Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 17 3 2025 10 1 Subcutaneous Hematoma as an Unusual Presentation of Chronic Myelogenous Leukemia following Bone Marrow Aspiration: A Case Report and Narrative Review 1 4 EN Pourya Mashategan Department of Pediatrics, School of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran. Hassan Abolghasemi Department of Pediatrics, School of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran. Mohammad Kazem Emami Meibodi Department of Orthopedics, School of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran. Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the BCR-ABL1 fusion gene, also known as the Philadelphia chromosome. Bleeding complications are uncommon in the chronic phase of CML due to preserved platelet function. However, rare cases of subcutaneous hematoma have been reported in association with factor XIII deficiency or other coagulopathies. We report the case of a 19-year-old adolescent diagnosed with CML who developed a subcutaneous hematoma after bone marrow aspiration. The patient presented with localized swelling and tenderness at the aspiration site, which was later confirmed as a hematoma on imaging. Laboratory tests revealed a preserved platelet count, but suggested a possible underlying coagulopathy. Further investigation revealed a factor XIII deficiency contributing to the unusual presentation. This case highlights the importance of considering rare bleeding disorders, such as factor XIII deficiency, in patients with CML who present with unusual bleeding manifestations. Early recognition and management of such complications are critical for optimal patient outcomes.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 17 3 2025 10 1 Detection of T315I Mutation in Ph+ Leukemias: Clinical Insights from One Case Report 5 13 EN Carolina Jaramillo Jaramillo School of Bacteriology, Colegio Mayor de Antioquia, Colombia. Juliana Pérez Mejía Health Sciences, Colegio Mayor de Antioquia, Colombia. Sara María Rave Zapata Antioquia, Colegio Mayor de Antioquia, Colombia. Maria Isabel Villa Palacio Faculty of Health Sciences, Colegio Mayor de Antioquia, Colombia. Diana Carolina Velasco Cardona Health Sciences, Colegio Mayor de Antioquia, Colombia. The reciprocal translocation between chromosomes 9 and 22, known as the Philadelphia chromosome, results in the formation of the BCR/ABL fusion gene. This genetic aberration leads to dysregulation of intracellular kinase activity. The detection of the Philadelphia chromosome is a critical component of the diagnostic evaluation of myeloproliferative neoplasms and acute lymphoid leukemia. In treatments involving tyrosine kinase inhibitors, at least 70 genetic variants have been documented as factors that induce resistance to drugs. This includes the T315I mutation, which has been identified as the most prevalent in multiple countries and is of significant clinical significance. This mutation is detected in patients who have experienced therapeutic failure, thereby significantly restricting the available treatment options. In Colombia, the prevalence of this mutation and the dynamics of its appearance are not yet fully understood. Furthermore, there is a paucity of information regarding the management and prognosis of patients who express the mutation. In this study, the genomic DNA of 26 patients with Philadelphia chromosome was analyzed using the real-time molecular technique PCR. The objective was to identify the T315I genetic variant, which was positive in two of the patients diagnosed with CML. We present a case of a 39-year-old female patient diagnosed with Ph+ CML who exhibited resistance to treatment and detection of this mutation.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 17 3 2025 10 1 Comparison of Cytochemistry and Flow Cytometry for Leukemia Immunophenotyping: A Systematic Review and Meta-Analysis 14 25 EN Ajay Kumar Department of General Medicine, Teerthanker Mahaveer Medical College & Research Centre,Teerthanker Mahaveer University, Moradabad, UP, India. Prithpal Singh Matreja Department of Pharmacy, Teerthanker Mahaveer Medical College & Research Centre, Teerthanker Mahaveer University, Moradabad, UP, India. Vinod Kumar Singh Department of General Medicine, Teerthanker Mahaveer Medical College & Research Centre,Teerthanker Mahaveer University, Moradabad, UP, India. Seema Awasthi Department of Pathology, Teerthanker Mahaveer Medical College & Research Centre,Teerthanker Mahaveer University, Moradabad, UP, India. Background: Accurate diagnosis and classification of leukemia are essential for effective treatment planning. Traditional