Iranian Journal of Pediatric Hematology & Oncology

Synthesis of Dhydropyrano[3,2-c]chromenes in the Presence of Effective Acid–Base Nano Catalyst (3-Aminopyridin/Go) and Evaluation of Their Toxicity against Cancer Cells

2026-04-27T10:25:21+00:00

Background: Dihydropyrano[3,2-c]chromenes are oxygen-containing heterocycles with reported anticancer potential, yet green and efficient synthetic methods remain limited. Conventional catalysts often involve harsh conditions or low reusability. This study aimed to develop a sustainable, high-yield synthesis of chromenes via a novel acid–based nanocatalyst (GO/3-aminopyridine), and to evaluate the cytotoxicity of selected derivatives against cancer and normal cells.

Materials and Methods: In this in vitro experimental study, we performed a one-pot, three-component reaction of 4-hydroxycoumarin, malononitrile or ethyl cyanoacetate, and aromatic aldehydes in the presence of 3-aminopyridine-functionalized graphene oxide (GO/3-APy) under mild conditions (EtOH/H₂O, 50 °C). The structure of the catalyst and products were confirmed via FT‑IR, NMR, XRD, FE-SEM, and EDS. MTT assay was used to determine IC₅₀ values for selected compounds against Ovcar3, T47D, CA46, and HFF cell lines. Doxorubicin served as a positive control. Statistical analyses were done by SPSS (Version 22.0). ANOVA test was performed to identify significant differences in IC₅₀ values across all tested compounds and doxorubicin. P-value < 0.05 was considered significant.

Results: Compound 4b exhibited potent cytotoxicity against Ovcar3 (IC₅₀ = 14.67 ± 1.15 µg/mL), T47D (26.85 ± 2.10 µg/mL), and CA46 (27.17 ± 1.55 µg/mL) cells, significantly surpassing doxorubicin against CA46 (46.07 ± 2.80 µg/mL; p < 0.05). Compound 4d showed comparable activity (IC₅₀ = 17.99 ± 1.42, 29.50 ± 1.85, and 56.62 ± 2.90 µg/mL, respectively) with high selectivity for cancer cells over normal HFF (IC₅₀ = 239.25 ± 5.50 µg/mL; selectivity index ~13). Compounds 4e, 4g, and 4h demonstrated moderate cytotoxicity (IC₅₀ = 33.50–141.52 µg/mL), while doxorubicin displayed non-selective toxicity toward normal cells (IC₅₀ = 50.45 ± 2.90 µg/mL vs. 239.25 µg/mL for 4d).

Conclusion: The results of our research showed that dihydropyrano[3,2-c]chromene derivatives showed anticancer effects that depended on the type of substitution present on the ring in their structure.

Application of Machine Learning in the Prediction of Liver Iron Concentration Using T2* MRI in the Liver of Children with Acute Lymphoblastic Leukemia

2026-04-27T08:12:37+00:00

Background: Machine Learning (ML) is a technique currently used to predict, diagnose, and treat diseases. Acute Lymphoblastic Leukemia (ALL) is the most common cancer among pediatric patients. A frequent complication in children with ALL is anemia, which leads to the need for recurrent blood transfusions. This, in turn, can result in increased Liver Iron Concentration (LIC). Currently, diagnosing LIC is performed using T2* MRI techniques; however, due to the limitations of MRI, employing ML techniques to predict LIC has become necessary.

Materials and Methods: In this retrospective cohort study, a collection of datasets was obtained from 66 children (mean age = 10.7 year) diagnosed with ALL, and three ML models were used, including Random Forest Classifier (RFC), Support Vector Classifier (SVC), and Logistic Regression (LR). Given the small sample size, a preprocessing step including feature standardization and SMOTE oversampling was taken only within the training datasets during cross-validation to prevent data leakage.

