NLR, PLR, and HPR as novel diagnostic biomarkers for Acute Lymphoblastic Leukemia 2 2 Background: Acute lymphoblastic leukemia (ALL) causes uncontrolled cell proliferation and prevents normal cell differentiation at any stage of hematopoiesis. Therefore, timely diagnosis and treatment are very important. Complete blood count (CBC) can be a simple, but valuable initial test to diagnose ALL. In this study, we investigated the diagnostic value of hematological parameters, including Platelet to lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and hemoglobin to Platelet ratio (HPR) indices in ALL. Methods: In this study, 54 ALL patients (Mean ages: 5.29) and 58 healthy controls (Mean ages: 5.53) were evaluated. They were compared in terms of hematological parameters, including PLR, NLR, and HPR; cytogenetic and immunophenotypes were also analyzed. Result: In the analysis of hematological factors between the studied groups, all indices except lymphocytes showed a statistically significant relationship (P-Value ˂0.05). In terms of hematological factors, only WBC and ESR were statistically significant between the B-ALL and T-ALL groups (P-Value ˂0.05). The ROC curve was generated to select the appropriate cut-off values for NLR, PLR, and HPR based on analysis. NLR and PLR have cut-off values of 0.50 and 62.24, respectively; they are good biomarkers to distinguish ALL individuals from normal people. HPR value was significant between case and control groups, but it was not a suitable indicator for distinguishing patients from the control group. Conclusion: CBC is a simple and valuable test for early detection of ALL, and the new PLR and NLR markers are good hematologic markers for ALL diagnoses. 80 87 2023/04/13 1402/1/24 2023/06/24 1402/4/3 Bahareh Moghimian Bahareh Moghimian Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran bahar.moghimian.74@gmail.com Ahmad Jafari-joshaghan Ahmad Jafari-joshaghan Department of Pathology, Faculty of Medicine, University of Medical Sciences, Mashhad, Iran Jafarijoshaghan@gmail.com Hossein ayatollahi Hossein ayatollahi Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran ayatollahih@mums.ac.ir Fatemeh Shams Fatemeh Shams Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Iranian Blood Transfusion Organization (IBTO), Tehran, Iran shams8869@yahoo.com Narjes Soltani Narjes Soltani Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran narjessoltanei@gmail.com Fatemeh Ahmadpour Fatemeh Ahmadpour Nutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran ahmadpourfatimaa@gmail.com Sepideh Shakeri Sepideh Shakeri Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran se.shakeri@yahoo.com Mohammadreza Javan Mohammadreza Javan Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Iranian Blood Transfusion Organization (IBTO), Tehran, Iran javaneee@gmail.com Acute lymphoblastic leukemia Complete blood count Diagnostic biomarker NLR PLR. ## ##

Guideline for the diagnosis and treatment of hypothyroidism and hypoparathyroidism in patients with blood transfusion-dependent thalassemia 2 2 Iron overload can adversely affect thyroid and parathyroid function in patients with transfusion-dependent thalassemia. Iron deposition in both glands or the pituitary gland, which controls thyroid function, can lead to their destruction and dysfunction. Hypothyroidism can cause symptoms such as fatigue, weight gain, and depression, while hypoparathyroidism can cause symptoms such as numbness and tingling in the hands and feet, muscle cramps, and seizures. Regular thyroid and parathyroid function monitoring is essential in thalassemia patients to detect any dysfunction early and provide appropriate treatment. Treatment may include medications to replace thyroid hormone or calcium and vitamin D supplements to manage hypoparathyroidism. A comprehensive approach to managing endocrine complications in thalassemia patients can improve outcomes and quality of life for these individuals. To provide professional healthcare members with clear and concise recommendations for diagnosing and treating hypothyroidism and hypoparathyroidism in transfusion dependent thalassemia patients, a practical national guideline should be developed. 