Iranian Journal of Pediatric Hematology & Oncology

Comparing the Cardiotoxic Effects of Continuous Infusion and Bolus Injection of Doxorubicin in Children with Acute Lymphoblastic Leukemia (ALL): A Randomized Clinical Trial

Seyed Mojtaba Sohrevardi — 2025-06-16

Background: Cardiotoxicity is a common complication associated with chemotherapy drugs. However, limited evidence exists regarding the cardiotoxic effects of continuous infusion versus bolus injection of doxorubicin. Since no comprehensive study has been conducted on this issue in our country—particularly in Yazd city—this study aimed to compare the cardiotoxicity of bolus injection and continuous infusion of doxorubicin in children with malignancy.

Materials and Methods: This single-blind randomized clinical trial was conducted on 61 children with acute lymphoblastic leukemia (ALL) who were treated with doxorubicin in the Oncology Department of Shahid Sadoughi Hospital. Patients were randomly assigned into two groups: one group received doxorubicin via bolus injection (n=30), and the other via continuous infusion (n=31). Cardiac function was assessed using echocardiography before treatment and again 6 months after the start of chemotherapy. Data were analyzed using the Chi-square test, and independent T test. A p-value < 0.05 considered statistically significant.

Results: The mean age of participants was 9.2 ± 3.5 years. Of the 61 patients, 31 (50.8%) were boys and 30 (49.2%) were girls. Before treatment, all patients had a normal ejection fraction (EF). After 6 months of treatment, 30 patients (96.8%) in the continuous infusion group maintained a normal EF. In contrast, only 24 patients (80%) in the bolus injection group had a normal EF after treatment. The difference between the two groups in terms of EF was statistically significant (p = 0.04).

Conclusion: The frequency of cardiotoxicity was significantly higher in the bolus injection group compared to the continuous infusion group. Therefore, continuous infusion may be the preferred method of administering doxorubicin to reduce its cardiotoxic effects in pediatric patients.

Optimizing Leukocyte Analysis for Pediatric Leukemia: A Comparison of Two Advanced Hematology Analyzers

Alifferdi Rahman Wiyono — 2025-06-16

Background: Acute lymphocytic leukemia (ALL) is a hematologic malignancy affecting the lymphoid lineage, characterized by the uncontrolled proliferation of abnormal, immature lymphocytes and their precursors. The routine use of automated hematology analyzers has become a valuable aid for clinicians in diagnosing leukemia. This study aims to examine the correlation between two automated hematology analyzers in patients with leukemia, particularly in pediatric populations.

Materials and Methods: This cross-sectional study involved 57 pediatric patients diagnosed with leukemia who were referred to the Paediatric Hematology Outpatient Clinic at Dr. Soetomo General Academic Hospital, Indonesia. After obtaining informed consent, peripheral blood samples were collected in ethylenediaminetetraacetic acid (EDTA) tubes and analyzed using the Sysmex XN-Series and Horiba Yumizen H2500 automated hematology analyzers. Parameters measured included White Blood Cell (WBC) count, Neutrophil Percentage (NEU%), Lymphocyte Percentage (LYM%), Eosinophil Percentage (EOS%), and Monocyte Percentage (MON%). Data were analyzed using SPSS version 21. Statistical tests applied included the Kolmogorov-Smirnov test, Shapiro-Wilk test, paired t-test, Wilcoxon signed-rank test, Spearman’s and Pearson’s correlation test, Passing-Bablok regression, and Bland-Altman analysis. A p-value of < 0.05 was considered statistically significant.

Results: Statistically significant differences were observed between the two analyzers in the median values of WBC count (p = 0.001) and MON% (p = 0.006), as well as in the mean value of NEU% (p = 0.024). Despite these differences, strong correlations were found across all parameters, including WBC, NEU%, LYM%, MON%, and EOS% (p < 0.01). EOS% demonstrated higher variability (S_res) = 1.48.

Conclusion: The Sysmex XN-Series and Yumizen H2500 demonstrated a good correlation in the measurement of WBC parameters in pediatric leukemia patients. However, minor variations, particularly in eosinophil percentages, may arise due to differences in measurement techniques, reagent formulations, and interlaboratory variability. Despite these variations, both analyzers are reliable for clinical use.

The Association between Recent Infections and Anemia in Children: A Secondary Analysis of the Nepal Demographic and Health Survey

Yasutaka Kuniyoshi — 2025-06-16

Background: Studies have reported transient decreases in hemoglobin levels during febrile illnesses, such as pneumonia. Nevertheless, the duration of the impact of common childhood infections on anemia assessment has not been fully elucidated. This study investigates the potential associations between recent episodes of fever, diarrhea, or acute respiratory infection (ARI) and anemia in children.

