Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 16 2 2024 6 1 BCR-ABL positive T cell Acute Lymphoblastic Leukemia (T-ALL): Exploring A Rare Case with A Comprehensive Review 1 6 EN Setare Kheyrandish Student Research Committee, Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Shiva Shadani Clinical Research Development Center of Aliasghar Hospital, Iran University of Medical Sciences, Tehran, Iran. Aziz Eghbali Clinical Research Development Center of Aliasghar Hospital, Iran University of Medical Sciences, Tehran, Iran. Behzad Poopak Department Of Medical Laboratory Sciences, Faculty of Paramedical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. Davood Bashash Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. CD4+/CD8+ double-positive (DP) thymocytes are normal cells within the thymus. However, the presence of mature DP T cells is indicative of cancer and abnormality in peripheral blood. Philadelphia+ (Ph+) T-ALL is extremely rare, but it holds significant therapeutic and prognostic implications. The incidence and outcomes of BCR-ABL+ T-ALL remain uncertain, and distinguishing it from T-cell lymphoblastic crises of CML can be challenging. The current document discussed a rare case of CD4+/CD8+ BCR-ABL+ T-ALL in an 11-year-old Iranian male, detailing his medical conditions, laboratory findings, and treatment. The patient presented with enlarged lymph nodes, splenomegaly, anemia, leukocytosis, and severe thrombocytopenia. The blood smear was nearly filled with irregular/convoluted and cleaved nuclear blasts with fine chromatin. The patient received imatinib with induction chemotherapy. After two months, the patient achieved complete remission with undetectable Minimal/Measurable Residual Disease (MRD). By detailing the patient's characteristics and the required tests, the manuscript contributes to a deeper understanding of this complex disease subtype. Furthermore, by examining and comparing the current case with other available cases, the study lays the groundwork for better characterizing the disease and developing more effective therapeutic strategies.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 16 2 2024 6 1 Categorized Serum miRNAs as Potential Biomarkers for Predicting the Progression and Prognosis of Colorectal Cancer 7 14 EN Meral Merve Oğuz Department of Internal Medicine, Pamukkale University, Denizli, Turkey/ The Affiliated Hospital of Pamukkale University. Ehteram Khademi Siahestalkhi Department of Medical Genetics, Faculty of Medicine, Pamukkale University, Denizli, Turkey. Arzu Yaren Department of Internal Medicine, Pamukkale University, Denizli, Turkey/ The Affiliated Hospital of Pamukkale University. Aydin Demiray Department of Medical Genetics, Faculty of Medicine, Pamukkale University, Denizli, Turkey. Atike Gökçen Demiray Department of Internal Medicine, Pamukkale University, Denizli, Turkey/ The Affiliated Hospital of Pamukkale University. Background: Colorectal cancer (CRC), a common and aggressive gastrointestinal cancer, presents significant challenges in diagnosis and prognosis prediction despite available detection and treatment options. Many studies emphasized the crucial link between abnormal microRNA regulation and their potential role in cancer development and progression. These miRNAs are recognized as important non-invasive biomarkers for prognosis and overall survival prediction in various cancers, including CRC. Materials and Methods: In this study, we compared the expression patterns of eight miRNAs in the serum of 36 CRC patients with those of 37 healthy controls. The matching criteria included clinicodemographic factors and CRC susceptibility, and the analysis was performed using quantitative real-time PCR (qRT-PCR). Results: The serum miRNA levels of these eight miRNAs (miR-19a, miR-92a, miR-103, miR-106a, miR-107a, miR-150, miR-221, and miR-720) in the study groups are significantly higher compared to the control group. This analysis revealed eight specific miRNAs with varying expression levels in CRC patients.  Furthermore, bioinformatic analysis using data collection and analytical tools has shown that these miRNAs may be associated with important aspects of colorectal cancer development and progression through the PI3K/AKT/PTEN, WNT/CATENIN, and EMT signaling pathways.Conclusion: Our analysis has identified a group of 8 overexpressed miRNAs (miR-19a, miR-92a, miR-103, miR-106a, miR-107a, miR-150, miR-221, and miR-720.) in serum samples of CRC patients. : Although further validation in larger and more diverse groups is necessary,  these findings support a potential mechanism of action for these miRNAs in CRC and their association with essential signaling pathways, including PI3K/AKT/PTEN, WNT/CATENIN, and EMT.