89 96 2023/04/132023/04/7 1402/1/18 2023/06/242023/05/20 1402/2/30 Nahid Hashemi-madani Nahid Hashemi-madani Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran. nahid.hashemimadani@gmail.com Neda Rahimian Neda Rahimian Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran. rahimian.n@iums.ac.ir Mohammad E. Khamseh Mohammad E. Khamseh Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran. m.e.khamseh@gmail.com Pooya Faranoush Pooya Faranoush Pediatric Growth and Development Research center, Institute of Endocrinology Iran University of Medical Sciences Tehran Iran pooya1375@yahoo.com Mojtaba Malek Mojtaba Malek Research Center for Prevention of Cardiovascular Disease, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran. malekmoj@yahoo.com Fariba Ghasemi Fariba Ghasemi Pediatric Growth and Development Research center, Institute of Endocrinology Iran University of Medical Sciences Tehran Iran fariba.ghasemi@yahoo.com Negin Sadighnia Negin Sadighnia Pediatric Growth and Development Research center, Institute of Endocrinology Iran University of Medical Sciences Tehran Iran negin_sadighnia@yahoo.com Mohammad Reza Foroughi-Gilvaee Mohammad Reza Foroughi-Gilvaee Pediatric Growth and Development Research center, Institute of Endocrinology Iran University of Medical Sciences Tehran Iran emad.foroughi95@gmail.com Seyyed Morteza Alavi Seyyed Morteza Alavi Department of Clinical Science, Faculty of Specialized Veterinary Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran seyedmortezaalavi3@gmail.com Mohammad Javad Mashayekhnia Mohammad Javad Mashayekhnia Department of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, Islamic Azad University, Babol Branch, Tabriz, Iran mojmashayekh@gmail.com Mahdi Bashizade Mahdi Bashizade Department of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran. M.bashizade@ut.ac.ir Mohammad Reza Roudaki Sarvendani Mohammad Reza Roudaki Sarvendani Department of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran. mroudaki.7@ut.ac.iR Elham Ebrahimi Elham Ebrahimi Department of Clinical Science, Faculty of Specialized Veterinary Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran eli.ebrahimi@rocketmail.com Mohammad Faranoush Mohammad Faranoush Pediatric Growth and Development Research center, Institute of Endocrinology Iran University of Medical Sciences Tehran Iran. faranoush47@gmail.com Transfusion Dependent Thalassemia Hypothyroidism Hypoparathyroidism Iron overload Iron chelators ## ##

Plasma industry in Iran: Challenges and opportunities 2 2 Several studies have demonstrated the undeniable value of plasma as the source of myriads of proteins with numerous biological activities, many of which might not be discovered yet. Plasma fractionation is a process aiming at the production of plasma-derived medicinal products (PDMPs) such as gamma globulins (immunoglobulin [Ig]), hyperimmune serum globulins, albumin, and clotting and coagulation factors like Factor VIII (FVIII) and FIX. Despite several challenges in the evolution of the plasma industry, there is still worldwide increasing demand for PDMPs with the proof that the market size value of this industry is estimated at 28.69 billion dollars in 2021. In Iran, the plasma industry began its journey with the initial activities of the Iranian Blood Transfusion Organization (IBTO). Regarding the expense of establishing companies for plasma fractionation and elevating demands of PDMP in Iran’s health system, decision-makers implemented contract fractionation which not only supply the needs of the country but also cause significant savings in financial resources. Although the amount of collected plasma has been raised, more than 400,000 liters of collected plasma is still half of the required amount as Iran’s demand for FVIII and albumin is over the supply. Putting together these data that the clinical indications for PDMPs, particularly IVIg, are growing (as seen in COVID-19) and commercially purchasing products is not economically beneficial, it is necessary for Iran’s policymakers to invest in the plasma industry by establishing more plasmapheresis centers and raising people’s awareness to donate more amount of plasma in order to elevate the levels of plasma collection annually. Moreover, entering the industry of fractionation by localization of this science and construction of fractionation plants should be on the agenda. 97 112 2023/04/132023/04/72023/04/25 1402/2/5 2023/06/242023/05/202023/05/17 1402/2/27 Mohammad-Javad Sanaei Mohammad-Javad Sanaei Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran Hassan Abolghasemi Hassan Abolghasemi Pediatric Congenital Hematologic Disorders Research Center, Mofid Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran Plasma industry Plasma-derived medicinal products PDMP Fractionation Market ## ##

