E-ISSN: 1308-5263
Turkish Journal of Hematology - Turk J Hematol: 24 (1)
Volume: 24  Issue: 1 - 2007
REVIEW
1. Clinical research in Turkey
Hamdi Akan
Pages 1 - 3
The History of Clinical Drug Trials in Turkey The history of clinical trials in Turkey dates back to the beginning of the 20th century, but many years had passed with studies done with no compliance to the Good Clinical Practice (GCP) guidelines. This was not due to the lack of legal documents. On the contrary, the first mention of clinical trials in a legal document occurred in 1926; “The Code of Pharmaceutical Products and Preparations No. 1262” law carried the statement: “Experimental drugs can be used in a patient only by his/her permission.”

RESEARCH ARTICLE
2. Seropositivity rates of HBsAg, anti-HCV, anti-HIV and VDRL in blood donors in Eastern Turkey
İmdat Dilek, Cengiz Demir, Ali Bay, Hayrettin Akdeniz, Ahmet Faik Öner
Pages 4 - 7
Infections caused by hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency viruses (HIV) remain the leading most important health problems worldwide. Screening tests such as HBsAg, anti-HCV, anti-HIV and VDRL are mandatory tests to look at before transfusion of blood or blood components. In this study, donors who applied to our Blood Center in a nine-year period were retrospectively evaluated with respect to HBsAg, anti-HCV, anti-HIV and syphilis seroprevalence. HBsAg, anti-HCV and anti-HIV were examined by microparticle ELISA system, and syphilis antibodies were screened by a syphilis test device. Of the total 39,002 individuals, 16,601 (42%) were females and 22,401 (58%) were males. HBsAg positivity was found in 2.55%, anti-HCV in 0.17%, anti-HIV in 0.036%, and VDRL in 0.057% of overall donors. As a result, HBsAg, anti-HCV, anti-HIV and VDRL seropositivity rates in donors living in our region were found lower than those in many regions of Turkey. Nevertheless, because there is no screening method to reduce the risk resulting from transfusion to zero, it appears that it is essential to adopt strict criteria in the selection of donors and to avoid unnecessary transfusion.

3. Late Endocrine Side Effects in Children with Acute Leukemia
Mustafa Büyükavcı, Nazan Çetingül, Şükran Darcan, Mehmet Kantar, Kaan Kavaklı
Pages 8 - 13
This study was carried out in 28 patients (10 female, 18 male) diagnosed with acute leukemia, and aimed to investigate the abnormalities of endocrine system. Twenty-five of 28 patients were acute lymphoblastic leukemia and 3 were acute non-lymphocytic leukemia. Sixteen children were treated using BFM-90 chemotherapy protocol, and the rest with various regimens. Two patients were exposed to 12-13 Gy of total body irradiation followed by bone marrow transplantation. All patients were in remission at least five years. One (3%) of 28 patients had short stature and 4 (14%) had obesity. Pubertal status was retarded in 2 (7%) patients. Glucose intolerance, secondary hypothyroidism and hypergonadotropic hypogonadism were detected in 2, 1 and 2 patients, respectively. TSH response to TRH test was exaggerated in 1 and blunted in 3 patients.

4. T102C polymorphism of the serotonin (5-HT) 2A receptor gene in Turkish children with cerebral infarct
Buket Nebiye Dönmez, Serap Teber, Gülhis Deda, Nejat Akar
Pages 14 - 17
Platelet-dependent thromboembolism is an underlying mechanism in the pathogenesis of stroke. 5-HT2A receptor gene is expressed in human platelet, coronary artery (blood vessels) and brain. A polymorphism T102C at the 5-HT2A receptor gene was found that may possibly affect the 5-HT2A receptor function. As there is no existing data on T102C variant of 5-HT2A receptor gene in pediatric stroke, we aimed to study in this case-control study whether there is a association between this polymorphism and pediatric stroke. 111 patients (10 months-18 years old) with cerebral infarct and 79 healthy control was included to our study. Polymerase chain reaction (PCR) of the T102C alteration at the 5-HT 2A receptor gene was performed. Our data revealed that, 5-HT (2A) receptor T102C polymo phism was not associated with pediatric stroke in our population either alone or in combination with underlying pro thrombotic factors. However, this needs to be clarified with further studies.

5. Fibrinogen concentration: A marker of cardiovascular disorders in Nigerians
Olutayo Ifedayo Ajayi, Adekunle Ademola Famodu, Efosa Oviasu
Pages 18 - 22
Fibrinogen, one of the most hemorheologically active plasma proteins, is associated with several cardiovascular risk factors, and the plasma concentration can alter dramatically during acute phase response and in a wide variety of clinical conditions. We have assessed fibrinogen levels in some known cardiovascular disorders, during usage of contraceptive pills, acute phase conditions and pregnancy. Our results from patients with various disease conditions indicate that fibrinogen levels are in the pathological range and are significantly higher than in healthy controls (p<0.001). It is concluded that although Africans have low predisposition to thrombosis, they may well be pre-disposed to abnormal fibrin formation which could lead to various thromboembolic complications.

