E-ISSN: 1308-5263
Turkish Journal of Hematology - Turk J Hematol: 27 (2)
Volume: 27  Issue: 2 - 2010
REVIEW
1. Radiation Therapy For The Solitary Plasmacytoma
Esengül Koçak, Giorgio Ballerini, Abderrahim Zouhair, Mahmut Özşahin
doi: 10.5152/tjh.2010.01  Pages 57 - 61
Plasma-cell neoplasms are classically categorized into four groups as: multiple myeloma (MM), plasma-cell leukemias, solitary plasmacytomas (SP) of the bone (SPB), and extramedullary plasmacytomas (EMP). These tumors may be described as localized or diffuse in presentation. Localized plasma-cell neoplasms are rare, and include SP of the skeletal system, accounting for 2-5% of all plasma-cell neoplasms, and EMP of soft tissue, accounting for approximately 3% of all such neoplasms. SP is defined as a solitary mass of neoplastic plasma cells either in the bone marrow or in various soft tissue sites. There appears to be a continuum in which SP often progresses to MM. The main treatment modality for SP is radiation therapy (RT). However, there are no conclusive data in the literature on the optimal RT dose for SP. This review describes the interrelationship of plasma-cell neoplasms, and attempts to determine the minimal RT dose required to obtain local control.

RESEARCH ARTICLE
2. The protection of the myocardium by amifostine against mitoxantrone-induced acute cardiotoxicity in rats
Vefki Gürhan Kadıköylü, İbrahim Meteoğlu, Süleyman Demir, Hülya Aybek, Mete Kalak, Muharrem Balkaya, Çiğdem Yenisey, Zahit Bolaman
doi: 10.5152/tjh.2010.02  Pages 62 - 69
OBJECTIVE: Amifostine (AMI) has been used for the prevention of doxorubicin-induced cardiotoxicity in several experimental and a few clinical studies. The aim of this study was to investigate the effects of AMI on lipid peroxidation, protective enzymes, and mitoxantrone (MITO)-induced acute cardiotoxicity in the rat heart using biochemical tests and histopathological examinations.
METHODS: Thirty-six rats were divided into six groups (n=6 in each). Control rats were given intraperitoneal (i.p.) serum saline and AMI group rats were given 200 mg/kg AMI i.p. Rats received MITO-2.5 and 5 mg/kg i.p. in the MITO-2.5 and MITO-5 groups. AMI 200 mg/kg i.p. was administered 30 min. before the same doses of MITO in the MITO-2.5+AMI and MITO-5+AMI groups.
RESULTS: The levels of cardiac enzymes such as creatinine phosphokinase-myocardial band and cardiac troponin T did not change. Malondialdehyde (MDA) levels increased in MITO groups compared to controls. Catalase and glutathione (GSH) levels in the MITO and MITO+AMI groups were higher than in controls. Superoxide dismutase and glutathione peroxidase levels were not different between MITO groups and controls. There was no difference in MDA levels between MITO+AMI groups and controls. Calcium deposition was not detected. The scores of fibrosis, apoptosis, inflammation, and degeneration in MITO groups were higher than in controls. The scores of fibrosis, degeneration and inflammation in MITO+AMI groups were lower.
CONCLUSION: MITO caused lipid peroxidation and myocardial damage, and the myocardium increased catalase and GSH levels to prevent this damage. AMI can protect against MITO-induced acute cardiotoxicity, decreasing myocardial damage and lipid peroxidation.