The dispersion of pediatric cancer biobanks in the Middle East: a global review of available resources 2 2 Background: Pediatric cancer biobanks play an important role in advancing cancer research efforts and developing effective treatments. However, the majority of these biobanks are located in developed countries, leaving a large portion of the world's population without access to these critical resources. This article focuses on the current dispersion of pediatric cancer biobanks in the Middle East. Method: PubMed and Google Scholar databases were searched using the terms ‘pediatric cancer biobank’ or ‘childhood cancer biobank’ or ‘children’s cancer biobank’, or ‘pediatric cancer biorepository’ or ‘childhood cancer biorepository’ or ‘children’s cancer biorepository’, along with ‘Jordan’, ‘the United Arab Emirates’, ‘Iran’, ‘Bahrain’, ‘Turkey’, ‘Syria’, ‘Iraq’, ‘Saudi Arabia’, ‘Oman’, ‘Qatar’, ‘Kuwait’, ‘Lebanon’, ‘Egypt’, ‘Yemen’, ‘Palestine’ with English language restriction. Results: Despite being a relatively recent development, some notable pediatric cancer biobanks have been established in the region, including the King Hussein Cancer Center Biobank in Jordan, the Children's Cancer Hospital Egypt Biorepository and Biospecimen Research Facility in Egypt, the Iranian Childhood Cancer Biobank in Iran, and national pediatric cancer biorepository in Qatar. Conclusion: However, several challenges still hinder the establishment and maintenance of biobanks in the region, including insufficient funding, lack of infrastructure and resources, limited awareness, and regulatory hurdles. Overcoming these challenges will require targeted investments, building infrastructure and awareness, and efficient regulatory frameworks. Developing and maintaining high-quality pediatric cancer biobanks within the Middle East could lead to a better understanding of pediatric cancer patterns in the region, ultimately improving treatment outcomes and quality of life for pediatric cancer patients globally. 113 116 2023/04/132023/04/72023/04/252023/04/8 1402/1/19 2023/06/242023/05/202023/05/172023/06/14 1402/3/24 Peyman Eshghi Peyman Eshghi Pediatric Congenital Hematologic Disorders Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran peshghi64@gmail.com Nasrin Dehghan-Nayeri Nasrin Dehghan-Nayeri Pediatric Congenital Hematologic Disorders Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran Nasrindehghan10@gmail.com Pediatric cancer biobank Middle East Cancer Children ## ##

Harnessing the Potential of Vesicular Stomatitis Virus as a Novel Therapeutic Strategy for Cancer Treatment 2 2 Background: Oncolytic virotherapy has emerged as a promising approach for the treatment of various cancers. This review article aims to provide an overview of Vesicular Stomatitis Virus (VSV) as an emerging anti-cancer therapy. Materials and Methods: The article discusses the mechanism of action, preclinical and clinical studies, and challenges in the clinical translation of VSV. It also explores potential strategies to enhance the efficacy and safety of VSV-based oncolytic therapy, including combination therapies and genetic modifications Results: The mechanisms underlying VSV-mediated anti-cancer activity, such as induction of apoptosis, activation of immune responses, and disruption of tumor vasculature, are explored. Additionally, known methods for the preparation of oncolytic VSV, including genetic modifications and combination therapies, are discussed to optimize its anti-cancer effects. Conclusion: Strategies to enhance VSV efficacy and overcome safety challenges are examined, including the use of VSV in combination with other therapies, such as chemotherapy or immunotherapy, as well as the development of novel viral vectors and engineering approaches to improve tumor-specific targeting and minimize off-target effects. In conclusion, this review highlights the potential of VSV as a novel therapeutic strategy for cancer treatment. Harnessing the unique characteristics of VSV, combined with ongoing research and technological advancements, may pave the way for the development of effective and safe VSV-based therapies in the future. 