cytochemistry relies on enzyme-based staining for morphological evaluation, while flow cytometry (FCM) employs monoclonal antibodies to detect multiple surface and intracellular markers. This systematic review and meta-analysis compared the diagnostic accuracy of cytochemistry and FCM in leukemia immunophenotyping. Methods: A systematic search of PubMed and Google Scholar was conducted according to PRISMA guidelines. Studies evaluating sensitivity, specificity, and accuracy of cytochemistry and FCM in diagnosing acute and chronic leukemia were included. Data extraction covered study characteristics, diagnostic markers, and performance outcomes. Meta-analysis was performed to compare diagnostic values across methods. Results: Eleven eligible studies comprising pediatric and adult leukemia cases were analyzed. Cytochemical stains such as Myeloperoxidase (MPO) and Sudan Black B (SBB) showed high specificity (91–100%) and moderate-to-high sensitivity (60–97%), while Periodic Acid–Schiff (PAS) and Nonspecific Esterase (NSE) had lower reliability. FCM demonstrated superior diagnostic performance with average sensitivity of 87.7% and specificity of 85.6%, achieving >95% accuracy in several studies. Marker panels including CD3, CD45, CD79a, and MPO enabled precise subtype differentiation and minimal residual disease (MRD) detection. Conclusion: Cytochemistry remains useful as an affordable screening tool in resource-limited settings, but FCM provides greater sensitivity, specificity, and comprehensive immunophenotypic data, making it the preferred method for leukemia diagnosis and monitoring. Combining both approaches can enhance diagnostic performance across diverse clinical contexts.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 17 3 2025 10 1 Chemokine-guided Stem Cell Migration for Retinal Regeneration: A Systematic Review 26 34 EN Ashish Chander Teerthanker Mahaveer University, Teerthanker Mahaveer Medical College & Research Centre (TMMC & RC), Moradabad, Uttar Pradesh, India. Vinod Kumar Singh Teerthanker Mahaveer University, Teerthanker Mahaveer Medical College & Research Centre (TMMC & RC), Moradabad, Uttar Pradesh, India. Sonika Sharma Teerthanker Mahaveer University, Teerthanker Mahaveer Medical College & Research Centre (TMMC & RC), Moradabad, Uttar Pradesh, India. Prithpal Singh Matreja Teerthanker Mahaveer University, Teerthanker Mahaveer Medical College & Research Centre (TMMC & RC), Moradabad, Uttar Pradesh, India. Background: Retinal degeneration remains one of the predominant causes of blindness, with extremely low regenerative capacity in the mammalian retina. Stem cell-based therapy is a highly promising approach for retinal regeneration, but efficient stem cell migration and integration are significant challenges. This systematic review aimed to discuss chemokine-directed stem cell migration in retinal regeneration, summarising important chemokines, signalling pathways, and therapeutic opportunities. Methods: A systematic literature search was done in PubMed, Embase, Scopus, Web of Science, Cochrane Library, CINAHL, and PsycINFO between January 2010 and January 2025. Preclinical and clinical studies that explored chemokine-stimulated stem cell migration during retinal repair were included based on the inclusion criteria. The data extracted included chemokine-receptor interaction, signalling pathways, type of stem cells, route of delivery, and outcomes of retinal repair. The ROBINS-I tool was used to evaluate the risk of bias. Results: In 384 studies, 12 were included. The SDF-1/CXCL12-CXCR4 pathway was explored in the most detail, augmenting stem cell homing and integration. Other pathways, such as ERK/MAPK, PI3K/Akt, and JAK-STAT, also played a role in migration and survival. Chemokine-modulated therapies enhanced retinal function and repair, but immune responses and delivery issues remain. New approaches such as biodegradable scaffolds, magnetic targeting, and chemically engineered chemokines were discovered to optimise stem cell localisation and efficacy. Conclusion: Chemokine-directed stem cell migration is an exciting field for retinal regeneration, which has the potential to improve targeted cell delivery and integration. While SDF-1/CXCL12 remains the gold standard, other pathways and new delivery pathways are also extremely capable. Augmenting chemokine-based therapies, overcoming immunological barriers, and translating them into the clinic in the future will be paramount to optimising stem cell-mediated retinal repair.