E-ISSN: 1308-5263
Turkish Journal of Hematology - Turk J Hematol: 30 (3)
Volume: 30  Issue: 3 - 2013
OBITUARY
1. Professor Antonio Cao: A Remembrance
Nejat Akar
Page 233
Abstract |Full Text PDF

REVIEW
2. Quality of Life and Supportive Care in Multiple Myeloma
Melda Cömert, Ajda Ersoy Güneş, Fahri Şahin, Güray Saydam
doi: 10.4274/Tjh.2012.0192  Pages 234 - 246
Multiple myeloma is the second most common haematological malignancy. Novel therapies have led to improvement in survival. Current myeloma management is matching the progress made in improved survival through disease control while optimising quality of life with effective supportive care. Supportive treatment is an essential part of the therapeutic management of myeloma patients because it is directed towards improving the patient’s quality of life and also can improve survival. The aim of this review is to highlight the relationship among life of quality, supportive care, and improvement in survival.

COMMENTARY
3. Current Management of Chronic Myeloid Leukemia with Tyrosine Kinase Inhibitors
İbrahim C. Haznedaroğlu
doi: 10.4274/Tjh.2013.0108  Pages 247 - 255
The clinical outcomes and survival of tyrosine kinase inhibitor (TKI)-treated patients with chronic myeloid leukemia (CML) have been significantly improved. The aim of this editorial is to outline critical steps of TKI administration practices during the long-term clinical course of CML based on data obtained from randomized clinical trials and international recommendations. The efficacy of TKI treatment, TKI side effects, off-target complications, and long-term morbidities due to both the disease and the drug are common arguments in the management of CML. Complete hematological response, early complete cytogenetic response, faster major molecular response, and deeper, more durable molecular responses (MR4, MR4.5, MR5) are the ultimate goals for TKI-receiving patients with CML.

ORIGINAL ARTICLE
4. Immunosuppressive Effects of Multipotent Mesenchymal Stromal Cells on Graft-Versus-Host Disease in Rats Following Allogeneic Bone Marrow Transplantation
Oral Nevruz, Ferit Avcu, A. Uğur Ural, Aysel Pekel, Bahar Dirican, Mükerrem Safalı, Elvin Akdağ, Murat Beyzadeoğlu, Tayfun İde, Ali Sengül
doi: 10.4274/Tjh.2013.0032  Pages 256 - 262
Objective: Graft-versus-host disease (GVHD) is a major obstacle to successful allogeneic bone marrow transplantation (allo-BMT). While multipotent mesenchymal stromal cells (MSCs) demonstrate alloresponse in vitro and in vivo, they also have clinical applications toward prevention or treatment of GVHD. The aim of this study was to investigate the ability of MSCs to prevent or treat GVHD in a rat BMT model.

Materials and Methods: The GVHD model was established by transplantation of Sprague Dawley rats’ bone marrow and spleen cells into lethally irradiated (950 cGy) SDxWistar rat recipients. A total of 49 rats were randomly assigned to 4 study and 3 control groups administered different GVHD prophylactic regimens including MSCs. After transplantation, clinical GVHD scores and survival status were monitored.

Results: All irradiated and untreated control mice with GVHD died. MSCs inhibited lethal GVHD as efficiently as the standard GVHD prophylactic regimen. The gross and histopathological findings of GVHD and the ratio of CD4/CD8 expression decreased. The subgroup given MSCs displayed higher in vivo proportions of CD25+ T cells and plasma interleukin-2 levels as compared to conventional GVHD treatment after allo-BMT.

Conclusion: Our results suggest that clinical use of MSCs in both prophylaxis against and treatment of established GVHD is effective. This study supports the use of MSCs in the prophylaxis and treatment of GVHD after allo-BMT; however, large scale studies are needed.

5. Regulation of Tumor Necrosis Factor-related Apoptosis-inducing Ligand Expression in Primary Acute Leukemic Cells by Chemotherapeutics
Shengmei Chen, Yanfang Liu, Hui Sun, Ling Sun, Jie Ma, Dingming Wan, Zhongxing Jiang, Qiutang Zhang, Tao Li
doi: 10.4274/Tjh.2013.0027  Pages 263 - 268
Objective: The expression of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein and its regulation by chemotherapeutics were analyzed in primary acute leukemic cells.

