E-ISSN: 1308-5263
Turkish Journal of Hematology - Turk J Hematol: 34 (4)
Volume: 34  Issue: 4 - 2017
REVIEW
1. The Scope of Kidney Affection in Monoclonal Gammopathies at All Levels of Clinical Significance
Şadiye Mehtat Ünlü, Hayri Özsan, Sülen Sarıoğlu
doi: 10.4274/tjh.2017.0197  Pages 282 - 288
Multiple myeloma (MM) is one of the most important clonal malignant plasma cell disorders and renal involvement is associated with poor prognosis. Although there are several reasons for renal impairment in MM, the main cause is the toxic effects of monoclonal proteins. Although cast nephropathy is the best known and unchallenged diagnosis for hematologists and pathologists, the renal effects of monoclonal gammopathy can be various. Monoclonal gammopathy of renal significance was proposed by the International Kidney and Monoclonal Gammopathy Research Group for renal lesions in monoclonal gammopathy in recent years. Renal lesions in monoclonal gammopathy can be grouped as follows: light chain (cast) nephropathy, acute tubular injury/necrosis, tubulointerstitial nephritis, amyloidosis, monoclonal Ig deposition diseases, immunotactoid glomerulopathy, type I cryoglobulinemia, proliferative glomerulonephritis with monoclonal IgG deposits, C3 glomerulopathy with monoclonal gammopathy, and crystal-storing histiocytosis, considering the previous and new terminology. In this study, renal involvement of monoclonal gammopathies, in terms of previous and new terminology, was reviewed.

COMMENTARY
2. Time to Cure Hairy Cell Leukemia
Ilana Levy, Tamar Tadmor
doi: 10.4274/tjh.2017.0296  Pages 289 - 290
Abstract |Full Text PDF

RESEARCH ARTICLE
3. Retrospective Evaluation of Hairy Cell Leukemia Patients Treated with Three Different First-Line Treatment Modalities in the Last Two Decades: A Single-Center Experience
Şeniz Öngören, Ahmet Emre Eşkazan, Selin Berk, Tuğrul Elverdi, Ayşe Salihoğlu, Muhlis Cem Ar, Zafer Başlar, Yıldız Aydın, Nükhet Tüzüner, Teoman Soysal
doi: 10.4274/tjh.2016.0443  Pages 291 - 299
Objective: In this study, we retrospectively analyzed the clinical outcome, treatment responses, infectious complications, and survival rates of 71 hairy cell leukemia (HCL) cases.
Materials and Methods: Sixty-seven patients received a first-line treatment and 2-chlorodeoxyadenosine (cladribine-2-CdA) was administered in 31 cases, 19 patients received interferon-alpha (INF-α), splenectomy was performed in 16 cases, and rituximab was used in one.
Results: Although the highest overall response rate (ORR) was observed in patients receiving 2-CdA upfront, ORRs were comparable in the 2-CdA, INF-α, and splenectomy subgroups. Relapse rates were significantly lower in patients who received first-line 2-CdA. The progression-free survival (PFS) rate with 2-CdA was significantly higher than in patients with INF-α and splenectomy, but we found similar overall survival rates with all three upfront treatment modalities. Infections including tuberculosis were a major problem.
Conclusion: Although purine analogues have improved the ORRs and PFS, there is still much progress to make with regard to overall survival and relapsed/refractory disease in patients with HCL.