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 16 2 2024 6 1 Evaluating Adverse Events in COVID-19 Recovered Convalescent Plasma Donors: A Comprehensive Analysis 15 23 EN Shalini Bahadur Department of Pathology, Government Institute of Medical Sciences, Greater Noida Bhumika Gupta Department of Pathology, Government Institute of Medical Sciences, Greater Noida Shalini Shukla Department of Pathology, Government Institute of Medical Sciences, Greater Noida Paridhi - Department of Pathology, Government Institute of Medical Sciences, Greater Noida Shivani Kalhan Department of Pathology, Government Institute of Medical Sciences, Greater Noida Madhuvan Gupta Department of Pathology, Government Institute of Medical Sciences, Greater Noida Background: The emergence of the COVID-19 pandemic prompted the exploration of convalescent plasma therapy (CPT) as a potential treatment modality. This study provides a comprehensive understanding of adverse events in COVID-19-recovered convalescent plasma (CP) donors for optimizing donor safety and refining donation protocols. The aim is to quantify the type and severity of adverse events associated with CP donation. Materials and Methods: The present one-year retrospective study was undertaken in the blood center of a tertiary care hospital of Western Uttar Pradesh that was a multicentric site in the ICMR Placid trial and a dedicated COVID hospital during the first and second wave in India. Data was analyzed from donor adverse events (DARs) captured during the study period and evaluated for different parameters namely age, gender, body weight, donor status (first-time donor or previous donor), body mass index, blood volume processed, plasma volume collected and lag time between negative RT-PCR report and plasmapheresis. To determine the significance of variations in rates of DARs, Chi-square test was performed (p-value <0.05 considered significant). Results: A total of 769 donations were performed in the study duration. The maximum donors were between the age group of 26-33 years with 301 donations were from this age group.  Out of 769 donations, 648 donors (84.3%) showed no DARs, while 121 donors (15.7%) experienced adverse reactions. Conclusion: Our findings provide essential insights into donor safety, hoping to support and plan future pandemic response strategies against novel infectious diseases.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 16 2 2024 6 1 High Variability in HLA-DRB1*03, a Predisposing Allele in Acute Lymphoblastic Leukemia 24 33 EN Norfarazieda Hassan UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia Siti Zuleha Idris Department of Pathology, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia Kian Meng Chang Department of Hematology, Hospital Ampang, Clinical Hematology Laboratory, Jalan Mewah Utara, Pandan Mewah, Ampang, Selangor 68000, Malaysia Raudhawati Osman Hematology Unit, Hospital Kuala Lumpur, Jalan Pahang, 50586 Wilayah, Persekutuan Kuala Lumpur, Malaysia Hishamshah Mohd Ibrahim Pediatric Department, Hospital Kuala Lumpur, 50586 Wilayah, Persekutuan Kuala Lumpur, Malaysia Jasbir Singh Dhaliwal Allergy and Immunology Research Centre, Institute for Medical Research, 50588 Jalan Pahang, Kuala Lumpur Maha Abdullah Department of Pathology, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia Acute lymphoblastic leukemia (ALL) remains a significant health concern, particularly in children, with genetic predisposition playing a crucial role in its etiology. Among the predisposing HLA Class II alleles, —DRB1*03 has emerged as a notable candidate associated with increased susceptibility to ALL. This study aims to investigate the extent of variability within the HLA-DRB1 alleles as genetic biomarkers and its implications in ALL pathogenesis. Through methods of polymerase chain reaction—sequence-specific oligonucleotides (PCR-SSO) and sequence-based typing (SBT) analysis, our data revealed HLA-DRB1*16 as another genetic risk and HLA-DRB1*07 and HLA-DRB1*12 alleles as protective alleles in ALL patients. Further sequencing demonstrates a remarkable diversity in the HLA-DRB1*03 allele in ALL patients but none among the HLA-DRB1*16 alleles compared to normal samples. Our findings confirmed the association of HLA-DRB1 alleles with ALL and shed light on SNPs or mutations in the risk alleles. Genetic variability in HLA-DRB1 alleles is a significant factor to consider in improving outcomes in immunotherapy.