REVIEW | |
1. | Clinical Interpretation of Genomic Variations Müge Sayitoğlu doi: 10.4274/tjh.2016.0149 Pages 172 - 179 Novel high-throughput sequencing technologies generate largescale genomic data and are used extensively for disease mapping of monogenic and/or complex disorders, personalized treatment, and pharmacogenomics. Next-generation sequencing is rapidly becoming routine tool for diagnosis and molecular monitoring of patients to evaluate therapeutic efficiency. The next-generation sequencing platforms generate huge amounts of genetic variation data and it remains a challenge to interpret the variations that are identified. Such data interpretation needs close collaboration among bioinformaticians, clinicians, and geneticists. There are several problems that must be addressed, such as the generation of new algorithms for mapping and annotation, harmonization of the terminology, correct use of nomenclature, reference genomes for different populations, rare disease variant databases, and clinical reports. |
RESEARCH ARTICLE | |
2. | The Mutation Profile of Calreticulin in Patients with Myeloproliferative Neoplasms and Acute Leukemia Jingyi Wang, Jianguo Hao, Na He, Chunyan Ji, Daoxin Ma doi: 10.4274/tjh.2015.0220 Pages 180 - 186 Objective: Calreticulin (CALR) plays important roles in cell proliferation, apoptosis, and immune responses. CALR mutations were described recently in Janus kinase 2 gene (JAK2)-negative or MPLnegative primary myelofibrosis (PMF) and essential thrombocythemia (ET) patients. CALR trails JAK2 as the second most mutated gene in myeloproliferative neoplasms (MPNs). However, little is known about CALR mutation in Chinese patients with leukemia. In the present study, a cohort of 305 Chinese patients with hematopoietic neoplasms was screened for CALR mutations, with the aim of uncovering the frequency of CALR mutations in leukemia and MPNs. Materials and Methods: Polymerase chain reaction and direct sequencing were performed to analyze mutations of CALR in 305 patients with hematopoietic malignancies, including 135 acute myeloid leukemia patients, 57 acute lymphoblastic leukemia patients, and 113 MPN patients. Results: CALR mutations were found in 10.6% (12 of 113) of samples from patients with MPNs. CALR mutations were determined in 11.3% (6 of 53), 21.7% (5 of 23), and 9.1% (1/11) of patients with ET, PMF, and unclassifiable MPN, respectively. Conclusion: We showed that MPN patients carrying CALR mutations presented with higher platelet counts and lower hemoglobin levels compared to those with mutated JAK2. However, all of the leukemia patients had negative results for CALR mutations. |
3. | Clinical Features of 294 Turkish Patients with Chronic Myeloproliferative Neoplasms Neslihan Andıç, Mustafa Ünübol, Eren Yağcı, Olga Meltem Akay, İrfan Yavaşoğlu, Vefki Gürhan Kadıköylü, Ali Zahit Bolaman doi: 10.4274/tjh.2015.0041 Pages 187 - 195 Objective: Myeloproliferative neoplasms (MPNs) share common clonal stem cells but show significant differences in their clinical courses. The aim of this retrospective study was to evaluate thrombotic and hemorrhagic complications, JAK2 status, gastrointestinal and cardiac changes, treatment modalities, and survival in MPNs in Turkish patients. Materials and Methods: Medical files of 294 patients [112 essential thrombocythemia (ET), 117 polycythemia vera (PV), 46 primary myelofibrosis, and 19 unclassified MPN cases] from 2 different universities in Turkey were examined. Results: Older age, higher leukocyte count at diagnosis, and JAK2 mutation positivity were risk factors for thrombosis. Platelet count over 1000x109/L was a risk factor for hemorrhagic episodes. Hydroxyurea treatment was not related to leukemic transformation. Median follow-up time was 50 months (quartiles: 22.2-81.75) in these patients. Patients