3. Functional proteomic analysis of Ankaferd® Blood Stopper
Duygu Özel Demiralp, İbrahim C. Haznedaroglu, Nejat Akar
doi: 10.5152/tjh.2010.03  Pages 70 - 77
OBJECTIVE: Ankaferd® Blood Stopper (ABS) comprises a standardized mixture of the plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica. The basic mechanism of action for ABS is the formation of an encapsulated protein network that provides focal points for vital erythrocyte aggregation. ABS–induced protein network formation with blood cells, particularly erythrocytes, covers the primary and secondary hemostatic system without disturbing individual coagulation factors.
METHODS: To understand the effect mechanisms of ABS on hemostasis, a proteomic analysis using 2D gel electrophoresis and mass spectrometer was performed.
RESULTS: Proteins of plant origin in Ankaferd® were NADP-dependent-malic enzyme, ribulose bisphosphate-carboxylase-large chain, maturase K, ATP synthase subunit-beta, ATP synthase subunit-alpha, chalcone-flavanone isomerase-1, chalcone-flavanone isomerase-2, and actin-depolymerizing factor. Furthermore, functional proteomic studies revealed that proteins resembling human peptides have been detected within Ankaferd®, including ATP synthase, mucin-16 (CD164 sialomucin-like 2 protein), coiled-coil domain containing 141 hypothetical protein LOC283638 isoform 1, hypothetical protein LOC283638 isoform 2, dynactin 5, complex I intermediate-associated protein 30, mitochondrial, NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, TP synthase, H+ transporting, mitochondrial actin binding 1 isoform, LIM domain and actin binding 1 isoform a, LIM domain and actin binding 1 isoform b, spectrin alpha non erythrocytic 1, prolactin releasing hormone receptor, utrophin, tet oncogene family member 2 isoform b, protein phosphatase 1 regulatory subunit 12A, NIMA (never in mitosis gene a)-related kinase, ATP-binding cassette protein C12, Homo sapiens malic enzyme 1, mitochondrial NADP(+)-dependent malic enzyme 3, ME2 protein, nuclear factor 1 B-type, abhydrolase domain-containing protein 12B, E3 SUMO-protein ligase PIAS2, alpha-1, 2-glucosyltransferase ALG10-A, cofilin, non-muscle isoform, 18 kDa phosphoprotein, p18, actin-depolymerizing factor (ADF), twinfilin-1, ankyrin repeat and FYVE domain-containing protein 1, usherin precursor, urotensin II receptor, interleukin 4, and midkine.
CONCLUSION: Proteomic analysis of Ankaferd® represents a true basis for the upcoming Ankaferd® studies focusing on its wound healing, hemostatic, anti-infective, antineoplastic, and preservative biological actions.

4. Cytotoxic T lymphocyte antigen-4 (CTLA-4) A49G polymorphism and autoimmune blood diseases
Faruk Aktürk, Veysel Sabri Hançer, Reyhan Küçükkaya
doi: 10.5152/tjh.2010.04  Pages 78 - 81
OBJECTIVE: The cytotoxic T lymphocyte associated antigen-4 (CTLA-4) is expressed on T lymphocytes, and inhibits the T-cell responses. In animal models, it has been shown that complete CTLA-4 deficiency was lethal due to massive infiltration of tissues by polyclonally proliferating lymphocytes. CTLA-4 A49G polymorphism, which has been suggested to reduce the inhibitory function of the CTLA-4 molecule, was found to be associated with various autoimmune diseases in recent studies.
METHODS: In this study, we evaluated the frequency of CTLA-4 A49G polymorphism in 46 patients with autoimmune hemolytic anemia (AIHA), 62 patients with immune thrombocytopenic purpura (ITP), and 150 healthy individuals.
RESULTS: Allele frequencies and genotype distributions were similar in both ITP and AIHA patients compared to healthy individuals. In subgroup analysis, however, we found that in chronic lymphocytic leukemia (CLL) patients with AIHA (n=4), all patients had CTLA-4 A49G polymorphism (3 had AG, 1 had GG). There was no significant statistical association between G allele and systemic lupus erythematosus (SLE) or AIHA.
CONCLUSION: These data suggest that CTLA-4 A49G polymorphism does not contribute to the pathogenesis of lymphoproliferative diseases itself, nor does it increase the risk of autoimmune complications in patients with lymphoproliferative disease.

