REVIEW | |
1. | Extended Half-Life Coagulation Factors: A New Era in the Management of Hemophilia Patients Muhlis Cem Ar, Can Balkan, Kaan Kavaklı doi: 10.4274/tjh.galenos.2019.2018.0393 Pages 141 - 154 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. |
RESEARCH ARTICLE | |
2. | Long-term Dental Anomalies after Pediatric Cancer Treatment in Children Gülser Kılınç, Gülçin Bulut, Fahinur Ertuğrul, Hale Ören, Bengü Demirağ, Ayşe Demiral, Serap Aksoylar, Emine Serra Kamer, Hülya Ellidokuz, Nur Olgun doi: 10.4274/tjh.galenos.2018.2018.0248 Pages 155 - 161 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. |
3. | Ortho-Topolin Riboside Induced Differentiation through Inhibition of STAT3 Signaling in Acute Myeloid Leukemia HL-60 Cells Li Wang, Jiao Cheng, Fanlin Lin, Shengxian Liu, Hui Pan, Mingda Li, Shanshan Li, Na Li, Weiping Li doi: 10.4274/tjh.galenos.2019.2019.0020 Pages 162 - 168 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. |
4. | Acute Lymphoblastic Leukemia in Routine Practice: A Turkish Multicenter Study Rafiye Çiftçiler, Omur Gokmen Sevindik, Ali İrfan Emre Tekgündüz, Mehmet Ali Ertürk, Filiz Vural, Burhan Turgut, Leylagül Kaynar, Bahriye Payzın, Mehmet Hilmi Doğu, Volkan Karakuş, Fevzi Altuntaş, Yahya Büyükaşık, Fatih Demirkan doi: 10.4274/tjh.galenos.2019.2019.0008 Pages 169 - 177 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. |
5. | The Role of the Local Bone Marrow Renin-Angiotensin System in Multiple Myeloma Bülent Saka, Müge Sayitoğlu, Zülal İstemihan, Mehmet Akif Karan, Sebile Nilgün Erten, Öner Doğan, Uğur Özbek, Sema Genç, Cemil Taşçıoğlu, Sevgi Kalayoğlu Beşışık doi: 10.4274/tjh.galenos.2019.2018.0420 Pages 178 - 185 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. |
6. | The Use of Allogeneic Mesenchymal Stem Cells in Childhood Steroid-Resistant Acute Graft-Versus-Host Disease: A Retrospective Study of a Single-Center Experience Ceyhun Bozkurt, Erdal Karaöz, Başak Adaklı Aksoy, Selime Aydoğdu, Tunç Fışgın doi: 10.4274/tjh.galenos.2019.2019.0090 Pages 186 - 192 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. |
BRIEF REPORT | |
7. | Effectiveness of Sequential Compression Devices in Prevention of Venous Thromboembolism in Medically Ill Hospitalized Patients: A Retrospective Cohort Study Prajwal Dhakal, Ling Wang, Joseph Gardiner, Shiva Shrotriya, Mukta Sharma, Supratik Rayamajhi doi: 10.4274/tjh.galenos.2019.2018.0413 Pages 193 - 198 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. |
IMAGES IN HEMATOLOGY | |
8. | A Case of Anaplastic Lymphoma Kinase-positive Large B-cell Lymphoma Gaurav Gupta, Monika Pilichowska doi: 10.4274/tjh.galenos.2019.2019.0064 Pages 199 - 200 Abstract | |
9. | Blastic Plasmacytoid Dendritic Cell Neoplasm with Leukemic Component Maria Jimenez doi: 10.4274/tjh.galenos.2019.2018.0363 Pages 201 - 202 Abstract | |
10. | Vacuolization in Myeloid and Erythroid Precursors in a Child with Menkes Disease Seçil Sayın, Şule Ünal, Mualla Çetin, Fatma Gümrük doi: 10.4274/tjh.galenos.2018.2018.0104 Pages 203 - 204 Abstract | |
LETTER TO EDITOR | |
11. | Pediatric Deep Venous Thrombosis and Pulmonary Embolism: Can It Be Antiphospholipid Syndrome? Fatma Demir Yenigürbüz, Hale Ören doi: 10.4274/tjh.galenos.2018.2018.0214 Pages 205 - 221 Abstract | |
12. | Pediatric Chronic Myeloid Leukemia Presenting in a Mixed Phenotypic Blast Crisis: A Rare Occurrence Jenna Bhattacharya, Richa Gupta doi: 10.4274/tjh.galenos.2019.2018.0428 Pages 206 - 208 Abstract | |
13. | Myeloid Sarcoma of the Parotid Gland and Stomach Presenting with Obstructive Jaundice: A Rare Presentation Sugeeth M Thambi, Sreejith G Nair, Rony Benson, Jayasudha A Vasudevan, Rekha A Nair doi: 10.4274/tjh.galenos.2019.2018.0302 Pages 208 - 210 Abstract | |
14. | An Unusual Presentation of Hairy Cell Leukemia Smeeta Gajendra, Bhawna Jha, Sarita Prasad, Pratibha Dhiman, Manorama Bhargava doi: 10.4274/tjh.galenos.2019.2018.0304 Pages 210 - 211 Abstract | |
15. | Megakaryocytes in Peripheral Blood Smears Neha Garg, Rashmi Jain Gupta, Sunil Kumar doi: 10.4274/tjh.galenos.2019.2019.0022 Pages 212 - 213 Abstract | |
16. | Outcome of Thrombotic Thrombocytopenic Purpura Patients: A Single-Center Experience Özcan Çeneli, Seda Yılmaz, Mehmet Ali Karaselek, Kazım Çamlı doi: 10.4274/tjh.galenos.2019.2019.0048 Pages 214 - 215 Abstract | |
17. | Severe Bone Marrow Hypoplasia with Black Cumin (Nigella sativa) Ingestion in a Patient with T-ALL in First Complete Remission Zehra Narlı Özdemir, Cemaleddin Öztürk, Işınsu Kuzu, Muhit Özcan doi: 10.4274/tjh.galenos.2019.2019.0093 Pages 215 - 217 Abstract | |
18. | Tumor Lysis Syndrome Due to Targeting of Hepatocellular Carcinoma Associated with Chronic Myelomonocytic Leukemia Müfide Okay, Sıla Çetik, İbrahim C. Haznedaroğlu doi: 10.4274/tjh.galenos.2019.2019.0113 Pages 218 - 219 Abstract | |
19. | MDM2 Oncogene Copy Number Alterations in Chronic Lymphocytic Leukemia Pathum Sookaromdee, Viroj Wiwanitkit doi: 10.4274/tjh.galenos.2019.2019.0179 Pages 220 - 221 Abstract | |