Materials and Methods: Peripheral blood was collected from 16 patients with acute leukemia on days 0, 1, 3, and 5 of chemotherapy. The mononuclear cells were separated from the peripheral blood, and TRAIL expression was assessed by flow cytometry. The bone marrow mononuclear cells of patients with acute leukemia were separated before chemotherapy and cultured in vitro with VP-16 and/or interferon (IFN). The TRAIL expression level was detected after the cell culture.

Results: TRAIL expression in the mononuclear cells of peripheral blood was significantly upregulated on day 1 (p<0.05) and then significantly decreased on day 5 after chemotherapy (p<0.05). Results from the in vitro culture revealed that VP-16 upregulated TRAIL expression in the bone marrow mononuclear cells of patients with acute leukemia, but the binding of VP-16 to IFN did not enhance TRAIL expression as compared with VP-16 alone (p>0.05).

Conclusion: OA single chemotherapy mechanism for leukemia may suffice to induce TRAIL expression and promote the apoptosis of leukemic cells.

6. Knowledge, Attitudes, and Practices of Hematologists Regarding Fertility Preservation in Turkey
Mert Küçük, İrfan Yavaşoğlu, Ali Zahit Bolaman, Gürhan Kadıköylü
doi: 10.4274/Tjh.2012.0015  Pages 269 - 274
Objective: Fertility preservation stands before us as an issue of quality of life for cancer patients and their partners and families. Therefore, the object of the present study was to determine the extent of the knowledge that hematologists have about fertility preservation and to understand their attitudes and practices regarding this matter.

Materials and Methods: A total of 25 hematologists participated in a survey. The questionnaire included questions on sociodemographic characteristics and awareness concerning the subject of fertility preservation, as well as questions designed to determine the extent of the knowledge that hematologists had on the subject and to understand their attitudes and practices in this context.

Results: Of the participants in the study, all expressed their awareness of the adverse effects that the various treatments they were prescribing could have on fertility; 2 (8%) revealed that they had never heard of the concept of fertility preservation. Of the participants, 19 (76%) indicated that they did not have adequate knowledge about fertility preservation, but 22 (88%) fortunately expressed a need for acquiring more knowledge about the subject. Of the respondents, 23 (92%) said that they did not have any brochures or published resources on this subject and stated their belief that if hematologists did have such documents, they would have more opportunity to discuss the various fertility preservation options with patients. All of the participants in the survey supported the idea of the Turkish Society of Hematology publishing a guidebook on this subject and organizing a session on fertility preservation in their regular congress.

Conclusion: Meeting the needs of hematologists for training and knowledge in the subject of fertility preservation and ensuring the development of appropriate attitudes and practices in this area is an important issue. The Turkish Society of Hematology may play a significant key role.

7. Prognostic Significance of Bcl-2 and p53 Protein Expressions and Ki67 Proliferative Index in Diffuse Large B-cell Lymphoma
Betül Bolat Küçükzeybek, Sadi Bener, Aylin Orgen Çallı, Tuğba Doğruluk Paksoy, Bahriye Payzin
doi: 10.4274/Tjh.2011.0034  Pages 275 - 282
Objective: Diffuse large B-cell lymphoma (DLBCL) is a high-grade neoplasm that has heterogeneous properties in clinical, morphological, and immunophenotypic aspects. In the present study the effects of p53, Bcl-2, and Ki67 on prognosis and their relationships with clinical parameters were examined.

Materials and Methods: Thirty-five patients who had been diagnosed with nodally located DLBCL at İzmir Atatürk Training and Research Hospital between January 1999 and June 2006 were included in the study. The Ann Arbor classification system was used to determine the stage of the patients. The patients were evaluated according to age, sex, stage, B symptoms, extranodal involvement, and lactate dehydrogenase (LDH) level as well as immunohistochemically. P53 protein and Bcl-2 oncoprotein expressions and Ki67 proliferation index were assessed immunohistochemically.

Results: High Bcl-2 expression was found in 9 patients (25.7%), high p53 expression was found in 10 patients (28.6%), and high Ki67 was observed in 23 patients (65.7%). There was no significant correlation between p53 expression, Bcl-2 expression, or Ki67 proliferation index and age, sex, stage, B symptoms, extranodal involvement, LDH level, and overall survival (p>0.05). We did not find a relationship among p53 expression, Bcl-2 expression, Ki67 proliferation index, and prognosis (p>0.05). There was no significant relationship between overall survival and age, sex, stage, B symptoms, extranodal involvement, or LDH level (p>0.05). Our results revealed that Bcl-2 and p53 protein expressions and Ki67 proliferation index have no effect on overall survival of patients with DLBCL.

