Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 14 3 2022 9 1 The protective role of deferoxamine in the prevention of doxorubicin-induced hepatic fibrosis in children: A randomized controlled clinical trial 1 10 EN Mohammadreza Bordbar Hematology Research center, Shiraz University of Medical Sciences, Shiraz, Iran Gholamreza Fathpour Hematology Research center, Shiraz University of Medical Sciences, Shiraz, Iran Seyed Mohsen Dehghani Medical sciences Sezaneh Haghpanah Shiraz Uni Hossein Molavi Vardanjani Shiraz Uni Mohammadreza Fattahi Shiraz uni Mahdi Shahriari shiraz uni Nader Shakibazad shiraz uni Background: This study aimed to investigate the protective role of deferoxamine (DFO) in the prevention of doxorubicin (DOX)-induced hepatic fibrosis in children. Methods: In this prospective randomized controlled trial, 61 treatment-naïve children (2-18 years) with different types of cancer who referred to a tertiary teaching hospital in the South of Iran were enrolled. They were randomly assigned to 3 groups; group 1 (control, n=21), group 2 (DFO 10 times DOX dose, n=20), group 3 (DFO 50mg/kg, n=20). DFO was administered as an 8-hour continuous intravenous infusion during and after DOX infusion in each chemotherapy cycle. Non-invasive serum markers of liver fibrosis, including AST-to-platelet ratio index (APRI), Fibrosis-4 (FIB-4) score and Fibro Test were measured in each individual. Besides, hepatic Fibro Scan was used after the last course of chemotherapy to estimate the fibrosis degree. Results: Alanine aminotransferase was mildly increased after treatment compared to before treatment. The treatment with DFO 10 times DOX dose was associated with a significant decline in post-treatment APRI (adjusted odds ratio 0.17; 95% confidence interval 0.03- 0.84. P-value=0.015). The METAVIR fibro scores were in the F0-F1 zone in all participants, and the results were comparable in study groups. No adverse drug effects were reported in the treatment groups. Conclusion: DOX may not lead to severe liver fibrosis if the maximum cumulative dose allowed is not exceeded. DFO at the dose of 10 times of DOX dose may have a potential protective role against liver fibrosis. More studies with longer follow-up are needed to further assess this issue.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 14 3 2022 9 1 Evaluation of the prognostic value of CD117 and CK20 biomarkers in urinary bladder carcinoma 11 15 EN Mahdieh Hamidfar Payam Noor Uni Elnaz Sheikhpour Hematology and Oncology Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Mahmood Akhavan Tafti shahid sadoughi uni Fateme Daneshmand Payam Noor Uni Mehdi Abedinzadeh Shahid Sadoughi University Background: Over-expression of CD117 and cytokeratin 20 (CK20) is seen in many malignancies. Given that few studies have been conducted regarding the role of these biomarkers in the etiology of bladder tumours, this study aimed to evaluate the prognostic value of CD117 and CK 20 biomarkers in the benign and malignant tumours of urinary bladder carcinoma. Methods: This case-control study was conducted on 62 bladder tumours (17 benign tumours and 45 malignant tumours). The immunohistochemistry technique was used to assess CK20 and CD117 biomarkers in tumour samples. Results: There is no significant difference between benign and malignant groups in terms of CD117 (p=0.094). No significant difference was observed between expression of CD117 in terms of grade (p=0.184). However, a significant difference was observed between benign and malignant groups in terms of CK20 expression (p=0.022). Moreover, a significant difference was observed between CK20 expression in terms of grade (p=0.009). In addition, a significant difference was observed between the age of patients considering grade (p<0.047). Conclusion: The results of the current study supported the role of CK20 in the carcinogenesis of urinary bladder carcinoma. Moreover, it seems that CK20 expression may be considered as a poor prognostic parameter in transitional bladder carcinoma. Furthermore, these findings indicated that patients with higher age had higher grade. In addition, assessment of CD117 expression did not play a main role in tumour progression. Therefore, it is not recommended for bladder tumours.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 14 3 2022 9 1 CD38 gene polymorphisms and genetic susceptibility to chronic lymphocytic leukemia 16 21 EN Morteza Hashemi Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Baqiyatallah University of Medical Sciences, Tehran, Iran. Hadi Esmaeili gouvarchin ghaleh Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Baqiyatallah University of Medical Sciences, Tehran, Iran. Shahrbano Rostami Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran. Bahman Jalali kondori Department of Anatomical Sciences, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran. Introduction: CLL is one of the most common leukemias, which is categorized by the accumulation of mature CD5+ B-lymphocytes in the peripheral blood, bone marrow, and secondary lymphoid organs. In this study, the status of rs6449182 polymorphism of the CD38 gene and its association with clinical and laboratory parameters of CLL patients was evaluated.  