117 127 2023/04/132023/04/72023/04/252023/04/82023/04/24 1402/2/4 2023/06/242023/05/202023/05/172023/06/142023/06/11 1402/3/21 Fatemeh Mousavinasab Fatemeh Mousavinasab Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA fatemeh.kmls@gmail.com Elham Razani Elham Razani 1-Department of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran 2- 3- Scientific board, Colife Integrated Medical Labs, Tehran, Iran e_razani_mls@yahoo.com Vesicular Stomatitis Virus (VSV) Cancer Treatment Oncolytic Virotherapy Combination therapy Oncogene targeting ## ##

Remodeling of Tumor Microenvironment for Enhanced Immunotherapy against Non-Melanoma Skin Cancer 2 2 Non-melanoma skin cancer is a serious malignancy and white-skinned people are highly susceptible to this cancer. About 918 deaths occurred due to NMSC in the UK following the year 2018-2019. The incidence of NMSC is 18-20 times higher as compared to melanoma skin cancer. The tumor immune microenvironment of NMSC possesses a diversity of immune cells that exert pro-tumor and anti-tumor effects on the TIME. So by recognizing the tumor-promoting entities, the TIME can be remodeled. Immunotherapy provides such a treatment that activates the person’s immune system to fight against tumorigenic cells. Radiotherapy also causes the modulation of the immune system and increases the anti-tumor responses in patients. The use of immune checkpoint inhibitors after radiotherapy has produced significant survival rates in patients. Oncolytic virus therapy is a subtype of immunotherapy with a positive response in the treatment of cancer. The synthetic viral promoter is highly specific to tumor and the introduction of transgenes help them to inhibit the tumor-promoting cells and make the tumor susceptible to anti-tumor cells, thus helping the tumor to eliminate from the body. This characteristic of oncolytic virus converts the ‘‘cold TIME’’ to ‘‘hot TIME’’ which exerts a highly positive response when used ICIs. In this article, a literature review is conducted to study the role of TIME in the progression of cancer and various methods that remodel the TIME such as immunotherapy, radiotherapy, and oncolytic viruses that might help to treat NMSC. 128 145 2023/04/132023/04/72023/04/252023/04/82023/04/242023/04/20 1402/1/31 2023/06/242023/05/202023/05/172023/06/142023/06/112023/06/8 1402/3/18 Arooba Farman Farman Arooba Farman Farman University of the Punjab aroobafarman22@gmail.com Skin cancer Tumor microenvironment Immunotherapy Oncolytic viruses Radiotherapy ## ##

Genetics and pathophysiology of severe congenital neutropenias (SCNs) 2 2 Severe congenital neutropenias (SCNs) are the rare heterogenous group of preleukemia bone marrow failure syndromes characterized by impaired differentiation of neutrophilic granulocytes and, as a result, severe chronic neutropenia. Patients with SCN are predisposed to recurrent, often life-threatening bacterial and/or fungal infections beginning in the first months of life. Molecular abnormalities in 10 genes have been identified that are responsible for SCNs. The pathophysiological mechanisms of SCNs are the subject of extensive investigation and are not fully known. The current review aims to summarize the studies exploring the biological role of SCN-associated genes and the effects of mutant genes in neutropenia pathogenesis. We mainly focus on the genetic mutations that lead to SCN1 to SCN9 and X-linked SCN (XSCN) to shed more light on the pathophysiology of these diseases. 