Iranian Journal of Pediatric Hematology & Oncology

Comparison of the Effect of Chlorhexidine Mouthwash and Combined Mouthwash (4 drugs) in Preventing and Managing Oral Mucositis in Neutropenic Patients Admitted to the Pediatric Oncology Department: A Randomized Clinical Trial

Roohollah Edalatkhah — 2025-03-16

Background: Given the lack of comprehensive studies comparing the effects of chlorhexidine and combined mouthwashes in preventing oral mucositis in our country, particularly in Yazd province, this study aims to evaluate the effectiveness of combined mouthwash versus chlorhexidine mouthwash in preventing oral mucositis in neutropenic patients.

Materials and Methods: This study was a double-blind randomized controlled trial conducted on children undergoing chemotherapy at Shahid Sadoughi Hospital. Patients were randomly assigned to two groups of 30: one group received combined mouthwash containing diphenhydramine, nystatin, aluminum-magnesium hydroxide, and lidocaine (group 1), while the other group received a 0.2% chlorhexidine mouthwash (group 2). The interventions were administered orally at least twice daily for one month.

Results: The frequency of pain intensity and mucositis in the two groups was similar on the 14th and 28th days (100% of patients were free from pain and mucositis). Additionally, no significant difference was observed between the two groups in terms of pain intensity and frequency of mucositis on the 7th and 21th days (p > 0.05). On the 7th day, the frequency of grade 1 mucositis was 3.4% in group 1 and 3.3% in group 2, with no statistically significant difference in the severity of mucositis between the two groups (p = 0.981). On the 21th day, the frequency of grade 3 mucositis was 3.4% in group 1 and 0% in group 2; however, there was no statistically significant difference in the severity of mucositis between the two groups on the 21th day (p = 0.305).

Conclusion: Although there was no statistical difference in reducing pain severity, mucositis frequency, or mucositis grade between the two groups, chlorhexidine was found to be more effective and satisfactory in practice. Therefore, considering its lower cost, chlorhexidine is recommended as a cost-effective option for the treatment of oral mucositis.

Psychometric Properties of the Persian Version of the Pediatric Quality of Life Inventory 3.0 (PedsQL™) Cancer Module

Afsoon Hassani Mehraban — 2025-03-16

Background: Pediatric cancer significantly impacts children's physical, emotional, and social well-being, making quality of life (QoL) assessment essential. The Pediatric Quality of Life Inventory 3.0 (PedsQL™ 3.0) includes both child self-report and parent proxy versions, which are widely used to evaluate QoL in children with chronic conditions, including cancer. However, validating its psychometric properties across different cultural contexts is necessary.

Materials and Methods: A methodological research design was employed for a sample of 200 participants including 100 inpatient children with cancer (mean age ± SD: 9.30 ± 1.85 years) and their mothers (mean age ± SD: 33.61 ± 6.03 years). The content, face, and structural validities of the study were assessed using exploratory factor analyses. The test reliability was also measured through internal consistency calculated with Cronbach's alpha. Moreover, the intra-class correlation coefficient (ICC) was used to evaluate the test-retest reliability.

Results: The results of the study demonstrated acceptable content and face validity for both the child and mother versions of the instrument. The structural validity analysis revealed a five-factor structure for the child version and a six-factor structure for the mother version. The reliability of the instrument was confirmed with satisfactory Cronbach's alpha values (α = 0.85) for both versions, indicating strong internal consistency. Additionally, the inter-rater reliability was assessed with ICC. The assessments yielded the values of 0.87 for the child version and 0.88 for the mother version, suggesting excellent agreement.

Conclusion: The Persian version of the PedsQL™ 3.0 is a valid and reliable tool for assessing the quality of life in children with cancer and their mothers.

Prevalence, Disease Manifestations and Outcomes of Paediatric Sickle Cell Anaemia in Calabar, Nigeria: A Single Center 6-Year Review

Anthony Nlemadim — 2025-03-16

Background: The burden of sickle cell anaemia (SCA) is worsening globally. Recognition of paediatric SCA burden is vital to comprehending the overall SCA burden. Aim was to determine the prevalence, disease manifestations and outcomes of paediatric SCA.

Materials and Methods: It was a retrospective study of all children with SCA, 0.5 year (6months) - 17 years old, managed from 2018 through 2023. Data obtained were sex, age at first visit per year, diagnoses and date per visit, location (clinics or emergency-room) of visit, intervals between visits, and death. Disease manifestations per subject were summarized into diagnosis while default was defined as >3 months visit interval.