5. Enhanced platelet adhesion in essential thrombocythemia after in vitro activation
Andreas C. Eriksson, Kourosh Lotfi, Per A. Whiss
doi: 10.5152/tjh.2010.05  Pages 82 - 90
OBJECTIVE: Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by elevated platelet counts and increased risk of thrombosis. Ex vivo data suggest increased platelet reactivity in agreement with the increased thrombosis risk, while in vitro tests often detect decreased platelet activity. The present study aimed to investigate adhesion of ET-platelets in vitro, which is an aspect of platelet function that has been addressed in only a few studies on ET patients.
METHODS: The study included 30 ET patients and 14 healthy controls. Platelet adhesion was measured with a static platelet adhesion assay.
RESULTS: The main finding was that ET-platelets were more readily activated by adhesion-inducing stimuli in vitro than control platelets. This was particularly evident in elderly patients and when using multiple stimuli, such as surfaces of collagen or fibrinogen combined with addition of adenosine 5’-diphosphate or ristocetin. Such multiple stimuli resulted in adhesion above the control mean +2 standard deviations for approximately 50% of the patients.
CONCLUSION: The results are in accordance with the concept of increased platelet activity in ET, but opposite to most other in vitro studies. We suggest that the conditions in the adhesion assay might mimic the in vivo situation regarding the presence of chronic platelet activation.

6. Clinical Aspects Of Sclerodermatous Type Graft-Versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation
Hatice Şanlı, Bengü Nisa Akay, Ender Soydan, Pelin Koçyiğit, Mutlu Arat, Osman İlhan
doi: 10.5152/tjh.2010.06  Pages 91 - 98
OBJECTIVE: We aimed to evaluate the clinical features of sclerodermatous chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (AHSCT).
METHODS: We retrospectively analyzed 423 patients who underwent AHSCT. We assessed age, sex, pre-transplant diagnosis, conditioning regimen, GVHD prophylaxis, and occurrence of acute GVHD (aGVHD), chronic lichenoid and chronic systemic GVHD, and clinical properties of sclerodermatous GVHD.
RESULTS: Sclerotic skin lesions developed in 22 patients after a mean of 752±647 days (median 480). aGVHD appeared in 17 patients, with hepatic involvement in 2, gastrointestinal tract involvement in 2 and skin involvement in 13 of these patients. Extensive chronic GVHD (liver, pulmonary, skin and oral mucosa) developed in 12 patients. Sclerosis was generalized in 19 patients (86.4%) and localized in 3 patients (13.6%). Leopard skin eruption appeared in 8 (36.4%) of the 19 patients with generalized sclerodermatous changes. In most cases, sclerotic lesions appeared on the trunk, and distal parts of the extremities were spared. Eight patients (36.4%) progressed from lichenoid to sclerodermatous lesions, 2 (9.1%) with lichenoid and sclerodermatous phases together and 12 (55.5%) with de novo sclerodermatous lesions. Five patients died because of late transplant-related complications.
CONCLUSION: Sclerodermatous GVHD has a late onset and may be quite disabling. Unlike scleroderma, acral involvement is seen rarely. Although most lesions do not disappear in the course of the disease, most patients have a good prognosis.

7. New in vitro effects of clopidogrel on platelets in hyperlipidemic and healthy subjects
Derya Özsavcı, Azize Şener, Rabia Oba, Gülderen Yanıkkaya Demirel, Fikriye Uras, Turay Kevser Yardımcı
doi: 10.5152/tjh.2010.07  Pages 99 - 108
OBJECTIVE: We aimed to detect novel in vitro effects of clopidogrel on platelets by assessment of the following parameters: malondialdehyde, glutathione, nitrite, aggregation response, and expressions of P-selectin, fibrinogen, apolipoprotein A1, apolipoprotein B, and phosphatidylserine.
METHODS: Platelets were obtained from healthy (n: 9) and hyperlipidemic (n: 9) volunteers. Expressions of P-selectin, fibrinogen, apolipoproteins A1/B and phosphatidylserine with and without clopidogrel were assayed by flow cytometry. Malondialdehyde, glutathione, aggregation and nitrite levels were also assayed.
RESULTS: Without clopidogrel, the baseline values of platelet aggregation, malondialdehyde, and expressions of P-selectin, fibrinogen and phosphatidylserine were significantly higher, whereas nitrite and expression of apolipoproteins A1/B were significantly lower in hyperlipidemics than in the healthy group. In both groups, clopidogrel significantly reduced aggregation and expression of fibrinogen, but it elevated nitrite levels. Clopidogrel significantly decreased P-selectin and phosphatidylserine expression and malondialdehyde but increased expressions of apolipoproteins A1/B only in hyperlipidemics.
CONCLUSION: It seems that clopidogrel has some new in vitro antiplatelet effects. The present study is a basic in vitro study to suggest new insights into the effects of clopidogrel on platelet functions.

