E-ISSN: 1308-5263
Turkish Journal of Hematology - Turk J Hematol: 37 (1)
Volume: 37  Issue: 1 - 2020
REVIEW
1. Acute Graft-Versus-Host Disease: A Brief Review
Elifcan Aladağ, Engin Kelkitli, Hakan Göker
doi: 10.4274/tjh.galenos.2019.2019.0157  Pages 1 - 4
Graft‐versus‐host disease (GvHD) is an important complication that can be observed after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Acute GvHD (aGvHD) is seen after alloHSCT and the incidence of aGvHD is around 30%-50%. aGvHD prophylaxis is essential in patients undergoing allo-HSCT. Initial therapy for aGvHD is steroids. Prognosis is poor in aGvHD patients not responding to steroids. In this article, the pathobiology, clinical findings, prophylaxis, and treatment of aGvHD will be summarized.

RESEARCH ARTICLE
2. Therapeutic Potentials of Inhibition of Jumonji C Domaincontaining Demethylases in Acute Myeloid Leukemia
Duygu Koca, Nurcan Haştar, Selin Engür, Yağmur Kiraz, Gizem Tuğçe Ulu, Demet Çekdemir, Yusuf Baran
doi: 10.4274/tjh.galenos.2019.2019.0083  Pages 5 - 12
Objective: Acute myeloid leukemia (AML) is a complex disease affected by both genetic and epigenetic factors. Histone methylation and demethylation are types of epigenetic modification in chromatin remodeling and gene expression. Abnormal expression of histone demethylases is indicated in many types of cancer including AML. Although many commercial drugs are available to treat AML, an absolute cure has not been discovered yet. However, inhibition of demethylases could be a potential cure for AML. Methylstat is a chemical agent that inhibits the Jumonji C domain-containing demethylases.
Materials and Methods: The cytotoxic and apoptotic effects of methylstat and doxorubicin on HL-60 cells were detected by MTT cell viability assay, double staining of treated cells with annexin-V/ propidium iodide, and caspase-3 activity assay. Mitochondrial activity was analyzed using JC-1 dye. The expression levels of the BCL2 and BCL2L1 anti-apoptotic genes in HL-60 cells were determined using real-time polymerase chain reaction (PCR). Lastly, the cytostatic effect was determined by cell cycle analysis.
Results: In our research, cytotoxic, cytostatic, and apoptotic effects of methylstat on human HL-60 cells were investigated. Cytotoxic and cytostatic analyses revealed that methylstat decreased cell proliferation in a dose-dependent cytotoxic manner and arrested HL60 cells in the G2/M and S phases. Methylstat also induced apoptosis through the loss of mitochondrial membrane potential and increases in caspase-3 enzyme activity. The expression levels of BCL2 and BCL2L1 were also decreased according to real-time PCR results. Finally, the combination of methylstat with doxorubicin resulted in synergistic cytotoxic effects on HL-60 cells.
Conclusion: Taken together, these results demonstrate that methylstat may be a powerful candidate as a drug component of AML treatment protocols.

3. Effects of the Proteasome Inhibitor Bortezomib in Combination with Chemotherapy for the Treatment of Mantle Cell Lymphoma: A Meta-analysis
Shi-jun Li, Jian Hao, Yu Mao, Yu-ling Si
doi: 10.4274/tjh.galenos.2019.2019.0128  Pages 13 - 19
Objective: The efficacy and the safety of bortezomib-based chemotherapy were characterized in mantle cell lymphoma (MCL) patients.
Materials and Methods: The PubMed, Cochrane Library, Clinical Key, Science Direct, Oxford Journals, and China National Knowledge Internet databases were searched up to 1 May 2019. The selected trials needed to match the inclusion criteria and be carried out to evaluate quality appraisal and the synthesis of efficacy and safety. The enrolled MCL patients using bortezomib-based chemotherapy or chemotherapy alone needed to have been compared. The overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were combined to evaluate the efficacy while serious adverse events (SAEs) (grade III-IV peripheral neuropathy, neutropenia, and infection) were used to evaluate the safety. The heterogeneity of the results were analyzed simultaneously
Results: A total of 620 patients were enrolled across four studies in our meta-analysis, and the pooled results showed that the PFS [hazard ratio (HR)=0.66, 95% confidence interval (CI)=0.54-0.82; p=0.0001)] and OS (HR=0.73, 95% CI=0.55-0.96; p=0.03) of patients with bortezomib-based chemotherapy were better than those of patients with chemotherapy alone, unlike ORR (risk ratio=1.46, 95% CI=0.852.49; p=0.17), while SAEs were prominent in the combination group.
Conclusion: MCL patients who are ineligible for transplant or high-dose chemotherapy could benefit from bortezomib-based chemotherapy.