4. FMS-Like Tyrosine Kinase 3 ( FLT3 ) and Nucleophosmin 1 ( NPM1 ) in Iranian Adult Acute Myeloid Leukemia Patients with Normal Karyotypes: Mutation Status and Clinical and Laboratory Characteristics
Narges Rezaei, Nargess Arandi, Behnaz Valibeigi, Sezaneh Haghpanah, Mehdi Khansalar, Mani Ramzi
doi: 10.4274/tjh.2016.0489  Pages 300 - 306
Objective: In this study, we evaluated the frequency of FMS-like tyrosine kinase 3 (FLT3-ITD and FLT3-TKD) and nucleophosmin (NPM1) mutations in Iranian patients with cytogenetically normal acute myeloid leukemia (CN-AML). The clinical and laboratory characteristics were compared between wild-type and mutant cases.
Materials and Methods: Seventy newly diagnosed de novo AML patients were recruited at the time of diagnosis prior to chemotherapy; among them, 54 had CN-AML. For detecting mutations, the FLT3 and NPM1 genes were amplified by the polymerase chain reaction method, followed by direct sequencing.
Results: Our results showed that the frequencies of FLT3-ITD, FLT3TKD, and NPM1 mutations in CN-AML patients were 25.9%, 5.9%, and 20.8%, respectively. The most frequent NPM1 mutation type was the type A mutation. The FLT3-ITD mutation was seen more frequently in non-M3 patients compared with M3 patients. No mutation was observed in either the FLT3-TKD or the NPM1 gene in patients in the M3 French-American-British group. There was no significant association between the presence of FLT3-ITD and NPM1 mutations in CN-AML patients (p>0.05). The frequency of FLT3-ITD, FLT3-TKD, and NPM1 mutation was higher in CN-AML patients in comparison with AML patients with cytogenetic aberrations, although the differences were not statistically significant (p>0.05). There were no significant differences in mean white blood cell and platelet counts, serum hemoglobin levels, and bone marrow blast percentages between patients with wild-type and mutant FLT3-ITD and NPM1 genes (p>0.05). No difference was observed in the frequency of FLT3-ITD or NPM1 mutation regarding age or sex (p>0.05).
Conclusion: Given the high stability of NPM1 during the disease course, it can be used in combination with FLT3 as well as other known genetic markers to monitor patients, especially for minimal residual disease detection.

5. Autoantibodies Against Carbonic Anhydrase I and II in Patients with Acute Myeloid Leukemia
Ahmet Menteşe, Nergiz Erkut, Selim Demir, Serap Özer Yaman, Aysegül Sümer, Seniz Doğramacı, Ahmet Alver, Mehmet Sönmez
doi: 10.4274/tjh.2016.0341  Pages 307 - 313
Objective: Cancer, one of the principal causes of death, is a global social health problem. Autoantibodies developed against the organism’s self-antigens are detected in the sera of subjects with cancer. In recent years carbonic anhydrase (CA) I and II autoantibodies have been shown in some autoimmune diseases and carcinomas, but the mechanisms underlying this immune response have not yet been explained. The aim of this study was to evaluate CA I and II autoantibodies in patients with acute myeloid leukemia (AML) and to provide a novel perspective regarding the autoimmune basis of the disease.
Materials and Methods: Anti-CA I and II antibody levels were investigated using ELISA in serum samples from 30 patients with AML and 30 healthy peers.
Results: Anti-CA I and II antibody titers in the AML group were significantly higher compared with the control group (p=0.0001 and 0.018, respectively). A strong positive correlation was also determined between titers of anti-CA I and II antibodies (r=0.613, p=0.0001).
Conclusion: Our results suggest that these autoantibodies may be involved in the pathogenesis of AML. More extensive studies are now needed to reveal the entire mechanism.