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 16 2 2024 6 1 Optimizing Patient Blood Management in Cardiac Surgery: A Systematic Review 34 50 EN Sultan Ghazzay Alotaibi Cardiac Center, King Fahd Armed Forces Hospital, Ministry of Defense, Jeddah, Saudi Arabia. Muneeb Ammar Alnouri Cardiac Center, King Fahd Armed Forces Hospital, Ministry of Defense, Jeddah, Saudi Arabia. Rawaa Mahmoud Sulaiman Family Medicine Department, Dr. Sulaiman Fakeeh Hospital, Jeddah, Saudi Arabia Abdulkhalek Abduljaleel King Fahad General Hospital, Jeddah, Saudi Arabia. Ahmed Foad Bogari King Fahad General Hospital, Jeddah, Saudi Arabia. Hani Nabeel Mufti King Faisal Cardiac Center, King Abdul-Aziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Saudi Arabia Background: Heart diseases are typically treated with cardiac surgery, which often requires preoperative, intraoperative, and postoperative blood transfusion. However, blood transfusion is a risk factor for serious complications after cardiac surgery, including death. Patient Blood Management (PBM) programs were developed to mitigate the risks of blood transfusion by reducing its use in cardiac surgery. Objective: This systematic review aims to study the currently published literature on PBM strategies that effectively reduce the rates of preoperative, intraoperative, and postoperative blood transfusion for cardiac surgery. Methodology: This systematic review analyzed preoperative blood management strategies in cardiac surgery, focusing on studies published between 2018 and 2024 designed to reduce blood transfusion rates. The study utilized a modified 2022 protocol for systematic reviews and meta-analysis, grading evidence using a 2008 system, and selected 21 studies for a systematic review. Results: The studies identified 12 PBM strategies, including iron therapy, Aminocaproic acid, Cardiopulmonary by-pass system, cell salvage, Perfusion Blood Collection, gel foam patches, Large-volume acute normovolemic hemodilution, Platelets Transfusion Therapy, Modified Ultrafiltration, TEM-based algorithms, and restrictive management of SVO2, which significantly reduced blood transfusion volumes and rates before, during, and after cardiac surgery. Conclusion: The 12 PBM strategies identified are valuable additions to the current list, but further clinical evaluation is needed to improve their efficacy and safety in cardiac surgery.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 16 2 2024 6 1 Evaluation of the Home Safety and Child-friendly Environment for Children with Bleeding Tendency Disorders 51 59 EN Fereshteh Karbasian Department of pediatric gastroenterology and hepatology, Iran University of Medical Sciences, Tehran, Iran. Maral Nikfarjam Department of Pediatric, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Kiarash Noorizadeh Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Ali Abbasi-Kashkooli Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Peyman Eshghi Pediatric Congenital Hematologic Disorders, Research Institute for Children Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran Hamid Reihani Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Background: This study aims to assess the safety level of the different home parts for children with a bleeding tendency disorder (especially hemophilia) and identify the elements that affect this safety. Materials and methods: We conducted a cross-sectional study on the children referred to the Mofid Children’s Hospital from the beginning of 2018 to the end of 2020. Information was gathered via a checklist. Inclusion criteria were children between 1 to 5 years old with bleeding tendencies, and exclusion criteria were the presence of other disorders. The safety was measured in five areas at home: 1- physical conditions 2- kitchen 3- bathroom 4- toys 5- first aid equipment and essential phone numbers. Results: Forty-one children participated in this study which 31 (75.61 %) were boys. Eleven (28.95 %) children experienced zero accidents at home and eight (21.05 %) children experienced more than three accidents at home. The Mean and 95% confidence interval scores were 7.97 (7.37-8.57) for the physical condition section, 8.22 (7.73-8.70) for the kitchen section, 8.15 (7.66-8.65) for the bathroom section, 7.93 (7.15-8.71) for the toys section, and 7.30 (6.60-8.01) for the first aid equipment and essential phone numbers section. The physical condition safety score was significantly higher in families whose fathers had a college education than in fathers with secondary and diploma education (P-value = 0.024). The kitchen section safety score was significantly higher in families where the father has a freelance job than the employee or worker (P-value = 0.040). Conclusion: The mother’s age, father’s educational level, and father’s job are the factors that affect the level of safety significantly. Providing toys that are age-appropriate and safe (without separable parts or holes) could be an important point for parents with children with bleeding disorders.