Conclusion: The prognostic importance of p53 and Bcl-2 protein expressions and Ki67 proliferation index in DLBCL, which has biological and clinical heterogeneity, can be understood in a large series of studies that have subclasses and immunohistochemical markers with optimal cut-off values.

8. Detection of Left Ventricular Regional Function in Asymptomatic Children with beta-Thalassemia Major by Longitudinal Strain and Strain Rate Imaging
Ali Bay, Osman Başpınar, Göksel Leblebisatan, Ali Seçkin Yalçın, Ahmet İrdem
doi: 10.4274/Tjh.2012.0065  Pages 283 - 289
Objective: Cardiac failure due to iron overload remains the most common cause of death in patients with beta-thalassemia major. This study aimed to evaluate myocardial function in children with beta-thalassemia major using standard echocardiography technique and strain rate imaging.

Materials and Methods: Conventional echocardiographic analysis, tissue velocity imaging, and strain/strain rate imaging of the left ventricle were evaluated in 48 children with beta thalassemia major (19 girls, 29 boys; 8.39±4.05 years) and 22 healthy children (11 girls, 11 boys; 8±3.72 years).

Results: Conventional echocardiographic examinations revealed that beta-thalassemia patients had larger left ventricular end-systolic diameter, end-diastolic and end-systolic volume, left ventricular mass index, and mitral early/late diastolic flow velocity ratio (p<0.05). Strain and strain rate imaging study of the basal lateral wall of the left ventricle was higher in patients than in controls, at p=0.035 and p=0.008, respectively.

Conclusion: We found that superior systolic strain and strain rate imaging of the left ventricle indicated the presence of regional systolic function in the left ventricular wall. We suggest that left ventricle volume and mass index parameters might be more sensitive than the other conventional and strain/strain rate imaging parameters during childhood. However, the adulthood strain and strain rate imaging values may be lower than controls, exceeding the critical level of iron overload.

9. Endocrinological and Cardiological Late Effects Among Survivors of Childhood Acute Lymphoblastic Leukemia
Hale Ören, Şebnem Yılmaz, Özlem Tüfekçi, Mustafa Kır, Ece Böber, Gülersu İrken, Pakize Karakaya
doi: 10.4274/Tjh.2012.0094  Pages 290 - 299
Objective: Survival rates for childhood acute lymphoblastic leukemia (ALL) have significantly improved and late effects of therapy have been important in the follow-up of survivors. The objective of this study is to identify the endocrinological and cardiological late effects of ALL patients treated in our pediatric hematology unit.

Materials and Methods: Patients treated for ALL with BFM protocols after at least 5 years of diagnosis and not relapsed were included in the study. Endocrinological late effects (growth failure, obesity, insulin resistance, dyslipidemia, thyroid gland disorders, osteopenia/osteoporosis, and pubertal disorders) and cardiological late effects were evaluated. The study group was evaluated with anthropometric measurements, body mass index, and laboratory testing of fasting glucose, insulin, serum lipids, thyroid functions, and bone mineral densities. Echocardiography and pulsed wave Doppler imaging were performed for analysis of cardiac functions.

Results: Of the 38 ALL survivors, at least 1 adverse event occurred in 23 (60%), with 8 of them (21%) having multiple problems. Six (16%) of the survivors were obese and 8 (21%) of them were overweight. Subjects who were overweight or obese at the time of diagnosis were more likely to be overweight or obese at last follow-up. Obesity was more frequently determined in patients who were younger than 6 years of age at the time of diagnosis. Insulin resistance was observed in 8 (21%) subjects. Insulin resistance was more frequently seen in subjects who had family history of type 2 diabetes mellitus. Hyperlipidemia was detected in 8 (21%) patients. Hypothyroidism or premature thelarche were detected in 2 children. Two survivors had osteopenia. Cardiovascular abnormalities occurred in one of the subjects with hypertension and cardiac diastolic dysfunction.

Conclusion: We point out the necessity of follow-up of these patients for endocrinological and cardiological late effects, since at least one adverse event occurred in most of our cases.

