myelofibrosis 4 years ago did not respond to conventional therapies. The splenomegaly progressively increased, which caused spleen infarctions and led to the decision to perform a splenectomy procedure. After splenectomy, the patient started treatment with ruxolitinib. In the first month of ruxolitinib treatment, the patient became transfusion-free and all constitutional symptoms disappeared. However, in the sixth month of ruxolitinib treatment, the disease transformed to acute myeloblastic leukemia, and the patient died 1 month later. This is the first case report that shows the effects of ruxolitinib in a splenectomized patient.

The safety of bortezomib for the treatment of multiple myeloma

ABSTRACT Introduction: There is now 16 years’ worth of established results of various trials demonstrating the bortezomib efficiency in the treatment of multiple myeloma. Over this time, the introduction of bortezomib has been a major break through in the treatment of multiple myeloma. Bortezomib can be administered in the outpatient setting with manageable toxicities. Areas covered: A literature search was carried out using PubMed and Google Scholar. This review gives an overview of the critical role of the bortezomib in multiple myeloma and provides a comprehensive summary of key clinical benefit and safety data with the bortezomib. Initial toxicity profile has improved dramatically with introduction of subcutaneous administration and also, implementation of guidelines for early recognition and treatment. Triplet and quadruplets of bortezomib with agents possessing similar toxicities constitute a challenge. Expert opinion: Bortezomib is an important part of current anti-myeloma therapy with a good clinical efficacy and manageable side effects. Although gastrointestinal disturbances and fatigue are the most common adverse effects, peripheral neuropathy and thrombocytopenia are the key dose-limiting toxicities of bortezomib-based combination regimens. Since these combinations are more effective, with faster disappearance of disease related symptoms and anti-inflammatory effects of bortezomib toxicities were not found to be augmented.

Current Approach to Non-Infectious Pulmonary Complications of Hematopoietic Stem Cell Transplantation

Hematopoietic stem cell transplantation is an established treatment for patients with a wide range of malignant and nonmalignant conditions. Noninfectious pulmonary complications still remain a leading cause of morbidity and mortality in these patients. Treating hematopoietic stem cell transplantation recipients with noninfectious pulmonary complications is still challenging, and the current treatment armamentarium and strategies are not adequate for patients receiving hematopoietic stem cell transplantation. Further trials are needed for a better description of the pathogenesis and the complete diagnostic criteria as well as for the development of effective therapeutic approaches for the management of noninfectious pulmonary complications of the hematopoietic stem cell transplantation. This review outlines the incidence, risk factors, pathogenesis, and clinical spectrum and discusses the current approaches to the management of noninfectious pulmonary complications of Hematopoietic stem cell transplantation.

Gonadotoxic Effects Of Nilotinib In Chronic Myeloid Leukemia Treatment Dose In Mouse Model.

Objective: Tyrosine kinase inhibitors may have deleterious effects on spermatogenesis or folliculogenesis, resulting in male or female subfertility. The aim of this study is to determine the effect of nilotinib, which is used routinely to treat chronic myeloid leukemia, on spermatogenesis and folliculogenesis by using histopathological parameters. Materials and Methods: Ten male and ten female mice were orally treated with nilotinib at 20 mg/kg body weight dissolved in drinking water daily for 2 months. Results: When compared with the control group, a statistically significant decrease was demonstrated in the total follicle numbers of the female mice in the nilotinib group (268±110 vs. 170±60; p=0.03). Active spermatogenesis was observed in each tubule sample taken from the mice in the control and nilotinib groups. Spermatogenic activity was similar in the two groups. Conclusion: We have demonstrated that even though spermatogenesis is preserved, folliculogenesis is inhibited by the usage of a continuous nilotinib treatment dose in chronic myeloid leukemia.