Methods: Genomic DNA extraction was performed using the salting out method. The CD38 gene polymorphism (rs6449182) was studied in 70 patients with CLL and 70 healthy individuals using the PCR-RFLP method. Results: The results of this study showed that the control group had 86% wild-type rs6449182 (CC), 12% heterozygous (CG), and 2% homozygous (GG) genotypes. In the case group, 62% had wild-type genotype (CC) 26% were heterozygous (CG), and 12% were homozygous (GG). Statistical analysis showed that the heterozygous genotype for the CD38 gene  was significantly associated with CLL. It was also understood that this polymorphism had a significant relationship with hemoglobin, age, and organomegaly of patients. Conclusions: The CD38 gene polymorphism of rs6449182 SNP G allele had the highest frequency. Moreover, based on the results, this polymorphism has a significant relationship with organomegaly, which indicates the importance of these markers in the pathogenesis and prognosis of the disease. Keywords: Polymorphism, Single Nucleotide Polymorphisms, Chronic lymphocytic leukemia (CLL), CD38  

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 14 3 2022 9 1 Significance of Cross Lineage Antigen Expression in Acute Lymphoblastic Leukemia 22 31 EN Sindhura Lakshmi Koulmane Laxminarayana Associate Professor, Department of Pathology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal - 576104, KA, India. Aradhana Harrison Assistant Professor, Department of Pathology, Melaka Manipal Medical College, Manipal, Manipal Academy of Higher Education, Manipal - 576104, KA, India. Phaneendra VR Datari Former Post graduate student, Department of Pathology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal - 576104, KA, India. Sushma V Belurkar Additional Professor, Department of Pathology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal - 576104, KA, India. Background: Aberrant expression of cross-lineage antigens gives valuable insight into the diagnosis and prognosis of acute leukemia. In countries like India, cytogenetic tests are widely accessible. Exploring the prognostic value of an accessible test is of great importance. Therefore, establishing a population-specific immunophenotype database will enable to design an antibody panel equipped to detect cross-lineage antigen expression. The aim of this study was to determine the frequencies of cross-lineage antigen expression in Acute Lymphoblastic Leukaemia (ALL), its relationship with clinical features, and changes in blood counts during the treatment course. Methods: This was a retrospective observational study conducted at a tertiary care hospital. Consecutive ALL cases over 2 years were reviewed. Relation of cross-lineage aberrant antigens with blood counts and clinical features were studied. Chi-square test and Fisher’s exact test were used. Results: A total of 149 ALL cases were included in the study. Thirty (20.1%) cases showed expression of cross-lineage antigens. CD7 was the most commonly expressed cross-lineage antigen, seen in 14 (10.5%) cases of B-ALL. CD13, seen in eight (5.3%) patients, was the most frequent aberrant myeloid antigen. Myeloid aberrancies were associated with lower WBC count and blast count while aberrancies of T-cell antigens on B-ALL showed higher WBC count and blast count. Conclusions: Cross lineage antigenic aberrancies influence blast count and WBC count. Documentation of these aberrancies in ALL helps in prognostication and monitoring of the disease.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 14 3 2022 9 1 Evans syndrome in the course of COVID-19 infection; Essentials and approaches 32 40 FA Gholamhossein Tamaddon Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran. tamaddon.g@gmail.com Pooria Fazeli Shiraz Medical Sciences mohammadreza saeidnia Shiraz Medical Sciences Arghavan Farzi Ilam Medical Sciences Navid Pooresmaeil Ilam Medical Sciences Mohammad hamed Javanmardi Shiraz Medical Sciences Redundant studies proved coronavirus infection results from a defect in a suitable immune response that may exacerbate immune-inflammatory reactions like cytokine storm and autoimmunity. Evans syndrome (ES) is a rare chronic autoimmune disease that distinguishes it from autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP). Reports have shown significant differences in immune cells and laboratory parameters in Evans syndrome/COVID-19 co-infected patients. Also, the contribution between autoimmune diseases and SARS-CoV-2 infection could result in immune response disequilibrium that considers a possible mechanism for ES development. Moreover, we will briefly explain the double-edged sword role of immunosuppressive drugs in Evans syndrome/COVID-19 co-infected patients. Generally, the pathophysiology of SARS-CoV-2 in hematologic autoimmune disorders progression, particularly ES, remains unclear, but some investigations explain the COVID-19 infection mechanism in the mentioned disorders development. The purpose of the current study is to look at the coronavirus effects on Evans syndrome aggravation, the immune cells and laboratory markers alterations in Evans syndrome/COVID-19 co-infected patients, the coronavirus effects on Evans syndrome patients during their pregnancy, and the Evans syndrome / COVID-19 co-infected patient management.