10. Significance of Neuropilin-1 Expression in Acute Myeloid Leukemia
Tarif H. Sallam, Manal A.shams Eldin El Telbany, Hanan M. Mahmoud, Mutea A. Iskander
doi: 10.4274/Tjh.2011.0005  Pages 300 - 306
Objective: Neuropilin-1 is a vascular endothelial growth factor receptor that acts as a mediator of angiogenesis. Its importance in hematological malignancies such as acute myeloid leukemia (AML) remains to be elucidated. The aim of this study was to evaluate the significance of neuropilin-1 expression in AML patients by both flow cytometry and real-time polymerase chain reaction (PCR) in regard to its diagnostic and prognostic values.

Materials and Methods: Bone marrow aspirates of 44 patients with de novo AML and 12 relapsed AML patients were examined in this study. Ten subjects with nonhematological malignancy serving as the control group were also included.

Results: Neuropilin-1 expression by flow cytometry showed a highly significant increase in de novo and relapsed AML patients with a mean of 27.1±17.5% and 21.5±16.6%, respectively, compared to control group’s mean of 3.4±1.9%. A cut-off value of 6% was established as differentiating patients from the control group. By real-time PCR, no statistical significance was found in de novo and relapsed AML patients with a mean of 1.9±3.6 IU/L and 0.3±0.2 IU/L, respectively, compared to the control group’s mean of 0.3±0.1 IU/L. Neuropilin-1 surface expression by flow cytometry showed a significant correlation with total leukocyte count and a negative correlation with hemoglobin level in de novo AML patients. In relapsed AML patients, positive significant correlations were found with age, bone marrow blast percentage, and CD14. Neuropilin-1 mRNA level by real-time PCR showed a positive significant correlation with peripheral blood blast percentage and CD117 and a negative correlation with hemoglobin level in de novo AML patients. In relapsed patients, a positive correlation was found with lactate dehydrogenase.

Conclusion: Neuropilin-1 can be used as a tool for diagnosis and prognosis in AML patients.

BRIEF REPORTS
11. Effects of Omeprazole on Iron Absorption: Preliminary Study
Mahmut Yaşar Çeliker, Anupama Chawla, Catherine Messina, Mila Tempel
doi: 10.4274/tjh.2013.0042  Pages 307 - 310
Objective: Increasing numbers of pediatric and adult patients are being treated with proton pump inhibitors (PPIs). PPIs are known to inhibit gastric acid secretion. Nonheme iron requires gastric acid for conversion to the ferrous form for absorption. Ninety percent of dietary and 100% of oral iron therapy is in the nonheme form. To the best of our knowledge, the effect of PPIs on iron absorption has not been studied in humans. Our study assessed the relationship between omeprazole therapy and iron absorption in healthy subjects.

Materials and Methods: We recruited 9 healthy volunteers between June 2010 and March 2011. Subjects with chronic illness, anemia, or use of PPI therapy were excluded. Serum iron concentrations were measured 1, 2, and 3 h after the ingestion of iron (control group). The measurements were repeated on a subsequent visit after 4 daily oral administrations of omeprazole at a dose of 40 mg (treatment group).

Results: One female and 8 male volunteers were enrolled in the study with a mean age of 33 years. There was no statistical difference detected between baseline, 1-h, 2-h, and 3-h iron levels between control and treatment groups.

Conclusion: Administration of omeprazole for a short duration does not affect absorption of orally administered iron in healthy individuals.

CASE REPORT
12. A Case of Hypereosinophilic Syndrome Presenting with Multiorgan Thromboses Associated with Intestinal Obstruction
Tao Sui, Qing Li, Li Geng, Xinnv Xu, Yuming Li
doi: 10.4274/Tjh.2012.0141  Pages 311 - 314
Idiopathic hypereosinophilic syndrome (HES) is a disease characterized by persistent hypereosinophilia (>1.5×109/L) for more than 6 months in the absence of other causes of reactive eosinophilia. Patients with HES presenting with multiorgan thromboses are rare. Herein we report a 57-year-old man with HES who presented with deep venous thrombosis of the lower extremities, portal thrombosis, pulmonary embolism, and mesenteric venous thrombosis, which led to intestinal obstruction.