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 16 2 2024 6 1 Type 2N von Willebrand Disease: Overcoming Diagnostic Challenges for Accurate Diagnosis 60 69 EN Behnam Azari Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine Minoo Ahmadinejad Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine Von Willebrand Factor (vWF) defects can cause von Willebrand Disease (vWD), which is known to be the most prevalent inherited bleeding disorder worldwide. According to the latest classifications, vWD is categorized into three main types. Types 1 and 3 are quantitative defects, while type 2 vWD is caused by qualitative abnormalities in vWF. Furthermore, ISTH classifies type 2 vWD is into four subtypes known as 2A, 2B, 2N, and 2M. Type 2N vWD is an uncommon type of vWD that is inherited in an autosomal recessive pattern. In this type, the binding capacity of vWF to Factor VIII (FVIII) is reduced, resulting in FVIII's shortened half-life in the patient's plasma. Due to the pathophysiology of Type 2N vWD, affected individuals exhibit signs and symptoms similar to those with mild to moderate hemophilia A. These symptoms include mucocutaneous bleeding or bleeding following trauma or surgery. Furthermore, the primary laboratory findings of affected individuals are comparable to those of hemophilia A patients, with Factor VIII levels ranging from 1 to 40 U/dL. It is crucial to differentiate these disorders for optimal treatment and accurate genetic counseling. Physicians may use a combination of clinical assessment, family history, bleeding scores, and laboratory tests to differentiate between the two disorders. Further genetic testing may be necessary to confirm the diagnosis and assess the risk of inheritance. This review outlines methods for diagnosing type 2N vWD and distinguishing it from hemophilia A, based on published papers and current guidelines.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 16 2 2024 6 1 Molecular Pathways of Gliomas Involving RNA-Binding Protein Dynamics 70 83 EN Saman Batool Gomal Centre of Biochemistry and Biotechnology, Gomal University, D.I.Khan, Pakistan. Hamza Tanveer Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan Faisal Naeem Department OF Forensic Medicine and Toxicology, Post Graduate Medical Institute, Lahore, Pakistan Asma Sarfaraz Shifa Tameer-e-Millat University of Pharmaceutical Sciences, Islamabad, Pakistan Gliomas are malignant brain tumors with complicated molecular changes contributing to their aggressiveness and limited treatment choices. RNA-binding proteins are important in post-transcriptional regulation, altering gene expression and impacting glioma formation. In this review article, we will deliberate different molecular pathways of gliomas in which RNA-binding proteins are involved. Studies reveal that a few years ago, RNA-binding proteins had a causative effect on various cancer types such as leukemia, glioblastoma, intestinal, renal, etc. RNA-binding proteins have surfaced as key players in regulating post-transcriptional processes. So, we will discuss in this article Maintaining Glioma Cells Growth, RNA-binding proteins mutations, interacting with deubiquitinating enzymes, RBP Methylation Activates Oncogenic Pathways and RNA-binding proteins in glioma subtypes, highlighting their role in tumorigenesis, invasion, angiogenesis, and therapeutic resistance.