with primary myelofibrosis had the shortest survival of 137 months when compared with 179 months for ET and 231 months for PV. Leukemic transformation, thromboembolic events, age over 60 years, and anemia were found to be the factors affecting survival. Conclusion: Thromboembolic complications are the most important preventable risk factors for morbidity and mortality in MPNs. Drug management in MPNs is done according to hemoglobin and platelet counts. Based on the current study population our results support the idea that leukocytosis and JAK2 positivity are more important risk factors for thrombosis than hemoglobin and platelet values. |
4. | Retrospective Study of Incidence and Prognostic Significance of Eosinophilia after Allogeneic Hematopoietic Stem Cell Transplantation: Influence of Corticosteroid Therapy Wataru Yamamoto, Eriko Ogusa, Kenji Matsumoto, Atsuo Maruta, Yoshiaki Ishigatsubo, Heiwa Kanamori doi: 10.4274/tjh.2015.0047 Pages 196 - 201 Objective: The clinical significance of eosinophilia after allogeneic hematopoietic stem cell transplantation is controversial. This study aimed to retrospectively study the impact of eosinophilia on the outcome of allogeneic hematopoietic stem cell transplantation by taking into account the influence of corticosteroid therapy. Materials and Methods: We retrospectively studied 204 patients with acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome who underwent allogeneic hematopoietic stem cell transplantation from January 2001 to December 2010. Results: The median age was 43 years (minimum-maximum: 17- 65 years). Myeloablative conditioning was used in 153 patients and reduced intensity conditioning was employed in 51 patients. Donor cells were from bone marrow in 132 patients, peripheral blood in 34, and cord blood in 38. Eosinophilia was detected in 71 patients and there was no significant predictor of eosinophilia by multivariate analysis. There was no relationship between occurrence of eosinophilia and the incidence or grade of acute graft-versus-host disease when the patients were stratified according to corticosteroid treatment. Although eosinophilia was a prognostic factor for 5-year overall survival by univariate analysis, it was not a significant indicator by multivariate analysis. Conclusion: These results suggest that the clinical significance of eosinophilia in patients receiving allogeneic hematopoietic stem cell transplantation should be assessed with consideration of systemic corticosteroid administration. |
5. | Cytokine Contents in Chronic Lymphocytic Leukemia: Association with ZAP70 Expression Nilgün Işıksaçan, Suzan Çınar, Esin Aktaş Çetin, Melih Aktan, Günnur Deniz doi: 10.4274/tjh.2014.0469 Pages 202 - 208 Objective: Chronic lymphocytic leukemia (CLL) is a disease that shows varying clinical progression, and expression of the protein tyrosine kinase ZAP70 has been described as a very valuable prognostic factor. Patients with ZAP70 positivity are characterized by worse clinical course and significantly shorter progression-free and overall survival. In this study, intracytoplasmic interferon gamma (IFN-γ) and interleukin-4 (IL-4) content of T, B, and CLL cells in CLL patients and their correlations with Rai staging and ZAP70 positivity were investigated. Materials and Methods: CLL patients newly diagnosed or in followup at the İstanbul University İstanbul Medical Faculty Hematology Department were included in this study. These patients were classified according to Rai staging and ZAP70 expression. IL-4, IFN-γ, and ZAP70 expressions in peripheral blood T, B, and CLL cells were measured by four-color flow cytometry. Results: There was a statistically significant correlation between advanced disease and ZAP70 positivity. IL-4-secreting T cells were significantly increased; however, IFN-γ secretion was significantly decreased in CLL patients compared to healthy individuals, whereas IL-4-secreting B cells were significantly diminished in contrast to T cells. Conclusion: These findings suggest damage in the cellular immunity and that IL-4 might lead to many complications and may be important in disease progression. |