Results: Among the evaluated models, LR achieved the highest precision–recall (PR) Area Under the Curve (AUC) and receiver operating characteristic (ROC) AUC values (test PR AUC = 0.94, p-value = 0.002; CV PR AUC = 0.98 p-value < 0.001; test ROC AUC = 0.98, p-value = 0.002; CV ROC AUC = 0.98, p-value < 0.001). The permutation feature importance identified serum ferritin (SF) and transfusion volume per kilogram (TV/Kg) as the dominant predictors of LIC.

Conclusion: This study indicates that ML models are promising ones for predicting LIC. However, due to the limited sample size, future studies with larger cohorts are warranted to validate these findings.

Perspectives on Leukemia in Children under 15 Years of Age: Convergence of Clinical and Statistical Information in the Center of Iran

2026-04-27T08:12:36+00:00

Background: Leukemia is the most common childhood malignancy. Understanding its clinical manifestations and laboratory findings in different regions is essential for early detection and timely management. Despite limited exhaustive studies in central Iran, this study provides a comprehensive analysis of the clinical and laboratory data collected in Yazd Province over a ten-year period.

Materials and Methods: This retrospective descriptive study analyzed 378 children under 15 diagnosed with leukemia at Shahid Sadoughi Hospital between 2014 and 2023. Data included demographics, clinical symptoms, and blood counts. Statistical analysis was done using SPSS v20 with Chi-square and ANOVA tests, considering P < 0.05 as significant.

Results: This study included 213 males (56.6%) and 165 females (43.7%)(M: F =1.29:1), with a mean diagnostic age of 5.42 ± 3.85 years; 61.4% were ≤ 5 years old. Acute lymphoblastic leukemia (ALL) was the predominant subtype (89.7%). Fever (46%), bone pain (27.5%), and weakness/lethargy (26.2%) were the most common clinical manifestations. The subtype analysis revealed that ecchymosis and respiratory symptoms were significantly more frequent in patients with acute myeloid leukemia (AML) than in patients ALL (30.3% vs. 14.1%, P = 0.03; and 21.2% vs. 7.1%, P = 0.01, respectively), while weight loss was highest in chronic myelogenous leukemia (CML) (40%, P = 0.03). Hematologic abnormalities included anemia (85.4%), thrombocytopenia (59.2%), and hyper leukocytosis (17.2%). Median WBC was higher in CML (31 mm³), whereas median lymphocyte percentages were higher in ALL (60 %). Males also had higher RBC counts (P = 0.039).

Conclusion: The findings confirm that ALL is the predominant leukemia in this population. The disease often presents with nonspecific systemic symptoms, highlighting the critical role of complete blood count as an essential screening tool for early diagnosis. Recognizing these patterns may support earlier referral, diagnosis, and initiation of appropriate treatment.

Plasma Endocan as a Biomarker of Endothelial Dysfunction in Egyptian Children with Beta-Thalassemia Major: A Single-Center Analysis

2026-04-27T08:12:35+00:00

Background: Beta-thalassemia major (β-TM) is a transfusion-dependent disorder associated with iron overload and endothelial dysfunction. Endocan is a proteoglycan secreted by endothelial cells and has been proposed as an indicator of endothelial activation and inflammation. Children with β-TM face various problems, such as glomerular and tubular degeneration, cardiomyopathy, and endothelial damage, which require regular monitoring using a reliable and practical method. This study aimed to evaluate plasma endocan levels in Egyptian children with β-TM.

Materials and Methods: A case-control study was conducted at the Medical Research Institute, Alexandria University. The experimental group consisted of 40 children with transfusion-dependent β-TM who were aged between 12 and 16 years, and the control group involved 40 age- and gender-matched healthy children. Clinical assessments and laboratory tests, including hemoglobin, serum ferritin, and C-reactive protein, were performed. Plasma endocan levels were measured using enzyme-linked immunosorbent assay (ELISA). Data were analyzed using SPSS version 20. Appropriate parametric or non-parametric tests, based on data distribution, were applied, and a p value of < 0.05 was considered statistically significant.