CASE REPORT
8. A rare extramedullary involvement in myeloma: lung parenchyma and association with unfavorable chromosomal abnormalities
Özlem Şahin Balçık, Murat Albayrak, Simten Dağdaş, Funda Ceran, Gülsüm Özet, Funda Demirağ, Osman Yokuş
doi: 10.5152/tjh.2010.08  Pages 109 - 112
Although pulmonary complications developing secondary to lung infections and involvement in ribs occur frequently in multiple myeloma (MM), involvement of the lung parenchyma is quite rare. In clinical studies, the involvement of lung parenchyma has been found to be associated with unfavorable prognosis. Here, a MM case in whom involvement of lung parenchyma was accompanied by unfavorable prognostic cytogenetic markers is presented.
A 62-year-old male presented with complaint of cough, and heterogeneous hypodense mass was detected in thorax computerized tomography. The patient underwent bronchoscopic biopsy. Pathological examination revealed diffuse plasma cell infiltration staining with kappa immunohistochemically. In bone marrow biopsy, plasma cell infiltration was observed. In conventional cytogenetic examination, hypodiploidy was established. In cytogenetic examination carried out with fluorescence in situ hybridization, deletion (13q) was determined. In conclusion, in patients diagnosed with MM and presenting with pulmonary mass lesion, lung involvement associated with plasma cell infiltration should also be considered in the differential diagnosis. As overall survival is low in these cases, more aggressive treatment approaches such as high-dose treatment should be immediately considered.

9. Complex cytogenetic findings in the bone marrow of a chronic idiopathic myelofibrosis patient
Tuğçe Bulakbaşı Balcı, Meltem Yüksel, Zerrin Yılmaz, Feride İffet Şahin
doi: 10.5152/tjh.2010.09  Pages 113 - 116
Chronic idiopathic myelofibrosis is a myeloproliferative disorder characterized by splenomegaly, myeloid metaplasia and reactive bone marrow fibrosis. Karyotype analysis of the bone marrow is an integral part of the diagnosis, especially as a discriminative tool in ruling out reactive conditions. The frequency of clonal cytogenetic anomalies in this disease is the highest among its group, varying between 30 and 75%. Among these, trisomy 1q, 20q-, 13q- and +8 are the most common aberrations. Here we report a 66-year-old male patient whose bone marrow biopsy revealed signs of chronic myeloproliferative changes and dysmegakaryopoiesis. He was administered hydroxyurea treatment, splenic radiotherapy and multiple transfusions. The patient worsened in the following months and the second bone marrow biopsy revealed myelofibrosis. Cytogenetic analysis of this bone marrow sample revealed a complex karyotype reported to be 46,XY,del(9)(q22q34),t(8;17;21)(q22;q21;q22)[23]/46,XY[2], with a previously undefined three-way translocation and deletion in chromosome 9. The patient died shortly thereafter.