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 17 3 2025 10 1 Effects of Metformin on Leukemia: Biological Mechanisms, Targets, and Treatment Possibilities 35 45 EN Parisa Dana Islamic Azad University،Science and Research Branch, Tehran, Iran. Abdolkhalegh Deezagi National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. Metformin is a widely prescribed medication for managing diabetes, but it also affects cancer cell metabolism through both direct and indirect mechanisms. Cancer cells often divide rapidly, and this quick division, along with metabolic changes, increases intracellular free radicals and inhibits the enzyme hexokinase. This inhibition prevents the conversion of glucose to glucose-6-phosphate, leading to glucose deprivation and subsequently causing mitochondrial depolarization and apoptosis in cancer cells. KDM1A is an epigenetic regulator that plays a vital role in cancer development. Both KDM1A and metformin influence autophagy and cancer-related pathways, and their interaction could lead to new treatment strategies. Metformin reduces oxidative stress and activates ATM signaling, since the ATM gene encodes a tumor suppressor protein that helps repair DNA mutations during stress. Additionally, the drug enhances the recognition of damaged DNA by increasing ATM protein levels. In acute myeloid leukemia (AML), leukemic stem cells (LSCs) often develop resistance after chemotherapy, which greatly contributes to treatment failures. This article aims to explore how metformin affects LSCs, DNA repair gene expression, and related biological mechanisms, as well as its targets and therapeutic potential. This study reviews existing articles about metformin's mechanisms in leukemia. Metformin shows significant potential for reducing mortality rates associated with various cancers, including leukemia.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 17 3 2025 10 1 The Role of Artificial Intelligence in Shaping the Future of Hematological Diagnosis and Treatment 46 61 EN Zahra Haghshenas School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Hassan Shokri Garjan Department of Medical Informatics, School of Allied Medical Science, Urmia University of Medical Science, Urmia, Iran. Atefeh Moghassem Laboratory Hematology and Blood Bank Department, School of Allied Medical Science, Shahid Beheshti University of Medical Science, Tehran, Iran. Pooya Vahedi School of Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran. Yasmin Tabatabavakili School of Nursing and Midwifery, Shahid Beheshti University of Medical Science, Tehran, Iran. Diana Hosseinzadeh Third faculty of medicine, Charles University, Prague, Czech Republic. Goli Asgari Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Elham Nazari Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Tahmine Aldaghi Institute of Biophysics and Informatics, First Faculty of Medicine, Charles University, Prague, Czech Republic Hematological disorders continue to pose significant challenges in clinical practice due to their complexity and potential for severe outcomes. This review provides a comprehensive overview of the role of Artificial Intelligence (AI) in enhancing the diagnosis and treatment of these conditions. Drawing on 177 studies published between 2012 and 2025 from PubMed and Google Scholar, the review examines fundamental concepts of AI and machine learning, their applications in diagnostic and therapeutic processes, and the challenges and limitations associated with their clinical implementation. The findings highlight the potential of AI to improve diagnostic accuracy, optimize treatment strategies, and support decision-making in hematology. By synthesizing current knowledge, this study underscores the importance of integrating AI into research and clinical practice and offers insights into future directions for advancing patient care in hematological disorders.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 17 3 2025 10 1 Comparative Evaluation of Custom Convolutional Neural Networks and EfficientNet-B3 for Malaria Cell Image Classification: Impact of Targeted Data Augmentation on Model Performance 62 72 EN Reza Mohit Department of Anesthesia, School of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran Emad Milani Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Ata Amini Department of Health Information Management and Medical Informatics, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran Mehrnaz Ahani Department of Midwifery, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran Elham Nazari Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Tahmineh Aldaghi Institute of Biophysics and Informatics, First Faculty of Medicine, Charles University, Prague, Czech