6. | Finding the Optimal Conditioning Regimen for Relapsed/Refractory Lymphoma Patients Undergoing Autologous Hematopoietic Cell Transplantation: A Retrospective Comparison of BEAM and High-Dose ICE Onur Esbah, Emre Tekgündüz, Itır Şirinoğlu Demiriz, Sinem Civriz Bozdağ, Ali Kaya, Ayşegül Tetik, Ömür Kayıkçı, Gamze Durgun, Şerife Kocubaba, Fevzi Altuntaş doi: 10.4274/tjh.2014.0214 Pages 209 - 215 Objective: High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHCT) is a well-defined treatment modality for relapsed/refractory non-Hodgkin’s lymphoma (NHL) and Hodgkin’s lymphoma (HL). Although there are several options in terms of conditioning regimens before AHCT, no one treatment is accepted as a standard of care. This study aimed to compare different conditioning regimens for the treatment of NHL and HL. Materials and Methods: Medical records of 62 patients who had undergone AHCT following BEAM (BCNU, etoposide, cytarabine, and melphalan) and high-dose ICE (hICE; ifosfamide, carboplatin, and etoposide) conditioning regimens were analyzed retrospectively and compared in terms of efficacy and adverse effects. Results: The study included a total of 29 and 33 patients diagnosed with relapsed/refractory NHL and HL, respectively. Patients received BEAM (n=37) or hICE (n=25) regimens for conditioning. One-year overall survival was 73±6% in all patients. One-year overall survival was 71±8% and 74±9% in the BEAM and hICE groups, respectively (p=0.86). The incidences of nausea/vomiting (grade ≥2) (84% vs. 44.7%; p=0.04) and mucositis (grade ≥2) (13% vs. 3%; p=0.002) were higher in the hICE group compared to the BEAM group. In addition, we witnessed significantly more hepatotoxicity of grade ≥2 (40% vs. 2.7%; p<0.005) and nephrotoxicity of grade ≥2 (48% vs. 2.7%; p<0.005) among patients who received hICE. Significantly more patients (n=4; 25%) in the hICE group experienced veno-occlusive disease (VOD) compared to the BEAM arm, where no patients developed VOD (p=0.01). Conclusion: There was no difference in terms of overall survival between the BEAM and hICE groups. We observed significantly more adverse effects among patients treated with hICE. The BEAM regimen seems to be superior to hICE in terms of toxicity profile with comparable efficacy in patients with relapsed/refractory NHL and HL. |
7. | The Changing Epidemiology of Bloodstream Infections and Resistance in Hematopoietic Stem Cell Transplantation Recipients Mücahit Yemişen, İlker İnanç Balkan, Ayşe Salihoğlu, Ahmet Emre Eskazan, Bilgül Mete, M. Cem Ar, Şeniz Öngören, Zafer Başlar, Reşat Özaras, Neşe Saltoğlu, Ali Mert, Burhan Ferhanoğlu, Recep Öztürk, Fehmi Tabak, Teoman Soysal doi: 10.4274/tjh.2014.0378 Pages 216 - 222 Objective: Patients receiving hematopoietic stem cell transplantation (HSCT) are exposed to highly immunosuppressive conditions and bloodstream infections (BSIs) are one of the most common major complications within this period. Our aim, in this study, was to evaluate the epidemiology of BSIs in these patients retrospectively. Materials and Methods: The epidemiological properties of 312 patients with HSCT were retrospectively evaluated. Results: A total of 312 patients, followed between 2000 and 2011, who underwent autologous (62%) and allogeneic (38%) HSCT were included in the study. The most common underlying malignancies were multiple myeloma (28%) and Hodgkin lymphoma (21.5%). A total of 142 (45%) patients developed at least 1 episode of BSI and 193 separate pathogens were isolated