Materials and Methods: A secondary analysis of the Nepal Demographic and Health Survey datasets was conducted. Parental reports of fever, diarrhea, or ARI within the 2 weeks preceding the survey were analyzed for children aged 6–59 months. Anemia was defined as a hemoglobin level of <11.0 g/dL. The prevalence of anemia and mean hemoglobin levels were compared among children with and without recent infections, stratified by age. The association between recent infections and anemia was assessed by multiple logistic regression.

Results: Among the 6,483 children, the prevalence of anemia was 47%. Fever, diarrhea, and ARI occurred in 22%, 11%, and 11% of them, respectively. Children aged 6–11 months with recent fever had a higher prevalence of anemia. However, regarding anemia prevalence or mean hemoglobin levels, this trend was not observed in the other age groups. Multiple logistic regression analyses showed no significant associations between fever (odds ratio [OR], 1.10; 95% confidence interval [CI], 0.97–1.26, P-value = 0.13), diarrhea (OR, 0.94; 95% CI, 0.79–1.12, P-value = 0.50), or ARI (OR, 1.06; 95% CI, 0.86–1.30, P-value = 0.59) and anemia.

Conclusion: Based on the findings of this study, fever, diarrhea, or ARI were not significantly associated with anemia during the two weeks prior to the survey, with the exception of fever in infants aged 6–11 months. These findings imply that the hemoglobin levels measured two weeks post-infection likely reflect the underlying anemia status rather than the transient infection-related effects.

Overexpression of the IL-33/ST2 in Pediatric Acute Lymphoblastic Leukemia: Evaluation of the Effects of a Treatment Program

Marzieh Motaghi — 2025-06-16

Background: The study focuses on B-acute lymphoblastic leukemia (B-ALL), a common childhood blood cancer marked by an overproduction of B lymphocytes. It explores the role of cytokine expression changes, particularly Interleukin-33 (IL-33), which has both anti- and pro-tumor effects. The research assesses the expression of IL-33 and its receptor, suppression of tumorigenicity 2 (ST2), in B-ALL patients before and after chemotherapy treatment.

Materials and Methods: In this quasi-experimental investigation, peripheral blood specimens were taken from 33 newly-diagnosed/untreated ALL patients. An induction chemotherapy course was administered to ALL patients for 30 days following diagnosis. Blood samples were taken again after the completion of induction chemotherapy. 30 healthy individuals with matched age and gender were also recruited as a control group. Serum IL-33 quantities were assessed using the ELISA method. Total RNA was extracted from peripheral blood samples, and the gene expression of IL33 and ST2 was measured using real-time PCR.

Results: In B-ALL patients, the pre-treatment serum IL-33 concentrations (33.89 ± 4.38 Pg/mL) were substantially greater than the healthy group (20.66 ± 2.20 Pg/mL, P<0.02). Pre-treatment expression of IL-33 and ST2 mRNA (1.79 ± 0.18 and 1.42 ± 0.18) was also significantly higher than those in the healthy group (1.00 ± 0.10 and 1.00 ± 0.09; P<0.001 and P<0.05, respectively). After chemotherapy, serum IL-33 concentrations (22.40 ± 2.60 Pg/mL) and mRNA expression of IL-33 (0.91 ± 0.15) were significantly reduced compared to pre-treatment levels (P<0.04 and P<0.001, respectively). There were no notable differences in serum IL-33 levels or mRNA expression of IL-33 and ST2 between controls and treated patients (P<0.61, P<0.63, and P<0.48, respectively).

Conclusion: Greater expression of IL-33 and ST2 was observed in B-ALL patients, which were decreased at the end of a therapy course.

The Evaluation of the Role of Several Genes (BUB1, BUB1B, and TOP2A) and the Related Signaling Pathway in the Pathogenesis of Acute Lymphocytic Leukemia (ALL): Combination of in Silico and Experimental Analysis

Maedeh Mohammadi — 2025-06-16

Background: Acute lymphoblastic leukemia (ALL) is one of the most common cancers in children, which causes the death of many patients. Nowadays, bioinformatics approaches are widely used to identify factors involved in the pathogenesis of diseases. Given the extent of molecular pathways and genes involved in these pathways, the use of bioinformatics approaches and the experimental validation of genes is essential. In this regard, we evaluated the roles of TOP2A, BUB1, and BUB1B genes in the biological processes of ALL, as well as their expression in malignant ALL cells.

Materials and Methods: The present work is a bioinformatics and experimental study. The GSE102301 database was used in this study. After determining Differentially Expressed Genes (DEGs), cell lines were used to evaluate gene expression. The cell line used in this study was CCRF-CEM. The expression of TOP2A, BUB1, and BUB1B genes for validation was evaluated using real-time polymerase chain reaction (RT-PCR).

Results: In this study, 72 DEGs were identified in ALL patients compared to the control subjects. Out of 4234 DEGs, 35 genes were up-regulated and 37 genes were down-regulated. The expression of BUB1, BUB1B, and TOP2A was increased in CCRF-CEM cells compared to peripheral blood mononuclear cells (PBMCs). The difference in the expression of these genes between the two cell types was statistically significant (p < 0.05).