Republic. Background: Malaria diagnosis with thin blood smears remains labor-intensive and relies on the operator. Deep learning could enable accurate automation. Objective: Compare four convolutional approaches for classifying parasitized versus uninfected erythrocytes and to evaluate whether targeted image-quality augmentations enhance performance. Materials and Methods: We used the balanced NIH/Kaggle dataset, which included 13,780 parasitized and 13,780 uninfected samples. Data were split stratified into training, validation, and test sets (70/15/15). Images were resized to 256×256 and normalized. Four experiments were conducted: (1) a custom CNN; (2) the same CNN with targeted augmentation applied to 20% of training samples per class—using Contrast Limited Adaptive Histogram Equalization [CLAHE] and controlled brightness adjustment—and augmented images were added back to the training set (totaling 30,864 images); (3) a soft-attention parallel CNN (SPCNN); and (4) transfer learning with EfficientNet-B3 on 300×300 inputs with full fine-tuning. Evaluation metrics included accuracy, precision, recall, F1 score, and AUC-ROC. Results: EfficientNet-B3 achieved the highest performance with a validation accuracy of 0.9741, 98% precision, 96% recall, an F1 score of 0.97, and an AUC-ROC of 0.9964. SPCNN was competitive but slightly lower, with a validation accuracy of 0.9652, 98% precision, 95% recall, an F1 score of 0.96, and an AUC-ROC of 0.9909. The baseline CNN had a validation accuracy of 0.9649, 97% precision, 94% recall, an F1 score of 0.96, and an AUC-ROC of 0.9910. Targeted augmentation resulted in negligible change compared to the baseline CNN, with a validation accuracy of 0.9647, an F1 score of 0.96, and an AUC-ROC of 0.9908, indicating limited added discriminative value for this dataset. Conclusion: EfficientNet-B3 outperformed SPCNN and custom CNNs. The CLAHE/brightness strategy applied to 20% of training images and added back to the dataset did not significantly improve generalization. External validation and prospective field testing are necessary before clinical deployment.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 17 3 2025 10 1 Assessment of Lysosome-Associated Membrane Protein (LAMP5) in Newly Diagnosed Multiple Myeloma Patients and Correlation to Clinical Outcome 73 78 EN Nahed Moawad Ibrahim Rakha Department of Internal Medicine and Clinical Hematology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Amal Elaffifi Department of Internal Medicine and Clinical Hematology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Rana Abbas Department of Internal Medicine and Clinical Hematology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Ghada Mged Department of clinical pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Shrouk Salah Department of Internal Medicine and Clinical Hematology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Haydi Sayed Department of Internal Medicine and Clinical Hematology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Introduction: Lysosome-associated membrane protein 5(LAMP5) is one of the glycosylated proteins which are implicated in several different features of cell biology and can impact cellular processes for instance phagocytosis, autophagy, lipid transference, and aging. Interestingly, it has a significant role in cancer progression, metastatic spread and aggressiveness. It has been reported to be significantly expressed in many hematopoietic malignancies as leukemias and Multiple Myeloma (MM). Objectives: This study used enzyme-linked immunosorbent assay (ELISA) to measure the level of LAMP5 in newly diagnosed MM patients, and the level was correlated to the clinical outcome of the patient. Methods: A prospective study was done on 64 people, including 32 newly diagnosed MM patients and 32 age- and gender-matched healthy controls. ELISA was used to assess the levels of LAMP5 in serum samples. Clinical data and LAMP5 expression correlations were assessed. Results: MM patients’ LAMP5 levels were found to be statistically significantly higher than those of healthy controls (P<0.0001), However, LAMP5 does not correlate with clinical outcomes, laboratory results, or patient clinical data. Conclusion: This report emphasizes that LAMP5 expression in newly diagnosed multiple myeloma patients was highly significant by ELISA and its influence on patient’s prognosis still unclear as there was no significant correlation with other clinical data, which indicates more research on large scale of patients to determine its significance of its expression on prognosis.