from the blood cultures. There was a trend of increase in the numbers of BSIs in 2005-2008 and a relative increase in the proportion of gram-positive infections in recent years (2009-2011), and central venous catheter-related BSI was found to be most common source. Coagulase-negative staphylococci (49.2%) and Acinetobacter baumannii (8.8%) were the most common pathogens. Extended-spectrum beta-lactamase-producing strains were 23% and 22% among Escherichia coli and Klebsiella spp. isolates, respectively. Quinolone resistance was detected in 10% of Enterobacteriaceae. Resistance to carbapenems was not detected in Enterobacteriaceae, while it was seen at 11.1% and 23.5% in Pseudomonas and Acinetobacter strains, respectively. Conclusion: A shift was detected from gram-negative bacteria to gram-positive in the etiology over the years and central lines were the most common sources of BSIs. |
8. | BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment Young Hoon Park, Joo Han Lim, Hyeon Gyu Yi, Moon Hee Lee, Chul Soo Kim doi: 10.4274/Tjh.2015.0131 Pages 223 - 230 Objective: BK virus-hemorrhagic cystitis (BKV-HC) is a potential cause of morbidity and mortality in patients having undergone allogeneic stem cell transplantation (Allo-SCT). We analyzed the clinical features of BKV-HC following Allo-SCT and reported the utility of leflunomide therapy for BKV-HC. Materials and Methods: From January 2005 to June 2014, among the 69 patients that underwent Allo-SCT in our institution, the patients who experienced BKV-HC were investigated retrospectively. Results: HC was observed in 30 patients (43.5%), and among them, 18 of the cases (26.1%) were identified as BKV-HC. The median age of the patients (12 males and 6 females) was 45 years (minimum-maximum: 13-63). Patients received Allo-SCT for acute myeloid leukemia (n=11), aplastic anemia (n=4), myelodysplastic syndrome (n=2), and non-Hodgkin lymphoma (n=1). The donor types were human leukocyte antigen (HLA)-matched sibling donor for six patients, HLA-matched unrelated donor for nine, and haploidentical familial donor for two. The median onset and duration of BKV-HC was on day 21 after transplantation (minimum-maximum: 7-97) and 22 days (minimum-maximum: 6-107). Eleven patients (62.1%) had grade I-II HC and seven patients (38.9%) had grade III-IV (high-grade) HC. Among the seven patients who had high-grade HC, one had complete response, one had partial response, and five had no response. Among the five nonresponders, one died of BKV-HC associated complications. The remaining four patients were treated with leflunomide, achieving complete response (n=2) and partial response (n=2). The median duration from the start of leflunomide therapy to response was 13 days (minimum-maximum: 8-17 days). All patients tolerated the leflunomide treatment well, with three patients having mild gastrointestinal symptoms, including anorexia and abdominal bloating. Conclusion: BKV-HC was commonly observed in patients with HC following Allo-SCT. In high-grade BKV-HC patients who do not respond to supportive care, leflunomide may be a feasible option without significant toxicity. |
9. | A Randomized Study Comparing the Efficacy of Three Hepatitis B Vaccine Induction Regimens in Adult Patients with Hematological Malignancies Zübeyde Nur Özkurt, Elif Suyanı, Rauf Haznedar, Münci Yağcı doi: 10.4274/tjh.2015.0079 Pages 231 - 235 Objective: Non-responsiveness to hepatitis B virus (HBV) vaccines is not rare in hemato-oncological patients due to disease-associated or treatment-induced immune suppression. Although different strategies have been employed to improve the response rates, to date there is not an approved schedule for HBV immunization in patients with hematological malignancies. We designed a prospective randomized study to evaluate the efficacy of 