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 16 2 2024 6 1 Investigating the Dynamic Interplay Between Cellular Immunity and Tumor Cells in the Fight Against Cancer: An Updated Comprehensive Review 84 101 EN Seyed Ali Aghapour Neonatal & Children᾿s Health Research Center, Golestan University of Medical Sciences, Gorgan, Iran. Mehdi Torabizadeh Abuzar Children’s Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Seyed Sobhan Bahreiny Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Najmaldin Saki Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Mohammad Ali Jalali Far Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Arshid Yousefi-Avarvand Department of Laboratory Sciences, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Kiana Dost Mohammad Ghasemi Department of Medical Sciences, Lahijan Azad University of Medical Sciences, Lahijan, Gilan, Iran Mojtaba Aghaei Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Mohammad Mehdi Abolhasani Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Mohammad Sharif Sharifani School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Ehsan Sarbazjoda Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Moslem Javidan Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran The dynamic interplay between cellular immunity and tumor cells is essential in cancer advancement and response to therapy. This updated, comprehensive review examines the intricate relationship between these components, focusing on the function of different subsets of immune cells in both innate and acquired immunity. A literature search was conducted to identify cytokines involved in tumor cell induction, using keywords such as cytokines, tumor cells, immune cells, and cancer. Relevant articles published between 2003 and 2024 were reviewed, and their data were summarized. The review highlights the different roles of immune cell subsets in coordinating immune responses against tumors. Tumor-associated macrophages (TAMs) And Myeloid-derived suppressor cells (MDSCs) often stimulate cancer growth and evasion of the immune system by suppressing effector cells. Eosinophils and natural killer (NK) cells contribute to tumor surveillance and cytotoxicity, while dendritic cells (DCs) recreate paramount function in T-cell activation and antigen presentation. The complement system and neutrophils contribute to immune regulation and tumor-associated inflammation. T lymphocytes, particularly antigen-presenting cells (APCs) and cytotoxic CD8+ T cells are central to acquired immunity and the anti-tumor immune response. This review highlights how cytokines interact with tumor cells and their role in cancer biology, paving the way for identifying improved prognostic and diagnostic factors. The compiled findings discuss valuable cytokines for a more effective diagnosis of tumors and an accurate prognosis prediction.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 16 2 2024 6 1 Impact of Low-Dose Alendronate Therapy on Target Joints in Hemophilia Patients in a Low-Income Country 102 110 EN Babak Abdolkarimi Lorestan University of Medical Sciences, Khorramabad, Iran Javad Rostami Lorestan University of Medical Sciences, Khorramabad, Iran Fatemeh Varehzardi Lorestan University of Medical Sciences, Khorramabad, Iran Shadi Tabibian Iranian Comprehensive Hemophilia Care Center, Tehran, Iran Niki Panahi Health service management, Science and Research branch, Islamic Azad University,Tehran, Iran Background: Osteoporosis poses a significant clinical challenge for patients with hemophilia (PWH), primarily due to repeated intra-articular bleeding and joint inflammation. The objective of this study was to assess the impact of a combination of calcium-vitamin D and alendronate tablets on reducing the frequency of hemarthrosis in PWH in Lorestan province. Methods: This non-randomized controlled trial involved a total of 118 PWH, out of which 55 patients with severe hemophilia A and B. Each patient underwent two assessments including the frequency and duration of bleeding episodes, and improvement in chronic joint pain, before and after receiving a combination of calcium-vitamin D, alendronate, tranexamic acid, and capsaicin ointment. Variables were measured at six-month intervals (at the beginning and end of the study). The statistical software used was SPSS version 21. Results: The average age of the patients was 33.99 ± 10.67 years. The average number of target joints was 4.18 ± 0.88. A significant correlation was observed between the number of bleeding episodes before and after medication intake (p <0.0001). Similarly, a correlation was found between pre- and post-medication atrophy around the target joint in PWH (p <0.0001). However, no association was detected between joint ankylosis before and after drug administration (p = 0.5). Importantly, there was an improvement in chronic pain post-medication (p <0.0001). Conclusion: The findings suggest that the combination of calcium-vitamin D and low-dose intermittent alendronate can improve hemophilia joint condition.