6. Flow Cytometric Aldehyde Dehydrogenase Assay Enables a Fast and Accurate Human Umbilical Cord Blood Hematopoietic Stem Cell Assessment
Emine Begüm Gencer, Pınar Yurdakul, Klara Dalva, Meral Beksaç
doi: 10.4274/tjh.2016.0214  Pages 314 - 320
Objective: Colony-forming units of granulocytes/macrophages (CFU-GM) analysis is the most widely used method to determine the hematopoietic stem cell (HSC) content of human umbilical cord blood (CB) for prediction of engraftment potential. The measurement of aldehyde dehydrogenase (ALDH) activity is a more recent method for HSC qualification. Our aim was to correlate phenotypic and functional assays to find the most predictive method. 
Materials and Methods: In this study, flow cytometric quantitation of CD34+ cells and ALDH positivity along with CFU-GM capacity were assessed in fresh and post-thaw CB units.
Results: Among 30 post-processing samples, for each CB unit the mean total number of nucleated cells (TNCs) was (93.8±30.1)x107, CD34+ cells were (3.85±2.55)x106, ALDH+ cells were (3.14±2.55)x106, and CFU-GM count was (2.64±1.96)x105. Among an additional 19 postthaw samples the cell counts were as follows: TNCs, (32.79±17.27)x107; CD34+, (2.18±3.17)x106; ALDH+, (2.01±2.81)x106; CFU-GM, (0.74±0.92) x105. Our findings showed that in fresh samples TNCs, CD34+ cells, and ALDH correlated highly with counts of CFU-GM, CFU-erythroids/ granulocytes-macrophages/megakaryocytic cells (GEMM), and burst forming units of erythroids (BFU-E) as follows: TNCs, r=0.47, r=0.35, r=0.41; CD34+, r=0.44, r=0.54, r=0.41; and ALDH, r=0.63, r=0.45, r=0.6, respectively. In terms of post-thaw samples, the correlations were as follows: TNCs, r=0.59, r=0.46, r=0.56; CD34+, r=0.67, r=0.48, r=0.61; and ALDH, r=0.61, r=0.67, r=0.67, for CFU-GM, CFU-GEMM, and BFU-E, respectively. All correlations were statistically significant. 

Conclusion: In our experience, HSC assessment by ALDH activity yields the highest correlation with conventional analytical methods, particularly for post-thaw samples. Thus, this fast, inexpensive method has the potential to overcome the weaknesses of other techniques.

7. Effectiveness of Visual Methods in Information Procedures for Stem Cell Recipients and Donors
Çağla Sarıtürk, Çiğdem Gereklioğlu, Aslı Korur, Süheyl Asma, Mahmut Yeral, Soner Solmaz, Nurhilal Büyükkurt, Songül Tepebaşı, İlknur Kozanoğlu, Can Boğa, Hakan Özdoğu
doi: 10.4274/tjh.2016.0118  Pages 321 - 327
Objective: Obtaining informed consent from hematopoietic stem cell recipients and donors is a critical step in the transplantation process. Anxiety may affect their understanding of the provided information. However, use of audiovisual methods may facilitate understanding. In this prospective randomized study, we investigated the effectiveness of using an audiovisual method of providing information to patients and donors in combination with the standard model.
Materials and Methods: A 10-min informational animation was prepared for this purpose. In total, 82 participants were randomly assigned to two groups: group 1 received the additional audiovisual information and group 2 received standard information. A 20-item questionnaire was administered to participants at the end of the informational session.
Results: A reliability test and factor analysis showed that the questionnaire was reliable and valid. For all participants, the mean overall satisfaction score was 184.8±19.8 (maximum possible score of 200). However, for satisfaction with information about written informed consent, group 1 scored significantly higher than group 2 (p=0.039). Satisfaction level was not affected by age, education level, or differences between the physicians conducting the informative session.
Conclusion: This study shows that using audiovisual tools may contribute to a better understanding of the informed consent procedure and potential risks of stem cell transplantation.