Results: Children with β-TM had significantly higher plasma endocan levels than controls (median 332 vs. 44 ng/L, p < 0.001). Endocan levels did not significantly differ based on gender (p = 0.575) or splenectomy status (p = 0.986). A significant difference was observed between hepatitis C virus (HCV)-negative and HCV-positive cases (p = 0.005), with higher endocan levels in HCV-positive patients. No significant correlation was found between endocan levels and age, ferritin, or transfusion frequency (p> 0.05).

Conclusion: Children with transfusion-dependent β-TM exhibited significantly higher plasma endocan levels, as compared to the healthy controls. Endocan can serve as a potential non-invasive biomarker of endothelial dysfunction in pediatric thalassemia.

Unveiling the Clinicopathological and Molecular Spectrum of Fanconi Anaemia: Insights from a Single-Centre Experience

2026-04-27T08:12:33+00:00

Background: Fanconi anaemia (FA) is the most common cause of constitutional bone marrow failure. The pathophysiology of this disease is highly complex and still unclear. It is caused by a mutation/pathogenic variant in any of the 22 complementation groups that work together in the DNA damage repair mechanism. Approximately three-fourths of FA cases are due to defects in the FANCA gene. This study investigates the molecular and clinicopathological profiles of FA patients.

Materials and Methods: This prospective observational study screened 780 aplastic anaemia patients using chromosomal breakage analysis, and the results were positive for 60 patients, therefore labeled as FA. Baseline biodata and clinical and laboratory parameters were recorded via a questionnaire. In this study, Samples from the first 50 patients were screened for c.378803790delTCT through PCR RFLP, which revealed its presence in one patient. Ten additional samples were also screened via next-generation sequencing (NGS) for broader genetic analysis.

Results: The median age of the patients was 11.5 years (IQR 5 years), with the majority (68%) of the participants being male. Growth retardation and pancytopenia were present in 98.3% and 95% patients, respectively. A total of 20 variants were detected (2 via RFLP and 18 via NGS). Seventeen were pathogenic variants, of which 16 (80%) affected FANCA and 20% affected FANCG. Twelve variants (74%) in FANCA were deletions. c.3788-3790delTCT was detected in 3 out of 60 patients (1 through RFLP and the other 2 through NGS).

Conclusion: FA is a clinically and genetically heterogeneous disease. Patients presenting with cytopenia combined with growth retardation and somatic abnormalities should be suspected of having FA. Genetic diagnosis is necessary for confirmation. NGS can aid in the diagnosis and subtyping of patients in whom targeted/hotspot mutations are unknown.

Immune Thrombocytopenic Purpura in Patients with Inborn Errors of Immunity: A Narrative Review

2026-04-27T08:12:32+00:00

Immune thrombocytopenic purpura (ITP) is one of the autoimmune disorders characterized by isolated thrombocytopenia due to immune-mediated platelet destruction. The pathogenesis of ITP is complex, involving autoantibodies against platelet glycoproteins (GPIIb/IIIa, GPIb/IX), excessive T helper1, T helper10, Thelper17 (TH1-TH0-TH17) polarization, Treg cell deficiency, and cytotoxic destruction of platelets. Cytotoxic CD8+ T-cell-mediated platelet lysis is evidenced by perforin/granzyme release in bone marrow biopsies. The diagnosis is based on excluding the other causes of thrombocytopenia, often following common viral infections. Immune thrombocytopenia can be categorized into primary and secondary groups. Secondary immune thrombocytopenia is linked with inborn errors of immunity (IEI). These errors are heterogeneous disorders with extensive clinical presentations, ranging from recurrent infections to immune dysregulation and autoimmunity. Studies have showed that autoimmune disorders are common manifestations among patients with IEI. Approximately 25-33% of IEI patients have autoimmunity disorders, including ITP, with ~20% of chronic ITP and 40% of pediatric Evans syndrome. Sometimes, patients with ITP may progress to primary immunodeficiency in the future because they may have an undiagnosed underlying IEI. Furthermore, the evaluation of patients with ITP for possible IEI, based on a history of recurrent infections and physical examinations, is essential. The prevalence of ITP is 16.2% in common variable immunodeficiency (CVID), 72% in Wiskott Aldrich syndrome (WAS), and high in autoimmune lymphoproliferative syndrome (ALPS) and LPS-responsive beige-like anchor (LRBA) / cytotoxic T-lymphocyte associated protein 4 (CTLA-4) deficiencies. IEI-associated ITP is often severe, chronic, and refractory, thus increasing morbidity. The treatments include corticosteroids, intravenous immunoglobulin (IVIG), rituximab, and targeted therapies like sirolimus. Recent studies highlight the genetic defects (e.g., FAS, CTLA4) that drive ITP, enabling precision medicine. This review study explains the recent advances in IEI-associated ITP, focusing on clinical features, pathogenesis, prevalence, and management. It also emphasizes early IEI screening for improved outcomes.

