Iranian Journal of Pediatric Hematology & Oncology

Clinicopathological Analysis of Pediatric Brain Tumors: A Single-Center Study

Mahlagha Zahedi — 2025-09-14

Background: Pediatric brain tumors, comprising 20-25% of childhood cancers, are the second most common pediatric malignancy with a global incidence of 2-5 per 100,000 children, varying by region and healthcare access. In high-income countries, advanced MRI and molecular diagnostics based on the 2021 WHO classification have improved the survival rates to 70-80%. In low- and middle-income countries like Iran, limited neuroimaging, neurosurgery, and molecular profiling cause diagnostic delays of 4-6 months, disease advancement, and survival rates below 60%.

Materials and Methods: A cross-sectional descriptive study was conducted at Shahid Rahnamoun Hospital, Yazd analyzing 32 pediatric patients (aged ≤ 15 years) diagnosed with brain tumors from 2013 to 2023. The data on demographics, presenting symptoms, tumor types and locations, were extracted from pathology department records. The tumors were classified histologically according to the 2021 World Health Organization (WHO) central nervous system tumor classification, without routine molecular subtyping due to resource constraints. Statistical analysis was performed using Fisher’s exact tests in SPSS version 22, with the level of significance set at p < 0.05.

Results: The patients had a mean age of 7.1 ± 3.5 years, and the male-to-female ratio was 1.3:1. Astrocytoma was the most common tumor (40.6%), followed by medulloblastoma and glioblastoma (12.5%, each). The frontal lobe (22.2%) and cerebellum (19.4%) were the most frequent tumor sites. Headache (56.3%) and seizures (37.5%) were the prevalent symptoms. The significant associations included cerebellar tumors with balance disorders (p = 0.006), fourth ventricle tumors with speech disorders (p = 0.018), and thalamic tumors with decreased consciousness (p = 0.002).

Conclusion: This study highlights the distinct clinicopathological patterns of pediatric brain tumors in Yazd, with elevated meningioma rates suggesting potential diagnostic biases or environmental influences. Improved imaging, molecular profiling, and multicenter investigation of regional risk factors are essential to enhance the outcomes in Iran.

Investigating the Immunological Significance of TGFB1 and MDA in ALL TME

Yibei Song — 2025-09-14

Background: The tumor microenvironment (TME) in acute lymphoblastic leukemia (ALL) significantly shapes disease progression and therapeutic responses. This study investigates the regulatory role of bone marrow mesenchymal stem cell (BMSC)-released transforming growth factor beta-induced factor homeobox 1 (TGIF1) on myeloid nuclear differentiation antigen (MNDA) expression, immune infiltration, and patient prognosis in ALL.

Materials and Methods: A comprehensive bioinformatics approach analyzed gene expression, protein interactions, and immunological correlations. Differential expression, enrichment analyses, and protein-protein interaction (PPI) networks identified key regulatory genes. The relationship between TGIF1 and MNDA and their immunological impact were assessed through correlation and survival analyses.

Results: Differential analysis identified 424 differentially expressed genes (DGEs). The PPI network and Cox regression highlighted MNDA as a significant gene associated with patient outcomes. High MNDA expression correlated with better survival (P=0.013), and ROC analysis demonstrated its strong prognostic potential (AUC=0.934). GSEA indicated MNDA involvement in immune-related signaling pathways. Immune infiltration analyses linked MNDA expression to seven immune cell types. Additionally, transcription factor TGIF1 positively correlated with MNDA expression, significantly upregulated in healthy BMSCs but downregulated in ALL samples.

Conclusion: BMSC-derived TGIF1 positively regulates MNDA expression, influencing immune infiltration and ALL progression. Targeting the interplay between TGIF1 and MNDA introduces a new molecular strategy for managing ALL.

Developing a Model for the National Pediatric Cancer Registry

Farkhondeh Asadi — 2025-09-14

Background: A pediatric cancer registry is a crucial tool for collecting and managing health care data. The development of a national registry model for pediatric cancer is vital for organizing and overseeing data effectively. This study aimed to develop a model of the national pediatric cancer registry in Iran.

Materials and Methods: This study is an applied type. In the first phase, a systematic search was conducted across the PubMed, Web of Science, and Scopus databases. Additional grey literature was also explored through targeted Google searches. Some keywords related to pediatric cancer and registry were used to extract components for a national pediatric cancer registry model. Colombia, Denmark, China, and Indonesia were selected for a comparative study due to their comprehensive registry information, emphasis on registry processes, and geographical diversity. In the second phase, the proposed national pediatric cancer registry model was presented. In the third phase, the model was validated through a two-step Delphi technique using a questionnaire.