8. Influence of L-Carnitine on Stored Rat Blood: A Study on Plasma
Carl Hsieh, Vani Rajashekharaiah
doi: 10.4274/tjh.2016.0343  Pages 328 - 333
Objective: Plasma acts as a good indicator of oxidative stress in blood. L-Carnitine is an antioxidant that reduces metabolic stress in cells, thereby providing a protective effect against oxidative stress (OS). L-Carnitine as an additive in storage has not been explored. Thus, this study attempts to analyze the role of L-carnitine in blood storage solution, citrate phosphate dextrose adenine (CPDA)-1, through OS markers including antioxidant enzymes, lipid peroxidation, and protein oxidation.
Materials and Methods: Blood was collected from male Wistar rats and stored in CPDA-1 solution with L-carnitine (10 mM, 30 mM, and 60 mM: groups LC 10, LC 30, and LC 60, respectively) and without L-carnitine (control group). Plasma was isolated every 5th day and the OS markers were analyzed.
Results: Superoxide dismutase (SOD) and sulfhydryl (SH) increased over storage in controls, LC 30, and LC 60. Catalase increased in LC 30 and LC 60 during storage. Thiobarbituric acid reactive substances (TBARS) and protein carbonyl (PrC) levels in all groups increased initially and reduced towards the end of storage. SOD and SH levels were maintained while TBARS and PrC levels increased in LC 10.
Conclusion: L-Carnitine was beneficial in terms of increased antioxidant capacity and SH and decreased lipid peroxidation. This forms the basis for further studies on L-carnitine as a constituent in storage solutions.

9. Antioxidants Attenuate Oxidative Stress-Induced Hidden Blood Loss in Rats
Hong Qian, Tao Yuan, Jian Tong, Wen Shuang Sun, Jiajia Jin, Wen Xiang Chen, Jia Meng, Nirong Bao, Jianning Zhao
doi: 10.4274/tjh.2016.0469  Pages 334 - 339
Objective: Hidden blood loss (HBL), commonly seen after total knee or hip arthroplasty, causes postoperative anemia even after reinfusion or blood transfusion based on the visible blood loss volume. Recent studies demonstrated that oxidative stress might be involved in HBL. However, whether the antioxidants proanthocyanidin (PA) or hydrogen water (HW) can ameliorate HBL remains poorly understood. The aim of this study was to evaluate the effects of PA and HW on HBL.
Materials and Methods: A rat HBL model was established through administration of linoleic acid with or without treatment with PA or HW. The levels of hemoglobin (Hb), red blood cell (RBC) count, superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-PX) activity, malondialdehyde (MDA), and ferryl Hb were measured.
Results: RBC and Hb values as well as the activity of SOD and GSHPX were reduced after administration of linoleic acid, which was ameliorated by treatment with PA or HW. In addition, the quantity of MDA was significantly decreased with the administration of PA or HW.
Conclusion: PA and HW could ameliorate HBL in a rat model by reducing oxidative stress, suggesting that they might be used as a novel therapeutic approach in the prophylaxis or treatment of HBL in clinics.

BRIEF REPORT
10. High Infection-Related Mortality in Pediatric Acute Myeloid Leukemia without Preventive Antibiotics and Antifungals: Retrospective Cohort Study of a Single Center from a Middle-Income Country
Emine Zengin, Nazan Sarper, Sema Aylan Gelen, Uğur Demirsoy, Meriban Karadoğan, Suar Çakı Kılıç, Selim Öncel, Emin Sami Arısoy, Devrim Dündar
doi: 10.4274/tjh.2017.0052  Pages 340 - 344
Objective: This study aimed to evaluate infection-related mortality in patients with acute myeloid leukemia (AML) treated without preventive antibiotics and antifungals in a middle-income country.
Materials and Methods: Infection-related mortality was evaluated retrospectively in 49 pediatric patients.
Results: A total of 173 chemotherapy courses were administered as first-line chemotherapy. Four patients died during induction: one patient due to intracranial bleeding, two patients due to typhlitis, and one patient due to invasive fungal infection with pulmonary vascular invasion and massive bleeding. Another two patients died with resistant disease. During consolidation there were four infectionrelated deaths and one death due to cardiotoxicity. In first-line chemotherapy mortality was 22% (11/49); infection-related mortality was 14% (7/49). Event-free survival and overall survival at 6 years were 42.9% and 61.2% (95% CI: 44-76 and 66-99 months), respectively.
Conclusion: Due to considerable infection-related deaths, antibacterial and mold-active antifungal prophylaxis may be tried during neutropenic periods in pediatric AML.