The Role of Nutrition in Pediatric Cancer: From Mechanisms to Clinical Impact

2026-04-27T08:12:31+00:00

Pediatric cancer poses a growing public health challenge, particularly in low- and middle-income countries. While advances in diagnostics and multimodal treatments have improved survival rates, treatment-related complications-especially malnutrition-remain a critical concern. Malnutrition, encompassing both undernutrition and overnutrition, affects up to 70% of children undergoing cancer therapy and significantly impacts treatment outcomes, quality of life, and survival. The nutritional status of pediatric cancer patients is influenced by tumor-related metabolic demands, treatment side effects, and socioeconomic factors. Chemotherapy, radiotherapy, and surgery often lead to anorexia, vomiting, mucositis, and metabolic disturbances that reduce nutrient intake and alter body composition. These changes may result in impaired immunity, organ dysfunction, increased infection risk, and altered pharmacokinetics of chemotherapeutic agents. Both undernutrition and obesity are independently associated with increased treatment-related toxicity and reduced survival, particularly in solid tumors and lymphomas. Biologically, cancer alters systemic metabolism through mechanisms like increased glycolysis (Warburg effect), where tumor cells preferentially convert glucose to lactate-even in the presence of oxygen-leading to inefficient energy use and muscle catabolism. Additionally, cytokines (e.g., IL-6, TNF-α) and tumor-derived catabolic factors (e.g., PIF, LMF) accelerate lipolysis and proteolysis, depleting fat and lean mass. This metabolic derangement contributes to cancer cachexia and protein-energy malnutrition, especially in children with advanced disease. Micronutrient deficiencies-particularly in vitamins D, C, B12, zinc, and selenium-are also highly prevalent and further compromise immune and metabolic function. Though data on supplementation outcomes remain inconclusive, routine screening and correction are recommended. Moreover, emerging evidence suggests that specific nutrients-such as omega-3 fatty acids-may provide additional therapeutic benefits by modulating inflammation and preserving lean body mass. Ultimately, a proactive and personalized nutritional approach is critical to improving treatment outcomes, reducing complications, and enhancing the overall well-being of children with cancer. Future studies should further be done in this regard.

Normalization of Platelet Count after Romiplostim Treatment in a Patient with Thrombotic Thrombocytopenic Purpura: A Case Report

2026-04-27T08:12:30+00:00

Thrombotic Thrombocytopenic purpura (TTP) is the thrombotic microangiopathy (TMA) caused by the severely reduced activity of the von Willebrand factor-cleaving protease ADAMTS13. The deficiency occurs in two main forms, acquired (antibody-mediated) and inherited. Plasma exchange is the mainstay of the disease management; however, Caplacizumab, glucocorticoids, rituximab, and other immunosuppressive drugs may be added to the management protocol, particularly in refractory cases. Thrombopoietic drugs are a known therapy for idiopathic thrombocytopenia purpura (ITP). No studies have been reported so far on the effects of these drugs on the patients with TTP. In this case report, we report the treatment of a 17-year-old female with hereditary TTP and dramatically good response to romiplostim (Nplate) in a one-year follow-up without an increase in the ADAMTS13 level and thrombotic complications.