Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 9 4 2016 02 09 165 172 EN Ehsan Mohajeri Department of Pharmaceutics, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran Behjat Kalantari-Khandani Department of Oncology and Hematology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran Abbas Pardakhty Pharmaceutics Research Center, Kerman University of Medical Sciences, Kerman, Iran Moeinadin Safavi Department of Pathology, Afzalipour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran Mehdi Ansari Department of Pharmaceutics, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran 2015 10 13 2015 10 13  Background: Imatinib is known as the drug of choice for treatment of chronic myeloid leukemia (CML). For adults the recommended daily dosage of 400 mg requires simultaneous intake of up to four capsules or tablets each 100 mg. A new 400 mg film coated tablet developed due to the need to swallow multiple capsules or tablets per dose and that was a negative impact on treatment adherence. Subjects and Methods: A group of 36 patients were randomly assigned to receive Imatinib as 4×100 mg capsules, 4×100 mg tablets, and 1×400 mg tablet. Blood sampling was performed for up to 48 h after first dosing. After that, subjects were monitored to assess drug related adverse events. Pharmacokinetic parameters were assessed using concentration-time curves for plasma Imatinib and its metabolite. Results: Mean area under the curve (AUC (0–∞)) values were 27011, 25811 and 25699 ng/ml for 4×100 mg capsules, 4×100 mg tablets, and 1×400 mg tablets, respectively. Cmax values were 1548, 1605 and 1622 ng/ml, and t1/2 values were 15.7, 15.8 and 15.6 h. The Test/Reference ratios for AUC (0–∞), AUC (0–48), and Cmax were 0.99, 0.99 and 1.02 for 4×100 mg tablets versus 4×100 mg capsules and 0.96, 0.96 and 0.99 for 1×400 mg tablet versus 4×100 mg capsules. The 95% confidence intervals were fully contained within the accepted interval. The mild and moderate adverse events considered to be drug related were reported. These events showed no clustering by type of dosage form and were of little to no clinical significance. Conclusion: Film coated (400 mg) tablet dosage formulations of Imatinib is bioequivalent to the commercial available 100 mg hard gelatin capsule, and is as safe and well tolerated. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/352 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/352/433

Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 9 4 2016 02 09 173 179 EN Mehdi Mohammadi Clinical Pharmacy Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Mohammad Vaezi Hematology-Oncology and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran Bahram Chahardouli Hematology-Oncology and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran Molouk Hadjibabaie Research Center for Rational Use of Drugs, Tehran University of Medical Sciences, Tehran, Iran. AND Clinical Pharmacy Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Ardeshir Ghavamzadeh Hematology-Oncology and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran 2015 10 15 2015 10 15 Background: Despite recent advances in mobilization techniques, a considerable portion of patients fail to mobilize sufficient number of cells for successful autologous stem cell transplantation. There are several studies available that have demonstrated enhanced mobilization of endothelial progenitor cells with atorvastatin. Therefore, this prospective trial was conducted to evaluate the mobilizing effect of atorvastatin on hematopoietic progenitor cells. Subjects and Methods: Forty-four autologous HSCT candidates were randomized in a double-blind controlled trial to receive atorvastatin 40 mg daily or placebo plus standard G-CSF regimen. Treatment was initiated at the time of hospitalization and continued until the day of cell harvest. Independent-samples T-Test, Repeated Measures ANOVA and Mann-Whitney U test were performed to compare means. Categorical variables were analyzed using Chi-square and Fisher’s exact test. Results: Mean number of hematopoietic progenitor cells per microL of peripheral blood at the time of cell harvest did not differ significantly between the two groups. There was no statistically significant difference in secondary outcomes like time of platelet or PMN engraftment, occurrence of bleeding or infectious episode, duration of hospitalization and etc. Conclusion: The results of this study did not support beneficial effects of atorvastatin on mobilization of hematopoietic progenitor cells from bone marrow. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/468 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/468/441

Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 9 4 2016 02 09 180 184 EN Alireza Abdollahi Associate Professor of Pathology, School of Medicine, Imam Khomeini Hospital Complex, Tehran University of Medical sciences. Tehran, Iran Abbas Alibakhshi Assistant Professor of Surgery, Imam Khomeini Hospital Complex, Vali-Asr Hospital, Surgery Ward, Tehran University Medical of sciences Tehran, Iran. Zahra Farahani Physiologists, Maternal Fetal and Neonatal Research Center, Tehran University Medical of Sciences, Tehran, Iran 2015 10 13 2015 10 14 Background: Breast cancer is the most common invasive cancer in females worldwide. It accounts for 16% of all female cancers and 22.9% of invasive cancers in women. 18.2% of all cancer deaths worldwide including both males and females are from breast cancer. In this study we compared few serum elements in patients with benign and malignant breast tumor to find any related prognostic and predictive value. Subjects and Methods: A case-control study was carried out in a hospital (Tehran - Iran) in 2012. Target population was divided in 2 groups; subjects with benign and malignant breast tumors. We did preoperative hematological test. Five milliliter fasting blood vein was collected, centrifuged in 3000 g for 15 minutes to obtain serum. We measured serum Calcium (Ca), Phosphorus (P), Magnesium (Mg), Zinc (Zn), and high sensitive-CRP, analyzed statistically and compared recorded elements in 2 groups by software package SPSS version 16. The level of significant was considered P < 0.05. Results: Of 87 women, 49 cases with benign breast disease (group A) and 38 cases with breast cancer (group B) entered our study. Serum concentration of Ca, mg, and P in group A were higher than group B, however these differences were not significant. We found no significant correlation between serum Zn and type of tumor in our patients. On the other hand, a significant elevation in hs-CRP in patient with breast cancer was seen (P Value=.000). Conclusion: Our results have shown similar concentration of Ca, Mg, Zn, P and completely different hs-CRP concentration in patients with benign and malignant breast disease. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/363 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/363/435

Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 9 4 2016 02 09 185 192 EN Behzad Poopak DCLS,PhD in Hematology, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran Saghar Rabieipoor MSc in Biotechnology, Payvand Clinical and Specialty Laboratory, Tehran, Iran Nazila Safari MSc in Molecular Oncology, Payvand Clinical and Specialty Laboratory, Tehran, Iran Emadedin Naraghi MSc in Bioscience, Payvand Clinical and Specialty Laboratory, Tehran, Iran Fatemeh Sheikhsofla MSc in Cell and Molecular Biology, Payvand Clinical and Specialty Laboratory, Tehran, Iran Gelareh Khosravipoor MD, Payvand Clinical and Specialty Laboratory, Tehran, Iran 4MSc in Bioscience, Payvand Clinical and Specialty Laboratory, Tehran, Iran 2015 10 14 2015 10 14 Background: Although catalytic properties of different genetic polymorphisms of VKORC1 and CYP2C9 products have been identified, there is limited study available regarding warfarin dose requirement in Iranian patient population. This study investigates the impact of these polymorphisms on 115 patients, referred to Payvand Clinical and Specialty Laboratory for determining the appropriate dose of warfarin. Results of the study may be applicable to individuals who are under warfarin therapy to avoid warfarin resistance or intolerance. Subjects and Methods: PT-INR test was utilized as a screening method. Genotyping were performed for VKORC1 and CYP2C9 using PCR method. Statistical analyses including unpaired t-test or ANOVA and regression were done using SPSS. Results: VKORC1 GA was the most common genotype of VKORC1 allele among the study samples, with a rate of 57.4%. In CYP2C9 variant, 20% and 14.8% of subjects carried CYP2C9*1/*2 and CYP2C9*1/*3 genotyping, respectively. By contrast, the WT *1/*1 genotype was more abundant and dominant. The high frequency of VKORC1 (_1639) GA genotype (57.4%), was significant versus for the rest of the cohort (42.6%). In addition, a significant relationship was found between CYP2C9*1 and drug dose (P>0.021). Conclusion: In this study, samples were characterized by higher frequencies of CYP2C9*1 and VKORC1 G/A, determined as higher warfarin taking doses. The results showed a significant relationship of the VCORC1 and CYP2C9 polymorphisms with warfarin sensitivity and severe side effects. Estimating right doses of warfarin to prescribe can help to reduce the risk of over- or under-anticoagulation and subsequently, the risk of thromboembolism or bleeding. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/370 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/370/443

Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 9 4 2016 02 09 193 197 EN Mahender Kumar Assistant Professor, Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Uttar Pradesh, India Man Updesh Sachdeva Associate Professor, Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India Shano Naseem Assistant Professor, Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India Jasmina Ahluwalia Additional Professor, Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India Reena Das Professor, Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India Neelam Varma Professor and Head, Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India RK Marwaha Professor, Department of Pediatrics (Hematology-Oncology Unit), Postgraduate Institute of Medical Education and Research, Chandigarh, India 2015 10 17 2015 10 19 Background: Langerhans' cell histiocytosis (LCH) is a reactive proliferative disease of unknown pathogenesis characterized by proliferation of Langerhans cells. Involvement of bone marrow (BM), liver and lung are related to high risk factors and poor survival. The aim of this report is to highlight the clinical and haematological findings of 5 cases of LCH with BM infiltration which may help to predict involvement of BM. Case series: Five cases of Langerhan’s cell histiocytosis with bone marrow infiltration were retrieved from archives of Department of Hematology, PGIMER and Chandigarh for review and further analysis.Male to female ratio was 3:2 with mean age of 9.4 months. Two out of 5 patients had obvious skull swelling; however, radiography of the skull revealed lytic lesion of skull in 4 cases and 2 had skin rashes. Hepatomegaly was present in 4 cases and 2 of whom also had lymphadenopathy and splenomegaly. All patients had anaemia at the time of presentation. Bone marrow aspiration and trephine biopsy in all 5 cases revealed infiltration by large histiocytes with abundant cytoplasm and coffee bean shaped nucleus. Nodules of these Langerhans cells with admixture of eosinophils were seen on trephine biopsy. Immunohistochemistry showed positivity for CD1a stain. Conclusion: BM evaluation is important in LCH patients to categorize disease which further determines the type of therapy to be given. Clinical details may help to predict the BM involvement; however, demonstration of CD1a positive cells in marrow is most important tool to diagnose marrow infiltration by LCH. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/475 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/475/436

Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 9 4 2016 02 09 198 202 EN Fereshteh Maryami Biotechnology Research Center, Department of Molecular Medicine, Pasteur Institute of Iran, Tehran, Iran Azita Azarkeivan Pediatric Hematology Oncology, Transfusion Research center, High Institute for Research and Education in Transfusion Medicine, Department of Thalassemia Clinic, Tehran, Iran Mohammad Sadegh Fallah Kawsar Human Genetics Research Center, Tehran, Iran Sirous Zeinali Iranian Molecular Medicine Network, Biotechnology Research Center, Pasteur Institute of Iran, Pasteur St, Tehran, IranKawsar Human Genetics Research Center, Tehran, Iran 2015 10 17 2015 10 17 Background: Thalassemia syndromes are the most prevalent single gene disorders in Iran. This study aimed to evaluate the effect of different types of beta-globin gene mutations, co-inheritance of alpha-globin gene mutations and/or Xmn1 SNP on disease phenotype in a large cohort of Iranian patients. Subjects and Methods: In total, 433 patients were clinically classified into β-thalassemia major (TM) or intermedia (TI). Multiplex PCR, ARMS-PCR, RFLP-PCR and DNA sequencing were performed to identify both α- and β-globin gene mutations and Xmn1 polymorphism as well. All data were compared and analyzed by SPSS software in TM and TI groups consequently. Results: A total of 39 different β-globin mutations were identified. Among them, the most common were IVS IInt1 (40.33%) followed by IVS Int5 (9.56%), C30 (7.22%) and Fr8-9(7%). All patients were subjected to evaluate common α-globin gene deletions. The patients inherite Research Center, Tehran University of Medical Sciences, Tehran, Iran Ashraf Malek Mohammadi Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran Mahdi Zahed Panah School of Allied Medical Sciences, Qazvin University of Medical Sciences, Qazvin, Iran Mohammad Reza Ostadali Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran Hajar Nasiri Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran Ardeshir Ghavamzadeh Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran 2016 04 09 2016 05 16 Background: Mesenchymal stromal cells (MSCs) are employed in various different clinical settings in order to modulate immune response. Human autologous and allogeneic supplements including platelet derivatives such as platelet lysate (PL), platelet-released factors (PRF) and serum are assessed in clinical studies to replace fetal bovine serum (FBS). The immunosuppressive activity and multi-potential characteristic of MSCs appear to be maintained when the cells are expanded in platelet derivatives. Materials and Methods: Platelet-rich plasma was collected from umbrical cord blood (UCB). Platelet-derived growth factors obtained by freeze and thaw methods. CD62P expression was determined by flow cytometry. The concentration of PDGF-BB and PDGF-AB was detemined by ELISA. We tested the ability of a different concentration of PL-supplemented medium to support the ex vivo expansion of Wharton's jelly derived MSCs. We also investigated the biological/functional properties of expanded MSCs in presence of different concentration of PL. The conventional karyotyping was performed in order to study the chromosomal stability. The gene expression of Collagen I and II aggrecan and SOX-9 in the presence of different concentrations of PL was evaluated by Real-time PCR. Results: We observed 5% and 10% PL, causing greater effects on proliferation of MSCs .These cells exhibited typical morphology, immunophenotype and differentiation capacity. The genetic stability of these derivative cells from Wharton's jelly was demonstrated by a normal karyotype. Furthermore, the results of Real-time PCR analysis showed that the expression of chondrocyte specific genes was higher in MSCs in the presence of 5% and 10% PL, compared with FBS supplement. Conclusions: We demonstrated that PL could be used as an alternative safe source of growth factors for expansion of MSCs and also maintained similar growing potential and phenotype without any effect on chromosomal stability. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/593 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/593/507

Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 10 3 2016 06 28 172 185 EN Shaban Alizadeh Hematology Department, School of Allied Medicine, Tehran University of Medical Sciences, Tehran, Iran Seyed Ghader Azizi Hematology Department, School of Allied Medicine, Tehran University of Medical Sciences, Tehran, Iran Masoud Soleimani Hematology Department, School of Medicine, Tarbiat Modares University, Tehran, Iran Yadollah Farshi Hematology Department, School of Allied Medicine, Tehran University of Medical Sciences, Tehran, Iran Zahra Kashani khatib Hematology Department, School of Medicine, Tarbiat Modares University, Tehran, Iran 2015 10 18 2015 12 17 MiRs are 17-25 nucleotide non-coding RNAs. These RNAs target approximately 80% of protein coding mRNAs. MiRs control gene expression and altered expression of them affects the development of cancer. MiRs can function as tumor suppressor via down-regulation of proto-oncogenes and may function as oncogenes by suppressing tumor suppressors. Myeloproliferative neoplasias (formerly known as chronic myeloproliferative disorders) form a class of hematologic malignancies demonstrating the expansion of stem cells in one or more hematopoietic cell lines. CML results from an acquired translocation known as BCR-ABL (Philadelphia chromosome). JAK2V617F mutation is present in over 95% of PV, 55% of ET and 65% of PMF cases. Aberrant expression of miR is associated with myeloproliferative neoplasias, pathogenesis, disease progress and response to treatment. MiRs can also be potential therapeutic targets. CML is mainly treated by tyrosine kinase inhibitors such as Imatinib. In addition, altered function of miRs may be used as a prognostic factor in treatment. Resistance to Imatinib is currently a major clinical problem. The role of a number of miRs has been demonstrated in this resistance. Changing expression pattern of miRs can be effective in response to treatment and inhibition of drug resistance. In this paper, we set out to evaluate the effect of miRs in pathogenesis and treatment of MPN. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/476 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/476/508

Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 10 3 2016 06 28 186 190 EN Ratnam Nookala Department of Hematology-Oncology, Prince George’s Medical Center, Cheverly, Maryland, USA Vera Batchu Department of Hematology-Oncology, Prince George’s Medical Center, Cheverly, Maryland, USA Heather Lee Radiation Oncology, Doctors Regional Cancer Center, Lanham, Maryland, USA Amir Loghmani Department of Hematology-Oncology, Prince George’s Medical Center, Cheverly, Maryland, USA Gurdeep Chhabra Department of Hematology - Oncology, Prince George’s Medical Center, Cheverly, Maryland, USA 2015 12 08 2015 12 23 Intraocular metastatic tumors have been increasingly reported in the recent past. Unlike choroidal metastasis, metastasis to retina is very rare and so far has been reported in very few case reports only. A 56 year-old male who presented with a history of adenocarcinoma of the cecum and underwent lap colectomy for the primary cecal tumor, received adjuvant chemotherapy for a year after surgery and decided to stop. He was also diagnosed with metastasis to liver and lung at this time. He presented with left eye pain, pressure and decreased vision suspicious for retinal metastasis from cecal primary lesion, 2 years after initial diagnosis. A mass of 5 x 10 mm was found on ophthalmoscopic examination and on ultrasound of the eye, in spite of normal results of MRI of the orbit. Palliative radiation therapy of the left eye resulted in decreased eye pressure and improved vision. As retinal metastasis carries a poorer prognosis due to higher risk of spread to central nervous system, the diagnosis of retinal metastasis in ca