11. Hematopoietic Stem Cell Transplantation in Primary Immunodeficiency Patients in the Black Sea Region of Turkey
Alişan Yıldıran, Mehmet Halil Çeliksoy, Stephan Borte, Şükrü Nail Güner, Murat Elli, Tunç Fışgın, Emel Özyürek, Recep Sancak, Gönül Oğur
doi: 10.4274/tjh.2016.0477  Pages 345 - 349
Hematopoietic stem cell transplantation is a promising curative therapy for many combined primary immunodeficiencies and phagocytic disorders. We retrospectively reviewed pediatric cases of patients diagnosed with primary immunodeficiencies and scheduled for hematopoietic stem cell transplantation. We identified 22 patients (median age, 6 months; age range, 1 month to 10 years) with various diagnoses who received hematopoietic stem cell transplantation. The patient diagnoses included severe combined immunodeficiency (n=11), Chediak-Higashi syndrome (n=2), leukocyte adhesion deficiency (n=2), MHC class 2 deficiency (n=2), chronic granulomatous syndrome (n=2), hemophagocytic lymphohistiocytosis (n=1), Wiskott-Aldrich syndrome (n=1), and Omenn syndrome (n=1). Of the 22 patients, 7 received human leukocyte antigen-matched related hematopoietic stem cell transplantation, 12 received haploidentical hematopoietic stem cell transplantation, and 2 received matched unrelated hematopoietic stem cell transplantation. The results showed that 5 patients had graft failure. Fourteen patients survived, yielding an overall survival rate of 67%. Screening newborn infants for primary immunodeficiency diseases may result in timely administration of hematopoietic stem cell transplantation.

IMAGES IN HEMATOLOGY
12. Bullous Pyoderma Gangrenosum in a Patient with Acute Myelogenous Leukemia as a Pathergic Reaction after Bone Marrow Biopsy
Nur Efe İris, Reyhan Diz Küçükkaya, Mutlu Arat, Zahide Eriş
doi: 10.4274/tjh.2016.0096  Pages 350 - 351
Abstract |Full Text PDF

13. Giant Intracranial Solitary Plasmacytoma
Osman Kara, Tayfur Toptaş, Işık Atagündüz, Süheyla Bozkurt, Önder Şirikçi, Tülin Fıratlı Tuğlular
doi: 10.4274/tjh.2016.0199  Pages 352 - 353
Abstract |Full Text PDF

14. Peculiar Cold-Induced Leukoagglutination in Mycoplasma pneumoniae Pneumonia
Yasushi Kubota, Yuka Hirakawa, Kazuo Wakayama, Shinya Kimura
doi: 10.4274/tjh.2017.0203  Pages 354 - 355
Abstract |Full Text PDF

LETTER TO EDITOR
15. Liver Transplantation in a Patient with Acquired Dysfibrinogenemia Who Presented with Subdural Hematoma: A Case Report
Şencan Acar, Gökhan Güngör, Murat Dayangaç, Reyhan Diz Küçükkaya, Yaman Tokat, Murat Akyıldız
doi: 10.4274/tjh.2017.0045  Pages 356 - 357
Abstract |Full Text PDF

16. Chronic Active Parietal Osteomyelitis Due to Salmonella typhi in a Patient with Sickle Cell Anemia
Ahmad Antar, George Karam, Maurice Kfoury, Nadim El- Majzoub
doi: 10.4274/tjh.2017.0094  Pages 358 - 359
Abstract |Full Text PDF

17. Acquired Leukocyte Inclusion Bodies Resembling Döhle Bodies During Acute Cholangitis
Gökhan Özgür, Musa Barış Aykan, Murat Yıldırım, Selim Sayın, Ahmet Uygun, Cengiz Beyan
doi: 10.4274/tjh.2017.0121  Pages 359 - 360
Abstract |Full Text PDF