4. Predictive Values of Early Suppression of Tumorigenicity 2 for Acute GVHD and Transplant-related Complications after Allogeneic Stem Cell Transplantation: Prospective Observational Study
Ayako Matsumura, Takuya Miyazaki, Takayoshi Tachibana, Taiki Ando, Megumi Koyama, Satoshi Koyama, Yoshimi Ishii, Hiroyuki Takahashi, Yuki Nakajima, Ayumi Numata, Wataru Yamamoto, Kenji Motohashi, Maki Hagihara, Kenji Matsumoto, Shin Fujisawa, Hideaki Nakajima
doi: 10.4274/tjh.galenos.2019.2019.0139  Pages 20 - 29
Objective: A soluble form of suppression of tumorigenicity 2 (sST2) has emerged as a biomarker for acute graft-versus-host disease (GVHD) and non-relapse mortality (NRM). We prospectively monitored sST2 levels during the early phase of hematopoietic stem cell transplantation (HSCT) and evaluated the clinical association with transplant-related complications including acute GVHD.
Materials and Methods: Thirty-two adult Japanese patients who received a first allogeneic HSCT were enrolled in this study. Levels of sST2 were measured at fixed time points (pre-conditioning, day 0, day 14, day 21, and day 28).
Results: The median age was 50.5 years (range=16-66). With a median follow-up of 21.5 months (range=0.9-35.4), 9 patients developed grade II-IV acute GVHD. Median sST2 levels on the day of HSCT were higher than baseline and reached the maximum value (92.7 ng/mL; range=0-419.7) on day 21 after HSCT. The optimal cutoff value of sST2 on day 14 for predicting grade II-IV acute GVHD was determined as 100 ng/mL by ROC analysis. The cumulative incidence of acute GVHD was 56.7% and 16.5% in the high- and low-sST2 groups, respectively (p<0.01). Multivariate analyses showed that high sST2 levels at day 14 were associated with a higher incidence of acute GVHD (hazard ratio=9.35, 95% confidence interval=2.92-30.0, p<0.01). The cumulative incidence of NRM was increased in the highsST2 group (33% vs 0%, p<0.01), but all the patients died of non-GVHD complications. Among 6 patients in the high-sST2 group without grade II-IV GVHD, 5 patients developed veno-occlusive disease (VOD) and one also had thrombotic microangiopathy (TMA).
Conclusion: The early assessment of sST2 after HSCT yielded predictive values for the onset of acute GVHD and other transplant-related complications including VOD and TMA.

5. First-time Blood Donors Are Double-edged Swords for Blood Transfusion Centers: A Retrospective Study in Southwest Iran
Hamid Reza Niazkar, Akbar Dorgalaleh, Fariba Rad
doi: 10.4274/tjh.galenos.2019.2019.0166  Pages 30 - 35
Objective: First-time blood donors are the most common group of blood donors. They usually have different motivations for blood donation, some of which provoke the donors to hide risk factors of transfusion-transmissible infections (TTIs). Therefore, detection of TTIs among first-time donors is crucial and can decrease the rate of TTIs among blood recipients. This study aimed to evaluate the prevalence of TTIs among first-time donors in the transfusion center of Kohgiluyeh and Boyer-Ahmad Province (KBTC), Iran.
Materials and Methods: This retrospective study was conducted with volunteer blood donors in 2004-2014 in the KBTC. Various data, including sex, confidential unit exclusion (CUE), previous donation history, and the laboratory findings of confirmatory tests, were extracted from blood donor software. Data were analyzed by SPSS using the chi-square test.
Results: Among 198,501 blood donors, 52,527 (26.46%) were firsttime donors, while 145,974 donors (73.54%) were repeat and regular donors. Most of the donors (94.5%) were male, while a minority (5.5%) were female. The CUE option was chosen by 2,237 (1.13%) donors. The incidence of hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) was 247 (0.13%) and 134 (0.07%) among the entire study population, respectively. Three donors (0.002%) had confirmed human immunodeficiency virus (HIV), while none of the blood donors were positive for syphilis. Most of the donors with positive HBsAg (95.8%), HCV (86.6%), and HIV (100%) infection were first-time donors.
Conclusion: Since TTIs are more common among first-time blood donors than regular and repeat donors, special considerations should be taken into account for this common group of blood donors.