3 different induction regimens for HBV vaccination. Materials and Methods: In the standard-dose (SD) group, total vaccine dose delivered was 40 μg and patients were vaccinated with 20 μg at weeks 0 and 4. In the high-dose dose-intensive (HDDI) group, total vaccine dose delivered was 80 μg and patients were vaccinated with 40 μg at weeks 0 and 4. In the high-dose time-intensive (HDTI) group, total vaccine dose delivered was 80 μg and patients were vaccinated with 20 μg at weeks 0, 2, 4, and 6. Results: In a cohort of 114 patients, 38.6% responded to HBV vaccination. The response rate in the SD arm, HDDI arm, and HDTI arm was 26.2%, 29.7%, and 44.4%, respectively (p>0.05). Age was the only variable identified as having a negative impact on response. Conclusion: Short of achieving statistical significance, a higher response rate was observed in the HDTI arm. Therefore, this study supports a high-dose, time-intensive HBV vaccine induction regimen in patients with hematological malignancies who are not on chemotherapy. |
10. | Reliability and Validity of the Turkish Version of the PedsQL 3.0 Cancer Module for 2- to 7-Year-Old and the PedsQL 4.0 Generic Core Scales for 5- to 7-Year-Old: The Hacettepe University Experience Vesile Yıldız Kabak, Yavuz Yakut, Mualla Çetin, Tülin Düger doi: 10.4274/tjh.2015.0242 Pages 236 - 243 Objective: The aim of this study was to investigate the reliability and validity of the Turkish version of the Pediatric Quality of Life Inventory (PedsQL) 3.0 Cancer Module for 2- to 7-year-old and the PedsQL 4.0 Generic Core Scales for 5- to 7-year-old in childhood cancer. Materials and Methods: The PedsQL 3.0 Cancer Module and PedsQL 4.0 Generic Core Scales were administered to children with cancer and their parents at Hacettepe University. Internal consistency was determined by using Cronbach’s alpha and test-retest reliability was determined by using the intraclass correlation coefficient (ICC). Construct validity was assessed by comparing the results of the PedsQL 3.0 Cancer Module with those of the PedsQL 4.0 Generic Core Scales. Results: Cronbach’s alpha of the PedsQL 3.0 Cancer Module varied from 0.803 to 0.873 and that of the PedsQL 4.0 Generic Core Scales from 0.665 to 0.841. Test-retest ICC values of the PedsQL 3.0 Cancer Module varied from 0.877 to 0.949 and those of the PedsQL 4.0 Generic Core Scales from 0.681 to 0.824. The correlation of the PedsQL 3.0 Cancer Module with subscale scores of the PedsQL 4.0 Generic Core Scales showed that there were excellent to fair correlations between the two scales. The relationship between parent proxy-report and child self-report of the PedsQL 3.0 Cancer Module had very good correlation (r=0.694, p<0.001), as did the PedsQL 4.0 Generic Core Scales (r=0.540, p=0.002). Conclusion: This study demonstrated the reliability, validity, and feasibility of the Turkish version of the PedsQL 3.0 Cancer Module in 2- to 4-year-old and 5- to 7-year-old and the PedsQL 4.0 Generic Core Scales in 5- to 7-year-old in childhood cancer. |
BRIEF REPORT | |
11. | Results of Four-Year Rectal Vancomycin-Resistant Enterococci Surveillance in a Pediatric Hematology-Oncology Ward: From Colonization to Infection Hacer Aktürk, Murat Sütçü, Ayper Somer, Serap Karaman, Manolya Acar, Ayşegül Ünüvar, Sema Anak, Zeynep Karakaş, Aslı Özdemir, Kutay Sarsar, Derya Aydın, Nuran Salman doi: 10.4274/tjh.2015.0368 Pages 244 - 247 Objective: To investigate the clinical impact of vancomycinresistant enterococci (VRE) colonization in patients with hematologic malignancies and associated risk factors. Materials and Methods: Patients colonized and infected with VRE were identified from an institutional surveillance database between January 2010 and December 2013. A retrospective case-control study was performed to identify the risk factors associated