18. Three Novel Calreticulin Mutations in Two Turkish Patients
Veysel Sabri Hançer, Hüseyin Tokgöz, Serkan Güvenç, Ümran Çalışkan, Murat Büyükdoğan
doi: 10.4274/tjh.2017.0146  Pages 360 - 361
Abstract |Full Text PDF

19. Imatinib-Induced Interstitial Pneumonitis Successfully Switched to Nilotinib in a Patient with Prior History of Mycobacterium tuberculosis Infection
Zhuan - Bo Luo, Ning Xu, Xiao - Ping Huang, Guifang Ouyang
doi: 10.4274/tjh.2017.0155  Pages 362 - 364
Abstract |Full Text PDF

20. Prostate Involvement in a Patient with Follicular Lymphoma
Seda Yılmaz, Sinan Demircioğlu, Özlen Bektaş, Özcan Çeneli, Sıdıka Fındık
doi: 10.4274/tjh.2017.0181  Pages 364 - 365
Abstract |Full Text PDF

21. Coexistence of EZH2, NOTCH1, IL7R, and PHF6 Mutations in Adult T-cell Acute Lymphoblastic Leukemia
Xilian Zhou, Yan Gu, Qi Han, Mario Soliman, Chunhua Song, Zheng Ge
doi: 10.4274/tjh.2017.0194  Pages 366 - 368
Abstract |Full Text PDF

22. Circulating Tumor Cells in Neuroblastoma
Mili Jain, Ashutosh Kumar, Sanjay Mishra, Nishant Verma, Madhu Mati Goel
doi: 10.4274/tjh.2017.0199  Pages 369 - 370
Abstract |Full Text PDF

23. Megakaryocytic Emperipolesis Associated with Thrombocytopenia: Causative or Coincidence?
Manu Goyal, Sreeja Thandilath Thekkelakayil, Anurag Gupta
doi: 10.4274/tjh.2017.0211  Pages 370 - 371
Abstract |Full Text PDF

24. First Observation of Hemoglobin San Diego, a High Oxygen Affinity Hemoglobin Variant, in Turkey
Ebru Yılmaz Keskin, Ali Fettah, Ana Catarina Oliveira, Şule Toprak, Andreia Lopes, Celeste Bento
doi: 10.4274/tjh.2017.0213  Pages 372 - 373
Abstract |Full Text PDF

25. A Case of Para-Bombay Phenotype Caused by Homozygous Mutation of the FUT1 Gene
Yu Jung - Kuang, Liu Yi - Hong, Er Tze - Kiong
doi: 10.4274/tjh.2017.0220  Pages 374 - 375
Abstract |Full Text PDF

26. A Myopathy, Lactic Acidosis, Sideroblastic Anemia (MLASA) Case Due to a Novel PUS1 Mutation
Çiğdem Seher Kasapkara, Leyla Tümer, Nadia Zanetti, Fatih Ezgü, Eleonora Lamantea, Massimo Zeviani
doi: 10.4274/tjh.2017.0231  Pages 376 - 377
Abstract |Full Text PDF

27. Frequency and Risk Factors for Secondary Malignancies in Patients with Mycosis Fungoides
Fatma Pelin Cengiz, Nazan Emiroğlu, Nahide Onsun
doi: 10.4274/tjh.2017.0234  Pages 378 - 379
Abstract |Full Text PDF

28. Leishmaniasis: Bone Marrow Aspirate Smear and Rapid Antibody Test
Beuy Joob, Viroj Wiwanitkit
doi: 10.4274/tjh.2017.0291  Page 380
Abstract |Full Text PDF

29. Receiver operating characteristic curve analysis may be helpful to study the prognostic value of miR-155 in B cell non-hodgkin lymphoma
Long Su
doi: 10.4274/tjh.2017.0297  Page 381
Abstract |Full Text PDF

NONE
30. Author Index 2017

Pages E1 - E3
Abstract |Full Text PDF

31. Subject Index 2017

Pages E4 - E12
Abstract |Full Text PDF