6. Percentages of CD4+CD8+ Double-positive T Lymphocytes in the Peripheral Blood of Adults from a Blood Bank in Bogotá, Colombia
Miguel S. Gonzalez-Mancera, Natalia Inés Bolaños Cristancho, Manuel Salamanca, Guillermo Orjuela, Ayda Nubia Rodríguez, John M. Gonzalez
doi: 10.4274/tjh.galenos.2019.2019.0256  Pages 36 - 41
Objective: CD4+CD8+ double-positive T-cells (DPTs) have been classified as a separate T-cell subpopulation, with two main phenotypes: CD4high CD8low and CD4low CD8high. In recent years, the relevance of DPTs in the pathogenesis of infections, tumors, and autoimmune diseases has been recognized. Reference values among healthy individuals remain unknown. Therefore, the aim of this study is to provide a reference value for DPTs in peripheral blood from healthy donors in a blood bank in Bogotá, Colombia, and to determine the activation status using a surface marker.
Materials and Methods: One hundred healthy donors were enrolled in the study. Peripheral blood cells were stained for CD3, CD4, CD8, and CD154 (CD40L), and cellular viability was assessed with 7-aminoactinomycin D and analyzed by flow cytometry.
Results: The median value for DPTs was 2.6% (interquartile range=1.70%-3.67%). Women had higher percentages of DPTs than men (3.3% vs. 2.1%). The subpopulation of CD4low CD8high showed higher expression of CD154 than the other T-cell subpopulations.
Conclusion: DPT reference values were obtained from blood bank donors. A sex difference was found, and the CD4low CD8high subpopulation had the highest activation marker expression.

PERSPECTIVES IN HEMATOLOGY
7. WHO 2016 Definition of Chronic Myeloid Leukemia and Tyrosine Kinase Inhibitors
İbrahim C. Haznedaroğlu, Işınsu Kuzu, Osman İlhan
doi: 10.4274/tjh.galenos.2019.2019.0241  Pages 42 - 47
Philadelphia (Ph*)/BCR-ABL1-positive chronic myeloid leukemia (CML) is considered as a chronic life-long disease, which could be manageable with tyrosine kinase inhibitor (TKI) drugs. The aim of TKI drug treatment is to provide age- and sex-matched duration of life in a given patient with CML. Personalized CML treatment with TKI drugs is the key strategy. Individual treatment approach includes the harmonization of CML disease characteristics, clinical experience, and best available clinical evidence. Specific CML disease characteristics in a given patient include; CML disease risk, comorbidities, molecular profile, compliance, lifestyle, and drug off-target risk profile. CML research evidence includes; randomized clinical trials indicating the data on the efficacy, safety, tolerability, toxicity, possible longterm adverse events, and pharmacoeconomy of TKIs. Clinical and physician experience includes TKI availability, TKI reimbursability, drug experience, adherence, and BCR-ABL1 monitorization facilities. The key decision of choosing a TKI of choosing TKIs for CML should be made via the consideration of these variables. The aim of this paper is to outline the latest 2016 World Health Organization definition of CML and its proper management with TKI-class drugs.

BRIEF REPORT
8. Blastic Plasmacytoid Dendritic Cell Neoplasia: A Single Center Experience
Ahu Senem Demiröz, Cuyan Demirkesen, Ayşe Salihoğlu, Nükhet Tüzüner
doi: 10.4274/tjh.galenos.2019.2019.0195  Pages 48 - 52
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare malignancy with skin tropism. The entity was recently defined and the diagnosis is generally made by skin biopsies. It is necessary to apply appropriate immunohistochemistry to recognize this rare entity. There is no consensus on therapy and the survival rates are low. The aim of this study is to describe the clinical and histopathological features of BPDCN. We retrospectively reviewed 8 BPDCN cases of the Cerrahpaşa Medical Faculty diagnosed between 2005 and 2019. We documented the clinical findings, histopathologic diagnoses, and outcomes. The mean age of the patients was 58.7 years (range=11-86 years), and 7 patients were male. The patients presented with erythematous or purple papules, plaques, and papulonodular or nodular cutaneous lesions. Two had lymphadenomegaly at presentation. In microscopic evaluations, tumor cells infiltrated the entire dermis with a clear-cut subepidermal Grenz zone in all cases. CD4, CD56, and CD123 were the most frequently expressed immunohistochemical markers. The median follow-up of 7 cases was 14 months, ranging from 6 to 48 months. Three patients died of the disease, while 4 patients were still alive. Out of 7 patients, 5 received chemotherapy. We found that the outcomes of some patients were different from others but we did not link any distinct clinical or histopathological characteristics to these different outcomes.