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 14 3 2022 9 1 Role of Molecular Biomarkers in Colorectal Cancer 41 56 EN Muhammad Junaid Iqbal Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan Shaifa Saleem School of Biochemistry and Biotechnology, University of the Punjab, Lahore, Pakistan Uroosa Sarfraz Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan Sania Saeed Department of Biological Sciences, International Islamic University Islamabad, Islamabad, Pakistan Aghna Maryam Department of Biochemistry, Quaid-i-Azam University, Islamabad, Pakistan Colorectal cancer (CRC) is amongst the most widespread cancers and is a most common cause of cancer associated mortality universally. Since previous decades, it has been cleared that CRC develops owing to the buildup of a series of genetic and epigenetic changes in the normal colonic epithelium. Regardless of the current development in surgery and therapies, overall survival of end stage CRC patients is extremely low. Different biomarkers are valuable means found in tissue, blood, or stool samples usually, they are efficiently used for CRC monitoring, because they occur in initial stage of disease and provide better identification, diagnosis, prognostication, and prediction of cancer. An accurate biomarker-based treatment and prediction approach will help Patients to get rid of unsuccessful treatments, involving clinical trial-based methods. It will also definitely inhibit under and over dosages of treatment as well as it will decrease pointless harmful side effects. This review focusses upon epidemiology, risk factors, molecular pathways, as well as Different DNA biomarkers and RNA biomarkers related to CRC. In this review, we will highlight the existing knowledge and advances in DNA based biomarkers (RAS, BRAF, cell free DNA, DNA methylation-based biomarkers, and Microsatellite Instability) and RNA-based biomarkers (MicroRNAs, non-coding RNAs, circular RNAs and PiRNAs) for CRC. Herein, we put emphasis for gathering of the latest facts related to biomarkers for obtaining their maximum possible advantages by promoting the clinical practice. New studies show the frequent usage of biomarkers, which will help in optimizing the best possible treatment approaches ultimately.  

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 14 3 2022 9 1 Plant-derived natural compounds as promising anticancer agents in hematological malignancies 57 70 EN Forouzan Bahmani Abadan Faculty of Medical Sciences, Abadan, Iran Shima Azadpour Abadan Faculty of Medical Sciences, Abadan, Iran Atieh Pourbagheri-Sigaroodi Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran Davood Bashash Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran The latest treatments have improved outcomes for patients with hematological malignancies, but relapse, treatment resistance and particularly side effects still remain as common limitations of these treatments. Given the disadvantages of the existing conventional therapeutic methods, developing more effective drugs with less toxicity and side effects is of paramount importance. Medicinal herbs have historically proven their worth as a pool of potential therapeutic agents for leukemia and lymphoma, and today they still represent a rich source for the recognition of new drug leads. The role of the positive synergistic effects of plant-derived natural products and common chemotherapeutic drugs is also considered as one of the rational reasons for paying attention to the medicinal plants in recent chemoprevention and chemotherapeutic investigations. Noteworthy, targeted delivery of plant-derived natural products via the incorporation of nanoparticles or antibodies would be a major step to improve their bioavailability and then to increase their therapeutic effects. In this study, we reviewed plant-derived agents approved and/or under investigation for hematological malignancies.

Iranian Pediatric Hematology and Oncology Society Iranian Journal of Blood and Cancer 2008-4595 14 3 2022 9 1 Myelodysplastic Syndromes (MDS); diagnosis, classification, treatment and monitoring 71 83 EN Maryam Panahi Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran Mahmoud Dehghani Ghorbi Department of hematology and oncology, school of allied medical sciences, Shahid Beheshti University of medical sciences, Tehran, Iran Mozhgan Amirpour Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Reika Nayebi Department of Hematology and Blood Banking, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Bentol Hoda Kuhestani Dehaghi Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Due to the neoplastic nature of myelodysplastic syndromes (MDS), they have been renamed as myelodysplastic neoplasms in the World Health Organization (WHO) 2022 classification. These syndromes are heterogeneous groups of myeloid disorders characterized by dysplasia of bone marrow cells, ineffective hematopoiesis, increased apoptosis, peripheral blood cytopenia, and risk of progression to acute myeloid leukemia (AML). The recent progress in understanding the pathogenesis of these diseases is due to the emergence of next-generation sequencing (NGS) and the simultaneous interpretation of changes in cell morphologies, cytogenetics, and molecular mutations, which have provided the conditions for better classification and determination of efficient prognosis. Based on the Revised International Prognostic Scoring System (IPSS-R) system, MDS treatment approaches were divided into two groups: low-risk MDS, and high-risk MDS. In low-risk MDS, MDS is not the main cause of death, and most of the patients die as a result of cytopenia and the quality of life. Therefore, the goal of treatment approaches in low-risk MDS is to improve the quality of life in patients. However, in patients with high-risk MDS, the possibility of progression to AML is life-threatening. Therefore, clinical decisions aim to improve the course of the disease.