Results: This study identified key components of a national pediatric cancer registry. Four main components, including general information, organizational structure, content, and registry process, were identified as the main components of the national pediatric cancer registry model in Iran. Using a two-stage Delphi technique, 37 model components were systematically reviewed, and the final approval was achieved with the consensus of all the experts.

Conclusion: The proposed model establishes a robust informational infrastructure to enhance the collection, management, and oversight of pediatric cancer data nationally. It is expected to improve survival monitoring and the quality of care, although further research is essential to evaluate its real-world effectiveness in Iran.

Challenges and Developments in Prenatal Diagnosis of Beta-Thalassemia: A Study on Diagnostic Accuracy

Bijan Keikhaei — 2025-09-14

Background: Beta-thalassemia major is prevalent in areas like Khuzestan, Iran, and causes severe anemia requiring lifelong treatment. Despite successful prevention programs, diagnostic errors in Prenatal Diagnosis (PND) persist, leading to affected births. This study evaluates the accuracy of PND, identifies the causes of errors, and suggests improvements to diagnostic protocols.

Materials and Methods: A retrospective descriptive cross-sectional study (2012–2018) with 202 beta-thalassemia carrier couples from Shafa Hospital, Ahvaz, Iran. Fetal DNA analysis was conducted via Chorionic Villus Sampling (CVS) and amniotic fluid sampling using Amplification Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR), Gap Polymerase Chain Reaction (Gap-PCR), and sequencing. Statistical analysis results revealed factors influencing diagnostic errors.

Results: Affected infants were diagnosed with beta-thalassemia major at an average age of five months. The results showed six diagnostic errors (2.14%), primarily associated with point mutations. Errors occurred more frequently in amniotic fluid sampling (4.05%) than in CVS sampling (1.45%). CD 36/37, IVS-II-1, and Fr8–9 were the most common detected mutations.

Conclusion: Improving the accuracy of PND for beta-thalassemia is crucial, particularly in regions with high prevalence, such as Khuzestan, Iran. Although the overall diagnostic error rate was low (2.14%), the consequences of such errors are significant. The diagnostic error can lead to the birth of affected children and an added burden on families and healthcare systems. Most errors were linked to point mutations and were more frequent in amniotic fluid sampling than in CVS. To minimize such diagnostic mistakes, advancements in molecular diagnostic techniques—especially for detecting rare mutations—are necessary.

The Effect of Iron Therapy on Electrocardiography Parameters in Children with Iron Deficiency Anemia

Noor Mohammad Noori — 2025-09-14

Background: Iron is essential for hemoglobin (Hb) production and the body's ability to transport oxygen. This study aimed to evaluate the impact of iron deficiency anemia (IDA) on electrocardiographic (ECG) parameters in children.

Materials and Methods: This pre–post interventional study was carried out at Ali Asghar Hospital in Zahedan and included children aged 5 to 18 years diagnosed with IDA. For each participant, hematologic markers Hb, ferritin, serum iron, and total iron-binding capacity (TIBC) were assessed. In addition, ECG indices, including P wave duration (PWd), QT interval dispersion (QTd), corrected QT interval (QTc), Tp-e interval, and Tp-e dispersion, were recorded both at baseline and after three months of iron therapy.

Results: A total of 45 children (mean age: 11.47 ± 4.00 years) participated in the study. After three months of treatment with 4–6 mg/kg/day of elemental iron, significant improvements were observed in several hematological and ECG parameters, including ferritin, serum iron, TIBC, P wave duration, P wave dispersion, QTc, QTc dispersion, Tp-e interval, Tp-e dispersion, and the Tp-e/QTc ratio (p < 0.001). In children with Hb levels between 10 and 11 g/dL, all ECG parameters improved significantly (p < 0.001), while those with Hb levels between 8 and 9 g/dL showed significant improvement in all parameters except the Tp-e/QTc ratio (p = 0.002). Among children with ferritin levels >10 ng/mL, all ECG parameters improved (p < 0.001), whereas in those with ferritin ≤10 ng/mL, all but QTc showed significant changes (p =0.002). Serum iron levels between 15 and 20 µg/dL were associated with improvements in all evaluated parameters (p = 0.002), while those with levels between 21 and 28 µg/dL demonstrated significant changes only in TIBC and P wave duration (p = 0.002).