IMAGES IN HEMATOLOGY
9. Kasabach-Merritt Syndrome in an Adult
Milan Pantelic, Masa Pantelic, Petar Djuric, Katarina Markovic, Tamara Vucinic, Jovan Todor Juloski
doi: 10.4274/tjh.galenos.2019.2019.0068  Pages 53 - 54
Abstract |Full Text PDF

10. Platelet Satellitism
N. Yasemin Ardıçoğlu Akışın, Nejat Akar
doi: 10.4274/tjh.galenos.2019.2019.0171  Pages 55 - 56
Abstract |Full Text PDF

LETTER TO EDITOR
11. Assessment of Patients with von Willebrand Disease with ISTH/ BAT and PBQ Scores
Fatma Burcu Belen Apak, Elif Ümit Gülsüm Ümit, Yağmur Zengin, Melike Sezgin Evim, Ekrem Ünal, Hasan Mücahit Özbaş, Can Acıpayam
doi: 10.4274/tjh.galenos.2019.2019.0446  Pages 57 - 58
Abstract |Full Text PDF

12. Children with Iron Deficiency Anemia Have a Tendency to Hypercoagulation: An Evaluation by Thromboelastography
Ceren Kılcı, Lale Olcay, Beril Özdemir, Ali Fettah, Meriç Yavuz Çolak
doi: 10.4274/tjh.galenos.2019.2019.0027  Pages 59 - 62
Abstract |Full Text PDF

13. Successful Hemostasis with Extended Half-life Recombinant Factor VIII in Circumcision
Başak Koç, Metin İshak Öztürk, Bülent Zülfikar
doi: 10.4274/tjh.galenos.2019.2019.0305  Pages 62 - 63
Abstract |Full Text PDF

14. Accidental High-dose Intrathecal Treatment: Late Results of a Patient
Tiraje Celkan, Evrim Çifçi Sunamak
doi: 10.4274/tjh.galenos.2019.2019.0283  Pages 64 - 65
Abstract |Full Text PDF

15. CMV-specific T-Cells for Treatment of CMV Infection after Hematopoietic Stem Cell Transplantation in a Pediatric Case: First Application in Turkey
Sevil Celilova, Ersin Toret, Başak Adaklı Aksoy, Ercüment Ovalı, Ceyhun Bozkurt
doi: 10.4274/tjh.galenos.2019.2019.0293  Pages 65 - 67
Abstract |Full Text PDF

16. Comparison of Different Culture Conditions for Mesenchymal Stem Cells from Human Umbilical Cord Wharton’s Jelly for Stem Cell Therapy
Yu Bao, Shumin Huang, Zhengyan Zhao
doi: 10.4274/tjh.galenos.2019.2019.0439  Pages 67 - 69
Abstract |Full Text PDF

17. Vacuolated Blasts in the Bone Marrow of a Child with Rhabdomyosarcoma
Eda Ataseven, Dilek Ece, Nazan Özsan, Mehmet Kantar
doi: 10.4274/tjh.galenos.2019.2019.0324  Pages 70 - 71
Abstract |Full Text PDF

18. T-Cell Lymphoblastic Lymphoma Showing Aberrant Synaptophysin Expression in a Child
Nazım Emrah Koçer, Bermal Hasbay, Fazilet Kayaselçuk
doi: 10.4274/tjh.galenos.2019.2019.0307  Pages 72 - 73
Abstract |Full Text PDF

19. Hydroxyurea-induced Tooth Discoloration
Muhammed Okuyucu, Memiş Hilmi Atay
doi: 10.4274/tjh.galenos.2019.2019.0275  Pages 74 - 75
Abstract |Full Text PDF

20. Rare Presentation of Herpes Virus Lesions in a Case of Acute Pre-B Lymphoblastic Leukemia
Eylem Şerife Kalkan, Zeliha Güzelküçük, Melek Işık, Neşe Yaralı
doi: 10.4274/tjh.galenos.2018.2018.0372  Pages 75 - 76
Abstract |Full Text PDF