Serum Cystatin C in Patients with Acute Leukemia and its Prognostic Importance

Objective: Serum cystatin C may be over-expressed in some tumour cells and its high serum levels are associated with the poor out come of disease. The aim of this study was to evaluate the serum levels of cystatin-C in acute leukemia patients, explore possible correlations with prognosis. Patients and Methods: Serum samples of patients with newly diagnosis of acute leukemia have been collected at the time of diagnosis from February 2012 until January 2013. Güldane CENGİZ SEVAL1, Tuba CANDAR2, Meltem AYLI3, Çağlar COŞARDERELİOĞLU4, Selda DEMİRTAŞ2, Gülsüm ÖZET5, Simten DAĞDAŞ5, Murat ALBAYRAK6, Harika OKUTAN6 1 Yıldırım Beyazıt Üniversitesi Tıp Fakültesi, Yenimahalle Eğitim ve Araştırma Hastanesi, Hematoloji Bilim Dalı, Ankara, Türkiye 2 Ufuk Üniversitesi Tıp Fakültesi, Biyokimya Anabilim Dalı, Ankara, Türkiye 3 Sağlık Bilimleri Üniversitesi Tıp Fakültesi, Gülhane Eğitim ve Araştırma Hastanesi, Hematoloji Bilim Dalı, Ankara, Türkiye 4 Ufuk Üniversitesi Tıp Fakültesi, İç Hastalıkları Anabilim Dalı, Ankara, Türkiye 5 Ankara Numune Eğitim ve Araştırma Hastanesi, Hematoloji Kliniği, Ankara, Türkiye 6 Ankara Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi, Hematoloji Kliniği, Ankara, Türkiye Uzm. Dr. Güldane CENGİZ SEVAL Yıldırım Beyazıt Üniversitesi Tıp Fakültesi, Yenimahalle Eğitim ve Araştırma Hastanesi, Hematoloji Bilim Dalı, AnkaraTürkiye Geliş: 20.12.2016 Kabul: 24.01.2017 E-posta: guldanecengiz@gmail.com Yazışma Adresi ARAŞTIRMA LLM Dergi 2017;1(1):1-4 • 10.5578/llm.46510 Akut Lösemide Sistatin C’nin Önemi LLM Dergi 2017;1(1):1-4 2 GİRİŞ Sistatin C; 122 aminoasitli, 13 kDa ağırlığında nonglikolize polipeptidli bir sistein proteinaz inhibitörüdür (1). 20. kromozom üzerinde lokalize olan bir “Housekeeping gen” ürünü olup tüm çekirdekli hücrelerde sabit bir hızda üretilir (1). Protein katabolizmasının kontrolünde, hormon sentezinin ve kemik resorbsiyonun düzenlenmesinde, inflamasyon, antijen sunumu ve T hücre bağımlı immün yanıt regülasyonunda rol almaktadır (2,3). Sistatin C’nin belirgin bir diurnal ritmi yoktur. Bütün çekirdekli hücrelerden sabit üretim hızı, renal glomerüllerden serbestçe süzülmesi ve hemen hemen tümünün proksimal tübüllerden geri emilmesi ve kreatininden farklı olarak vücut kas kitlesinden etkilenmemesi nedeniyle glomerüler filtrasyon hızı (GFR)’nın değerlendirilmesi için daha duyarlı bir parametre olduğu birçok çalışmada gösterilmiştir (4). Sistatin C’nin kanser dahil birçok hastalığın proteolitik sistem değişikliği ile ilişkili olduğu ve birçok malignitede de yüksek sistatin C düzeylerinin zararlı tümör ilişkili proteolitik aktiviteyi artırdığı ileri sürülmüştür (5). Kolorektal, akciğer, melanoma karsinomları, multipl miyeloma (MM) ve Hodgkin dışı lenfoma tanısı olan hastalarda, yüksek serum sistatin C seviyelerinin kötü prognozla ilişkisini gösteren çalışmalar vardır (6,7). Sistatin C’nin hepatosellüler kanser olgularında serum seviyesinin yükseldiği ve bir tümör belirteci olarak kullanılabileceği, nozofarengeal karsinomlarda da tanısal ve prognostik değer taşıdığı ve kötü prognostik bir belirteç olduğu bildirilmektedir (8,9). Seksen iki renal fonksiyonları normal sınırlarda olan kanser tanılı hasta ile sağlıklı kontrol grubunun karşılaştırmalı çalışmasında ise kanser grubunda sistatin C düzeylerinin yüksek bulunduğu, bu nedenle kanserli hastalarda renal fonksiyonları göstermede iyi bir belirteç olamayacağı sonucuna varılmıştır (10). İn vitro çalışmalarla da birçok tümör hücresinde sistatin C varlığı gösterilmiştir ve temel hücreden malign hücreye dönüşümün sistatinlerin ekspresyonundaki azalma ile ilişkili olduğu öne sürülmüştür. P-53 mutasyonu olan meme kanseri hücre dizilerinde sistatin C sunumunun azaldığı gösterilmiştir (11). Yine benzer bir çalışma özefagus karsinomu hücre dizilerinde yapılmış ve tümöral hücrelerde azalmış sistatin C sunumunun gösterilmesinin yanı sıra bunun özefagus karsinom hücrelerinin invazyon kabiliyetini inhibe edebileceği yönünde bir sonuç bildirilmiştir (12). Bu nedenle, sistatin C seviyelerinin malignite tanılı, normal renal fonksiyonları olan hastaların takibinde, kemoterapi yanıt değerlendirmede, hastalık sonuçlarını ve prognozu ön görmede kullanılabileceği yönünde görüşler vardır. Literatürde akut lösemi ile sistatin C düzeyleri arasındaki ilişkiye dair veri sınırlıdır. Türkiye’den yapılmış bir çalışmada 19 akut lösemi hastasının pretransplant ve posttransplant sistatin C düzeyleri araştırılmıştır. Bu çalışmada nefrotoksik ilaç kullanımı ile sistatin C yüksekliğindeki paralelliğe dikkat çekilmiştir (13). Biz de bu çalışmamızda; akut lösemi hastalarında, serum sistatin C düzeylerinin ne yönde etkilendiğini, serum sistatin C düzeylerinin tümör yükü, hastalık aktivitesi ve prognoz ile ilişkisini öngörmede kullanılabilecek bir belirteç olup olamayacağını ortaya koymayı amaçladık.