with development of VRE infection in VRE-colonized patients. Results: Fecal VRE colonization was documented in 72 of 229 children (31.4%). Seven VRE-colonized patients developed subsequent systemic VRE infection (9.7%). Types of VRE infections included bacteremia (n=5), urinary tract infection (n=1), and meningitis (n=1). Enterococcus faecium was isolated in all VRE infections. Multivariate analysis revealed severe neutropenia and previous bacteremia with another pathogen as independent risk factors for VRE infection development in colonized patients [odds ratio (OR): 35.4, confidence interval (CI): 1.7-72.3, p=0.02 and OR: 20.6, CI: 1.3-48.6, p=0.03, respectively]. No deaths attributable to VRE occurred. Conclusion: VRE colonization has important consequences in pediatric cancer patients. |
12. | Radiation-Induced Tumor Lysis Syndrome in Chronic Lymphocytic Leukemia Ali Alkan, Tuğçe Kütük, Ebru Karcı, Arzu Yaşar, Ayşe Hiçsönmez, Güngör Utkan doi: 10.4274/tjh.2015.0259 Pages 248 - 250 Tumor lysis syndrome (TLS) is an important oncological emergency that is usually observed with hematological malignancies and rarely with solid tumors. It can be induced either by therapy or spontaneously. Radiotherapy-induced TLS has been rarely reported in the literature. Here we present a patient with a diagnosis of metastatic prostate cancer and chronic lymphocytic leukemia complicated with TLS during palliative radiotherapy. |
13. | A Case of Superwarfarin Poisoning Due to Repetitive Occupational Dermal Rodenticide Exposure in a Worker Narlı Zehra Özdemir, Uğur Şahin, Mustafa Merter, Mehmet Gündüz, Berna Ateşağaoğlu, Meral Beksaç doi: 10.4274/tjh.2015.0433 Pages 251 - 253 Superwarfarin poisoning is usually due to chronic occult small-dose exposures and can easily be misdiagnosed and may lead to serious complications. The diagnosis can be confirmed by a concordant history and analyses of blood and urine specimens with the liquid chromatography with tandem mass spectrometry (LC-MS/MS) technique. Several months of continuous treatment with high doses of daily oral vitamin K, as well as other supportive measures, are warranted, especially when repeated laboratory measurements to help predict the treatment period are not available. In this paper, a case of superwarfarin poisoning due to chronic repetitive occupational dermal exposure to commercial rodenticides is presented. |
LETTER TO EDITOR | |
14. | A Primary Bone Diffuse Large B-Cell Lymphoma with Ocular Adnexal Involvement Rafet Eren, Ceyda Aslan, Cihan Gündoğan, Osman Yokuş, Mehmet Hilmi Doğu, Elif Suyanı doi: 10.4274/tjh.2015.0424 Pages 254 - 255 Abstract | |
15. | Cerebral Sinovenous Thrombosis Mimicking Intracranial Mass Derya Özyörük, Neslihan Karakurt, Arzu Yazal Erdem, Suna Emir, Bahattin Tunç, Neşe Yaralı, Namık Özbek doi: 10.4274/tjh.2016.0038 Pages 255 - 256 Abstract | |
16. | A Rare Cause of Unexplained Refractory Iron Deficiency Anemia: Unicentric Plasma-Cell Type Castleman’s Disease Sevgi Kalayoğlu Beşışık, İpek Yönal Hindilerden, Fehmi Hindilerden, İbrahim Öner Doğan, Fatih Beşışık doi: 10.4274/tjh.2016.0083 Pages 257 - 258 Abstract | |
IMAGES IN HEMATOLOGY | |
17. | Vaginal Lymphoma: A Possible Cause of Genital Hemorrhage Erdoğan Nohuz, Sharif Kullab, Albane Ledoux - Pilon, Cécile Moluçon - Chabrot, Maël Albaut, Luisa De Simone, Xavier Durando doi: 10.4274/tjh.2015.0112 Pages 259 - 260 Abstract | |
18. | Endothelial Cells, Ankaferd Hemostat, and Estradiol Yasemin Ardıçoğlu, Nejat Akar, İbrahim Haznedaroğlu doi: 10.4274/tjh.2015.0143 Pages 261 - 262 Abstract | |
19. | An Unusual Congenital Anomaly in Fanconi Aplastic Anemia: Congenital Lobar Emphysema Ali Fettah, Gökçe Pınar Reis, Soner Sertan Kara, Tekin Aksu, Afak Durur Karakaya, Mahmut Subaşı, Atilla Çayır doi: 10.4274/tjh.2015.0384 Pages 263 - 264 Abstract | |