Conclusion: The study concluded that the Iron supplementation positively impacts hematological and ECG parameters, supporting heart health in children.

Utilizing Neutrophil Extended Parameters for the Screening of Early-Onset Neonatal Sepsis

Nik Noor Fadhilah Nik Mansor — 2025-09-14

Background: Early-onset neonatal sepsis (EOS), occurring within the first 72 hours of life, is a significant cause of morbidity and mortality in newborns. Prompt diagnosis remains a challenge due to the nonspecific nature of clinical signs and the delayed results from standard diagnostic methods such as blood culture. Traditional hematological markers, including total neutrophil count and the immature-to-total neutrophil (I: T) ratio, have shown limited sensitivity and specificity in the early detection of EOS. This study investigates the diagnostic utility of both conventional and novel neutrophil indices, such as absolute neutrophil count (ANC), immature granulocyte (IG) count, I: T ratio, and the advanced scatter-based parameters Neut-Y (neutrophil reactivity index) and Neut-X (neutrophil granularity index), using automated hematology analyzers to improve the early identification of EOS.

Materials and Methods: This prospective study analyzed clinical data from 135 presumed sepsis neonates identified as having maternal and fetal risk factors for early-onset neonatal sepsis. Blood investigations, including full blood counts, differential counts using the Sysmex XE-series (Sysmex Corporation, Kobe, Japan), and blood cultures, were performed. Biochemical markers and neutrophil parameters were analyzed to distinguish sepsis cases from non-sepsis cases.

Results: ANC and neut-Y (neut-RI) were found to be significant biomarkers for early-onset neonatal sepsis (p < 0.05). These two parameters can be used to differentiate between sepsis and non-sepsis, with a cut-off value of ANC and neut-Y (neut-RI) as 8.46 x 10³/ul and 33.85ch, respectively.

Conclusion: ANC and neut-Y are promising tools for screening early-onset neonatal sepsis. The clinical history of risk factors supplemented with these two parameters will help to identify neonates who are at risk of sepsis and assist in further and prompt management.

Serum Iron, Zinc and Ferritin in 6 to 12-Year-Old Children with Giardia lamblia Positive and Healthy Children in Urmia City

Ali Fattahi Bafghi — 2025-09-14

Background: Giardia lamblia is the most common cause of acute non-viral diarrhea worldwide and resides in the small intestine, leading to Steatorrhea, growth and cognitive retardation, and trace element deficiencies. This study aimed to compare serum iron, zinc, and ferritin levels between 6- to 12-year-old children infected with Giardia lamblia and healthy controls in Urmia, West Azerbaijan Province, Iran.

Materials and Methods: A case-control study was conducted with 35 children infected with Giardia (cases) and 35 healthy children (controls), aged 6–12 years, selected from 325 children referred to health centers in Urmia. Blood samples (5 mL) were collected from all participants and stored for later analysis. Serum concentrations of iron and zinc were measured using atomic absorption spectrophotometry, and ferritin levels were assessed by ELISA. Data were analyzed using mean, standard deviation (SD), and variance, and statistical comparisons were performed. The relationship between serum ferritin and zinc concentrations was evaluated using Student’s t-test.

Results: Serum iron levels were significantly lower in Giardia-infected children compared to healthy controls (P = 0.03). Serum zinc levels were also significantly lower in the infected group (P = 0.001). The mean ferritin level was 59 ± 34 ng/dL in children with Giardia compared to 110 ± 43 ng/dL in the control group, and this difference was statistically significant (P = 0.001).

Conclusion: These findings indicate that Giardia lamblia infection in children is significantly associated with lower serum levels of iron, zinc, and ferritin. Early diagnosis and treatment of giardiasis could help prevent nutrient deficiencies and related complications such as growth retardation and impaired immune function. Timely intervention may reduce long-term developmental and health risks in affected children.

Five-Year Survival, Mortality, and Relapse Rate of Childhood Leukemia in Iran: A Systematic Review and Meta-Analysis

Mahsa Adibifar — 2025-09-14

Background: Childhood leukemia (CL) is a cancer that occurs mostly in children and adolescents. A comprehensive image of the survival, mortality, and relapse rate in leukemia in Iran is less visible. Therefore, the current study aimed to estimate the five-year survival, mortality, and relapse rates of CL in Iran.