13. Late Onset Epstein Barr Virus Seropositive Posttransplant Lymphoproliferative Disorder in Two Renal Transplant Receivers
Saime Paydaş, Semra Paydaş, Mustafa Balal, Arbil Açıkalın, Melek Ergin, Emel Gürkan, Fikri Başlamışlı
doi: 10.4274/Tjh.2012.0017  Pages 315 - 320
Posttransplant malignancy is one of the most important complications of organ transplantation. Immunosuppressive drugs, viral infections such as human herpes virus 8 or Epstein-Barr virus, exposure to carcinogenic factors such as sun, and host factors can be etiologic factors in the development of malignant disease. In this paper we report 2 cases of late posttransplant lymphoproliferative disorder with malign behavior.

14. Ecthyma Gangrenosum-like Lesions in a Febrile Neutropenic Patient with Simultaneous Pseudomonas Sepsis and Disseminated Fusariosis
Seven Uludokumacı, İlker İnanç Balkan, Bilgül Mete, Reşat Özaras, Neşe Saltoğlu, Teoman Soysal
doi: 10.4274/Tjh.2012.0030  Pages 321 - 324
Fusarium spp. is an opportunistic mold that causes disseminated infections in immunocompromised patients. It is important to make a definite diagnosis because of high mortality rates. We present the case of a 27-year-old pregnant woman diagnosed with acute myeloid leukemia with a prolonged febrile neutropenic period. She developed ecthyma gangrenosum-like lesions and simultaneously had Pseudomonas bacteremia and disseminated fusariosis. Histopathological and microbiological features of skin lesions had a critical role in differential diagnosis. Ecthyma gangrenosum-like lesions due to disseminated fusariosis might be easily misdiagnosed as lesions associated with Pseudomonas unless tissue cultures and histopathological examinations are performed.

15. A Neonatal Thrombosis Patient Treated Successfully with Recombinant Tissue Plasminogen Activator
Kemal Erdinç, Serdar Ümit Sarıcı, Orçun Dabak, Orhan Gürsel, Adem Güler, Ahmet Emin Kürekçi, Fuat Emre Canpolat
doi: 10.4274/Tjh.07641  Pages 325 - 327
Herein we report an asphyctic preterm neonate with respiratory distress and prothrombotic risk factors that responded positively to rtPA treatment following 2 attacks of acute thrombosis.

LETTER TO THE EDITOR
16. The Impact of Eltrombopag Administration on the Clinical Course of Severe Refractory Fatal Acquired Aplastic Anemia
Ayşe Işık, Eylem Eliaçık, İbrahim C. Haznedaroğlu, Salih Aksu, Nilgün Sayınalp, Yahya Büyükaşık, Hakan Göker, Osman Özcebe
doi: 10.4274/Tjh-2013.0005  Pages 328 - 330
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17. β-Thalassemia Mutation At Codon 37 (TGG>>TGA) Detected In A Turkish Family
Derya Güleç, Sibel Bilgili, Nuriye Uzuncan, Giray Bozkaya, Nur Soyer, Baysal Karaca
doi: 10.4274/Tjh-2013.0073  Pages 331 - 332
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18. Follicular Lymphoma Patient Relapsing with Paraneoplastic Sensory Neuronopathy (Ganglioneuropathy)
Kadir Öztürk, Hakan Akgün, Yusuf Emrah Eyi, Yakup Aksoy, Mustafa Çakar
doi: 10.4274/TJH-2013.0125  Pages 333 - 335
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19. Gynecomastia in a Boy with Chronic Myeloid Leukemia during Imatinib Therapy
Betül Tavil, Sibel Kınık, Ahmet Gözen, Lale Olcay
doi: 10.4274/TJH-2013-0109  Pages 336 - 337
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20. Is There an Optimal Timing of Autologous Stem-Cell Transplantation for Multiple Myeloma in the Era of Novel Agents?
Selami Koçak Toprak
doi: 10.4274/Tjh.2013.0079  Pages 338 - 339
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IMAGES IN HEMATOLOGY
21. Mees’ Lines in an Acute Myeloid Leukemia Patient
Soumaya Anoun, Meryem Qachouh, Mouna Lamchahab, Asmae Quessar, Said Benchekroun
doi: 10.4274/Tjh.2013.0048  Page 340
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22. The Side Effects of Imatinib
Elmas Uzer, Ali Ünal, M. Yavuz Köker, Suat Ali Doğan
doi: TJH-2011.0018  Page 341
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