6. Synergistic effect of imatinib mesylate and fludarabine combination on Philadelphia chromosome-positive chronic myeloid leukemia cell lines
Özden Pişkin, Mehmet Ali Özcan, Güner Hayri Özcan, Halil Ateş, Fatih Demirkan, İnci Alacacıoğlu, Bülent Ündar
Pages 23 - 27
Fludarabine-containing combinations have additive cell killing against leukemic blasts in vitro. It has also been shown that imatinib mesylate combined with fludarabine or cladribine had an additive effect on CML CFU-GM cells. In this regard, we aimed to investigate the effect of fludarabine-imatinib mesylate combination against CML blastic phase cell lines K562 and Meg-01. XTT test was performed for proliferation and inhibition assay. According to obtained data, five different effective concentrations of each drug in 25 different combinations were tested. Results of the combination studies were analyzed with isobologram. At IC20, imatinib mesylate and fludarabine combination showed synergism and strong synergism in K562 and Meg-01 cells, respectively. At IC50 and IC75, combination indexes (CI) indicated strong synergism and synergism. Based on our results, the fludarabine- based chemotherapy regimens can be used for those patients with CML blastic phase in combination with imatinib mesylate.

CASE REPORT
7. A case of Cauda Equina syndrome in a leukemic patient due to intrathecal methotrexate
Elif Birtaş Ateşoğlu, Tülin Fıratlı Tuğlular, Cafer Adıgüzel, Işık Kaygusuz, Figen Noyan, Mustafa Çetiner, Mahmut Bayık
Pages 28 - 31
The leukemias may cause neurologic dysfunction through either direct invasion of the nervous system or indirectly through cytopenias, or it may occur as a result of the necessarily vigorous treatment programs for leukemia. We report here a 24-year-old acute lymphoblastic leukemia patient who in her second cycle of hyper-CVAD chem therapy regimen (high-dose Ara-C and high-dose methotrexate) received intrathecal methotrexate and two days afterwards was diagnosed as having Cauda Equina syndrome (CES). A lumbo-sacral MRI imaging with gadolinium was performed and there was a remarkable enhancement in the Cauda Equina region, suggesting either leukemic involvement or a type of neurologic complication associated with intrathecal methotrexate treatment. To rule out leukemic involvement, a lumbar puncture was performed and the CSF was free of leukemic cells. There are cases of CES developing after spinal anesthesia reported in the literature, but this is the first report of CES due to intrathecal methotrexate.

8. Intense myelofibrosis in a child: unusual result of EBV-associated hemophagocytic lymphohistiocytosis
Bülent Karapınar, Deniz Yılmaz, Yeşim Aydınok, Ebru Türkoğlu, Mine Hekimgil, Kaan Kavaklı
Pages 32 - 35
A previously healthy 12-year-old girl was admitted to the intensive care unit with severe pulmonary bleeding. Her history revealed that she had suffered from high fever, fatigue, sore throat, myalgia and generalized rash for two weeks. Physical examination revealed hepatosplenomegaly. Laboratory investigation showed pancytopenia associated with unusual high levels of serum ferritin, triglyceride and lactate dehydrogenase (LDH) and low fibrinogen levels. Apparent hemophagocytosis was seen in bone marrow aspiration. Bone marrow biopsy revealed myelofibrosis, and confirmed hemophagocytosis. IgM for Epstein-Barr virus (EBV) viral capsid antigen was found to be positive. She received chemotherapy for 10 days according to hemophagocytic lymphohistiocytosis (HLH)-2004 treatment protocol, since the symptoms persisted despite supportive therapy and intravenous immunoglobulin (IVIG) administration. However, the clinical status and laboratory findings did not respond to treatment and she died from severe pulmonary bleeding associated with prolonged ventilator support and sepsis. Intense myelofibrosis, which is reported rarely, particularly in patients with EBV-related HLH, contributed to this fatal prognosis.

IMAGES IN HEMATOLOGY
9. Bone marrow necrosis in a patient receiving high dose chemotherapy for ALL
Ahmet İfran, Mükerrem Safalı, Kürşat Kaptan, Cengiz Beyan
Page 36
Abstract |Full Text PDF

LETTER TO EDITOR
10. A further case of Hb J-Iran [beta77(EF1)His->Asp] in Muğla, Turkey
Nejat Akar, Ece Akar, Sibel Özdemir
Pages 37 - 38
Abstract |Full Text PDF