146 171 2023/04/132023/04/72023/04/252023/04/82023/04/242023/04/202023/04/24 1402/2/4 2023/06/242023/05/202023/05/172023/06/142023/06/112023/06/82023/06/18 1402/3/28 Samareh Younesian Samareh Younesian Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran samareyounesian@gmail.com Amir-Mohammad Yousefi Amir-Mohammad Yousefi Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran amirmm.yousefi@yahoo.com Peyman Eshghi Peyman Eshghi Pediatric Congenital Hematologic Disorders Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran peyman64@yahoo.com Mohammad Faranoush Mohammad Faranoush Pediatric Growth and Development Research Center, Iran University of Medical Sciences, Tehran, Iran faranoush47@gmail.com Pooya Faranoush Pooya Faranoush Pediatric Growth and Development Research center, Institute of Endocrinology, Iran University of Medical Sciences, Tehran, Iran Bijan Keikhaei Bijan Keikhaei Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur, University of Medical Sciences, Ahvaz, Iran keikhaeib@yahoo.com Aziz Eghbali Aziz Eghbali Clinical Research Development Center of Aliasghar Hospital, Iran University of Medical Sciences, Tehran, Iran aziz_eghbali@yahoo.com Bibi Shahin Shamsian Bibi Shahin Shamsian Pediatric Congenital Hematologic Disorders Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran shahinshamsian@gmail.com Babak Abdolkarimi Babak Abdolkarimi Department of Pediatrics, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran b.abdolkarimi@yahoo.com Sabahat Haghi Sabahat Haghi Department of Pediatrics, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran SabaHaghi@yahoo.com Hassan Abolghasemi Hassan Abolghasemi Pediatric Congenital Hematologic Disorders Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran h.abolghasemi.ha@gmail.com Davood Bashash Davood Bashash Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran david_5980@yahoo.com Neutropenia Severe congenital neutropenia Kostmann syndrome ELANE HAX1 ## ##

Immunohistochemistry expression of Human Herpes Virus-8 in cutaneous vascular lesions 2 2 Backgrounds: Kaposi sarcoma is a low-grade vascular tumor with the uniform expression of latent nuclear antigen-1 of the human herpes virus 8 (HHV-8). Differentiation of Kaposi sarcoma from other benign and malignant vascular or non-vascular spindle cell lesions is sometimes a manner of challenge. Thus, the expression of human herpes virus 8 in a fixed specimen would be diagnostically useful. This study aimed at immunohistochemical detection of human herpes virus-8 in cutaneous vascular lesions. Methods: This cross-sectional study was conducted on 46 cases of cutaneous vascular lesions including six cases of Kaposi Sarcoma, twenty-five cases of Pyogenic Granuloma, four cases of Angiolymphoid Hyperplasia with Eosinophilia, three cases of Masson Tumor, two cases of Arteriovenous Hemangioma, two cases of Sclerosing Hemangioma, three cases of Angiofibroma, and one case of Lymphangioma. After histologic confirmation, immunohistochemistry was done on sections of paraffin-embedded tissue with mouse anti-HHV-8 antibody. Results: Of 46 patients, 27 (58.7%) were male and 19 (41.3%) were female, and the mean age was 46.36±17.48 years. All 6 Kaposi sarcoma cases showed strong, nuclear staining for HHV-8 (100%). All 6 patients with HHV-8 positive results were older than 60 years. Sarcoma cases included four (66.7%) resection specimens from the soft tissues of the leg and two (33.3%) resection specimens from the soft tissues of the hand. Conclusions: The high sensitivity and specificity of the immunohistochemical method for detecting HHV-8 in skin lesions, especially Kaposi sarcoma, makes it a reliable and cost-effective tool to differentiate Kaposi sarcoma from other vascular and non-vascular spindle cell lesions. 172 177 2023/04/132023/04/72023/04/252023/04/82023/04/242023/04/202023/04/242023/03/11 1401/12/20 2023/06/242023/05/202023/05/172023/06/142023/06/112023/06/82023/06/182023/06/15 1402/3/25 Saeedeh Khakisahneh Saeedeh Khakisahneh Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran saeedekhaki@yahoo.com Maryam Hematti Maryam Hematti Clinical Research Development Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran maryam_hematti@yahoo.com Sedigheh Khazaei Sedigheh Khazaei Clinical Research Development Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran skhazaei2003@yahoo.com Mazaher Ramezani Mazaher Ramezani Molecular Pathology Research Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran mazaher_ramezani@yahoo.com Human Herpes Virus 8 Kaposi Sarcoma Cutaneous vascular lesions Immunohistochemically method. ## ##