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 17 3 2025 10 1 The Immune Microenvironment in Acute Myeloid Leukemia: Mechanisms of Immune Evasion and Emerging Therapeutic Strategies 79 95 EN Vinod Kumar Singh Department of General Medicine, Teerthanker Mahaveer Medical College & Research Centre, Teerthanker Mahaveer University, Moradabad, Uttar Pradesh, India. Prithpal Singh Matreja Department of Pharmacology, Teerthanker Mahaveer Medical College & Research Centre, Teerthanker Mahaveer University, Moradabad, Uttar Pradesh, India. Sudhir Singh Department of microbiology, Teerthanker Mahaveer Medical College & Research Centre, Teerthanker Mahaveer University, Moradabad, Uttar Pradesh, India. Seema Awasthi Department of pathology, Teerthanker Mahaveer Medical College & Research Centre, Teerthanker Mahaveer University, Moradabad, Uttar Pradesh, India. Acute Myeloid Leukemia (AML), a diverse type of blood cancer, is characterized by the unchecked multiplication of myeloid precursor cells within a disrupted bone marrow microenvironment (BMM). Leukemic blasts alter the BMM to create a leukemia niche, promoting immunological evasion and disease development. High relapse rates highlight the need for novel therapeutic approaches, even if chemotherapy is still the cornerstone of treatment. AML cells use many strategies to avoid immune identification, such as suppressing anti-leukemic immune responses and upregulating immune checkpoints. Immunotherapies like checkpoint inhibitors that target these pathways have shown encouraging promise. The intricate relationships between AML and the immunological milieu are examined in this review, with a focus on immune evasion, treatment resistance, and innovative immunotherapeutic strategies to improve anti-leukemic immunity.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 17 3 2025 10 1 Efficacy and Challenges of Pediatric Cord Blood Transplantation: Insights from a Retrospective Single-Center Study 96 105 EN Bibi Shahin Shamsian Pediatric Congenital Hematologic Disorders Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran Nader Momtazmanesh Pediatric Congenital Hematologic Disorders Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran Vahide Zeinali Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran Arezou Sayad Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran sharareh kamfar Pediatric Congenital Hematologic Disorders Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Background: Umbilical cord blood transplantation (UCBT) serves as a valuable alternative for pediatric patients without matched donors, particularly in urgent situations where timely transplantation is critical. While UCBT offers immunological benefits and broader donor availability, its clinical outcomes remain inconsistent, especially in non-malignant hematologic disorders. Objective: To evaluate clinical outcomes of UCBT in pediatric patients with malignant and non-malignant hematologic conditions, focusing on transplant-related complications and survival rates. Methods: In this retrospective single-center study, we analyzed 14 pediatric patients (aged 0.7–11 years) who underwent allogeneic UCBT at Mofid Children’s Hospital between 2019 and 2024. Data were extracted from institutional registries and medical records, including patient demographics, disease classification, graft characteristics, conditioning regimens, engraftment status, incidence of graft-versus-host disease (GVHD), infections, and survival outcomes. Results: Among the 14 patients, 85.7% had non-malignant disorders. Most received unrelated donor grafts, with HLA matching of 6/6 in 42.9%, 5/6 in 50%, and 4/6 in 7.1%. The median total nucleated cell dose was 4.95×10⁷/kg, and the median CD34⁺ cell dose was 1.7×10⁵/kg. Neutrophil engraftment was achieved in 42.9% of patients, with a median of 19 days. Primary graft failure occurred in 50% of patients, and secondary graft failure in 7.1%. Acute GVHD developed in 14.3% of cases, while no chronic GVHD was observed. CMV reactivation occurred in 42.9% of patients, and bacterial infections were reported in 57.1%. The overall survival rate was 42.9%, with transplant-related mortality accounting for 57.1% of cases, due to infections and graft failure. Conclusion: UCBT remains a feasible therapeutic option for pediatric patients lacking matched donors, particularly in urgent or resource-constrained settings. However, the high incidence of graft failure and infection-related mortality highlights the need for improved graft selection strategies, personalized conditioning protocols, and optimized post-transplant care to enhance patient outcomes.