Conclusion: The findings suggest that BUB1, BUB1B, and TOP2A are significantly overexpressed in ALL cells and may play a role in the disease's pathogenesis. These genes warrant further investigation as potential biomarkers and prognostic indicators in ALL, especially in clinical patient cohorts.

Beyond the Blockage: A Deep Dive into the Pathogenesis of Vaso-Occlusive Crisis in Sickle Cell Disease

Maedeh Mohammadi — 2025-06-16

Vaso-occlusive crisis (VOC) is the hallmark and most debilitating complication of sickle cell disease (SCD), yet its pathophysiology is multifactorial and not completely understood. This review examines the molecular and cellular events that drive VOC, highlighting the synergistic interaction between hypoxia, inflammation, and coagulation. Recurrent deoxygenation triggers hemoglobin S polymerization, causing red blood cell (RBC) sickling, loss of deformability, and microvascular obstruction. These events lead to endothelial activation, leukocyte adhesion, and platelet-leukocyte aggregation, fostering a hyperinflammatory, prothrombotic milieu. The increase in oxidative stress and release of cytokines result in neutrophil extracellular trap (NET) formation, exacerbating vascular injury and sustaining thromboinflammation. Together, these processes form a self-perpetuating loop, where hypoxia-induced inflammation and immunothrombosis reinforce VOC onset and severity. By elucidating these interlinked pathways, the review highlights novel therapeutic targets, particularly those modulating endothelial dysfunction, platelet-neutrophil crosstalk, and NET-driven coagulopathy. These mechanistic insights open new avenues for targeted interventions aimed at disrupting the VOC cycle and improving clinical outcomes in SCD. VOC in SCD represents a complex, self-amplifying pathological cascade driven by the interconnected processes of hypoxia, inflammation, and coagulation. Hypoxia, initiated by microvascular occlusion and compounded by impaired hemoglobin oxygen delivery, triggers a systemic inflammatory response, mobilizing innate and adaptive immune cells that further damage the endothelium and perpetuate vascular obstruction. Concurrently, hypoxia-induced activation of ECs and platelets facilitates a hypercoagulable state, characterized by TF expression, NETosis, and impaired anticoagulant mechanisms. These thromboinflammatory events not only exacerbate local ischemia but also extend systemically, contributing to multi-organ dysfunction and long-term morbidity in SCD patients. This review aims to provide an in-depth analysis of the molecular and cellular mechanisms that underlie VOC in SCD, with particular emphasis on the roles of hypoxia, inflammation, and coagulation.

Hematopoietic Stem Cell Transplantation and Immune System Suppression in Severe Aplastic Anemia

Hassan Mahmoodi-Nesheli — 2025-06-16

Aplastic anemia (AA) is characterized by pancytopenia and hypocellular bone marrow and can be either acquired or constitutional. Acquired AA results from autoimmune-mediated destruction of hematopoietic stem cells, often triggered by toxic agents inducing neo or cryptic antigens that activate immune responses. Although rare, acquired AA remains a serious condition typically managed with immunosuppressive therapy and supportive care. Constitutional forms, such as Fanconi anemia (FA) and Dyskeratosis Congenita (DC), are also uncommon and associated with genetic defects in DNA repair or telomere maintenance. Accurate differentiation between acquired and constitutional AA is critical for effective management.

In our center, 15 patients were diagnosed with AA between 2016 and 2021 (acquired = 5, constitutional = 10). Patients with acquired AA received immunosuppressive therapy. Those with constitutional AA and HLA-matched donors underwent bone marrow transplantation following a conditioning regimen of busulfan, cyclophosphamide, and rabbit ATG. Cyclosporine was initiated two days prior to transplantation and continued for 6–12 months or longer. Despite the high mortality risk associated with untreated AA, all patients achieved favorable outcomes with no mortality, underscoring the critical role of early diagnosis and individualized treatment in improving survival in AA.

Gingival Enlargement and Facial Petechiae: Early Indicators of Pediatric Leukemia

Hussein Fathy Abo-elkheir — 2025-06-16

In 2020, there were 311,594 deaths due to leukemia. It is reported that leukemia accounts for only 4% of new cancer cases in males and 3% in females. Nevertheless, leukemia is the most common malignancy in children and adolescents. Childhood leukemia is typically diagnosed by pediatricians or family doctors. This report presents a case of leukemia in a 14-year-old male, initially suspected by a dentist at a dental hospital, with the diagnosis confirmed by a complete blood count laboratory test. Gingival enlargement and petechiae throughout the body—especially on the face and arms—were key signs leading to suspicion and diagnosis, which had previously been overlooked by the family doctor and an otorhinolaryngology (ENT) consultant.