Materials and Methods: The current systematic review and meta-analysis examined all observational studies in English and Persian that were published from January 2000 to July 2024 in different international databases, including Google Scholar, Web of Science, PubMed, Scopus, and local databases such as SID, IranDoc, Magiran, and IranMedex. The statistical heterogeneity was assessed using the I2 index, Tau2, and the Q test. Due to high heterogeneity (I2 > 50%), a random-effect model was used for pooled estimation. The Beggs and Eggers test served to assess the publication bias. Sensitivity analysis was performed to determine the influence of individual studies on the pooled estimate.

Results: A total of 22 relevant manuscripts that reported the mortality, survival, and relapse rate of Childhood leukemia were reviewed and analyzed in this study. The 5-year survival rate of childhood leukemia in Iran was 63% (95% CI: 57%- 70%, I2: 94.57, P < 0.001). The survival rate in ALL and AML cases were 66% (95% CI: 58%- 74%, I2: 95.80, P < 0.001) and 58% (95% CI: 48%- 68%, I2: 83.13, P < 0.001), respectively. The 5-year mortality and relapse rates in childhood leukemia were also 26% (95% CI: 21%-31%, I2: 89.76, P < 0.001) and 24% (95% CI: 18%-30%, I2: 90.09, P < 0.001), respectively.

Conclusion: The 5-year survival rate in Iranian children with leukemia is not very high, and the death and recurrence rates caused by the disease are remarkable. Therefore, developing health and treatment infrastructure to reduce morbidity and improve patient survival is inevitable.

The Role of Non-Governmental Organizations (NGOs) in Pediatric Cancer Care: Psychosocial, and Economic Perspectives

Masih Ganji Ashtijeh — 2025-09-14

Childhood cancer represents a major global health challenge and remains one of the leading causes of death among children, particularly in low- and middle-income countries where more than 80% of cases occur. The rising incidence is attributed to factors such as population growth, aging, tobacco use, poor dietary habits, obesity, sedentary lifestyles, and exposure to infection-related carcinogens. In addition to the clinical burden, families of children with cancer face significant psychosocial and financial challenges, which can compromise both caregiver well-being and treatment outcomes. These challenges highlight the need for comprehensive strategies that go beyond medical care to include psychosocial and socioeconomic support.

Non-governmental organizations (NGOs) have emerged as important actors in addressing these gaps. Their independence, community orientation, and voluntary nature enable them to provide services that governments and healthcare systems often overlook. This review highlights the multifaceted contributions of NGOs in pediatric cancer care, including psychosocial interventions, financial assistance, advocacy, and policy engagement. Evidence shows that interventions such as cognitive behavioral therapy, problem-solving skills training, and family therapy effectively reduce caregiver stress, anxiety, and depression, while enhancing coping abilities and indirectly improving children’s treatment outcomes. At the same time, NGOs play a crucial role in reducing the economic burden of cancer care by mobilizing resources, covering out-of-pocket expenses, and facilitating access to services in resource-limited settings.

Examples from Iran, India, and global studies demonstrate that NGO-led initiatives can enhance psychosocial well-being, and increase access to healthcare. Strengthening these efforts represents a promising approach to reducing caregiver burden and improving the quality of life of children with cancer. Future research should explore sustainable models of NGO involvement, and policymakers are encouraged to integrate NGO capacities into national pediatric cancer control strategies.

Pediatric Adrenocortical Carcinoma: Diagnostic Challenges and Therapeutic Approach — A Case Report

Assia Haif — 2025-09-14

Adrenocortical carcinoma (ACC) is a rare tumor. It constitutes 0.2% of malignant tumors in children and it is considered ten times rarer than in adults. Patients with predisposing syndromes like Li-Fraumeni or Beckwith-Wiedemann may develop these tumors.

Clinical symptoms are dominated by endocrine signs, which are present in 90% of cases. The primary cause is virtualization syndrome, which may occur alone or in conjunction with secondary symptoms caused by hypersecretion of adrenal hormones.

Imaging is indispensable in assessing the malignant nature of the adrenal tumor and its extent. Currently, surgical excision of the tumor is the cornerstone of treatment because its quality often depends on the prognosis of the disease. Adrenocortical carcinoma has a poor prognosis despite treatment, with high chances of recurrence and mortality.