10. An unusual presentation of pediatric acute lymphoblastic leukemia with parotid gland involvement and dactylitis
Şule Ünal, Barış Kuşkonmaz, Yasemin Işık Balcı, Bülent Cengiz, Murat Tuncer, Aytemiz Gürgey, Erman Cilsal, Ayşe Gültekingil, Fatma Gümrük
doi: 10.5152/tjh.2010.10  Pages 117 - 119
Mumps infection during the course of childhood acute lymphoblastic leukemia (ALL) treatment has been reported to have a mild course and this was related to the intrinsic low cytopathological effect of the virus, contrasting with the severe course of measles and Varicella zoster virus infections in immunocompromised patients. Herein, we present a three-year-old girl, who was previously vaccinated against mumps infection, admitted with bilateral parotid swelling, dactylitis and serum immunoglobulin M positivity for mumps infection and diagnosed to have ALL with bilateral persistent parotid involvement, inconsistent with mumps infection. Acute leukemia should be suspected during the atypical course of any disease during childhood. Besides, mumps infection at presentation of ALL, as similar to infection emerging during the period of the leukemia treatment, has a mild course.

11. First observation of Hb Tunis [beta124(H2)Pro>Ser] in Turkey
Aylin Köseler, Hasan Koyuncu, Onur Öztürk, Anzel Bahadır, Sanem Demirtepe, Ayfer Atalay, Erol Ömer Atalay
doi: 10.5152/tjh.2010.11  Pages 120 - 122
Hb Tunis [beta124(H2)Pro>Ser] was reported from Tunisia in 1988. This hemoglobin variant was detected by isoelectric focusing moving just ahead of Hb A. It cannot be identified by standard hemoglobin electrophoresis due to its similar mobility to Hb A. It has normal stability and oxygen affinity and does not produce any clinical symptoms. Here, we report a heterozygous Hb Tunis [beta124(H2)Pro>Ser] case discovered for the first time in Turkey in a premarital screening program. This hemoglobin variant can be identified with high performance liquid chromatography analysis confirmed with DNA sequencing. We emphasize in our study the importance of an interdisciplinary collaborative study at the provincial basis for the success of the hemoglobinopathy control program.

LETTER TO EDITOR
12. Ribosomal protein S19 - 631 insertion is an African-originated mutation
Özge Cumaoğulları, Ayşenur Öztürk, Nejat Akar, Solaf Elsayed, Ezzat Elsobky, Bakhouche Houcher
doi: 10.5152/tjh.2010.12  Pages 123 - 124
Abstract |Full Text PDF

13. Lower FXII activity and thrombosis: a comment
Viroj Wiwanitkit
doi: 10.5152/tjh.2010.13  Page 125
Abstract |Full Text PDF

14. IgA lambda oligoclonal gammopathy in multiple myeloma
İbrahim Tek, Dilsa Mızrak, Güngör Utkan, Selami Koçak Toprak, Hüseyin Tutkak, Abdullah Büyükçelik, Bulent Yalçın, Hakan Akbulut, Fikri İçli
doi: 10.5152/tjh.2010.14  Pages 126 - 127
Abstract |Full Text PDF

15. Blood transfusion services in Iraq; an unfortunate field
Abbas Hashim Abdulsalam
doi: 10.5152/tjh.2010.15  Pages 128 - 129
Abstract |Full Text PDF

16. Mega-dose methylprednisolone in hematologic and non-hematological disorders
Şinasi Özsoylu
doi: 10.5152/tjh.2010.16  Pages 130 - 131
Abstract |Full Text PDF

17. Oseltamivir and G6PD deficiency
Şinasi Özsoylu
doi: 10.5152/tjh.2010.17  Page 132
Abstract |Full Text PDF

18. FLT3 - ITD positive acute lymphocytic leukemia, does it impact on disease´s course?
Sebastian Kobold, Nerbil Kılıç, Nerbil Kılıç, John Scharlau, Carsten Bokemeyer, Walter Fiedler
doi: 10.5152/tjh.2010.18  Pages 133 - 134
Abstract |Full Text PDF

IMAGES IN HEMATOLOGY
19. Pleural fluid plasmacytosis in a patient with plasma cell leukemia
Raihan Sajid, Bushra Moiz, Nausheen Kamran, Salman Naseem Adil
doi: 10.5152/tjh.2010.19  Pages 135 - 136
Abstract |Full Text PDF