Results: Of the 532 subjects, 55.6% were males with overall median (interquartile [IQR]) age on first visit of 9 (5 - 13) years. On average, paediatric SCA constituted 4% of first visits per year. There were 252 sick visits per year, 544 diagnoses per year and 146 hospitalisations per year. Commonest diagnosis in emergency-room and clinics were bone pain crises (46.2%) and steady-state (48.5%), respectively. The 11 - 17-year-olds were more likely to have bone pain crises than 0.5 - 4-year-olds (Odds Ratio [OR] 0.381; 95%CI: 0.487-0.787) and 5 - 9-year-olds (OR 0.298; 95%CI: 0.573-0.861). They were also more likely to have avascular necrosis than the 0.5 - 4-year-olds (OR 0.789; 95%CI: 0.047-0.938) and 5 - 9-year-olds (OR 0.777; 95%CI: 0.064-0.781). Overall median (IQR) default time was 6 (5 - 7) months with more defaults (85.1%) than compliants (14.9%) (p<0.001) while 0.56% died.

Conclusion: The overall prevalence of Paediatric SCA in the region is 4% with approximately one hospitalisation per sick visit and more than one diagnoses per visit. There is a high default rate but a low mortality rate (0.56%). Sustained improvement in the management of SCA, from childhood through adulthood, may help alleviate the increasing burden of the condition.

Molecular Characterization of Coagulation Factor V and Combined Factors V and VIII Deficiencies in the Northeast of Iran

Faeze Bamian — 2025-03-16

Background: The deficiencies of Factor V (F5) and combined Factors V and VIII (F5F8D) are known as two rare bleeding disorders. This study aimed to evaluate the studied patients' demographic, laboratory data, and nucleotide changes.

Materials and Methods: This is a cross-sectional study of twelve and five patients affected by F5 deficiency and F5F8D, respectively. The study was conducted at Mashhad University of Medical Sciences, from 2015 to 2016. The mean age of the patients with F5 deficiency was 33.91 ± 18.94 years, and that of the patients with F5F8D was 29.40 ± 9.20 years. The coagulation factor assay was performed, and all the exons and intron-exon junctions of LMAN1, MCFD2, and Factor V genes were amplified and subsequently sequenced.

Results: The prevalence of F5 deficiency and F5F8D in the Khorasan Razavi population was 7 and 5 per 1,000,000, respectively, which is higher than the estimated worldwide prevalence of 1 per 1,000,000 to 2 per 2,000,000. There were c.2051 G > A, c.6305 G > A, and c.1340 C > G found in the patients with F5 deficiency. Also, those with F5F8D were found to have c.822 G > A and c.149 +1 G > A.

Conclusion: The most common nucleotide change in the patients with F5 deficiency was the missense mutation c.6305 G>A in the C2 domain of exon 23 of the factor V gene. In contrast, patients with F5F8D exhibited splice site mutations, specifically c.822 G>A and c.149 +1 G>A, with homozygous inheritance. These findings suggest a distinct genetic pattern for each disorder within the Khorasan Razavi population. To better understand the correlation between factor levels and these nucleotide changes, and to explore the genetic background of other patients, further research involving a larger cohort and more advanced genetic tools, such as whole exome sequencing, is recommended.

Enhancing Platelet Preservation through Freeze-Drying and Sterilization: An Approach for the Improvement of Hemostatic Treatment and Platelet Concentrate Supply

Vahideh Takhviji — 2025-03-16

Background: The limited shelf life of platelets has led to an increasing demand for longer-lasting products. This study aimed to develop a lyophilization protocol to preserve platelets by using trehalose, a desiccation-resistant sugar, and comparing its effectiveness to sucrose, a standard sugar for protein lyophilization.

Materials and Methods: In this interventional study, the platelets were loaded with trehalose (30, 60, or 100 mM) and 2% sucrose and then freeze-dried. Evaluations were performed of platelet count, aggregation responses to the agonists thrombin (1 U/ml), collagen (2 µg/ml), adenosine diphosphate (ADP) (20 µM), and the expression of the activation surface marker CD62P. Gamma radiation (30 and 40 kGy) was evaluated for pathogen inactivation in lyophilized products through measuring the reduction factors for viral titers (Herpes Simplex Virus-1 (HSV-1) and Poliovirus) and bacterial titers (S. epidermidis and E. coli). The analyses were conducted using SPSS v23.0.1 and GraphPad Prism v10.

Results: The platelet count in the 60 mM trehalose group showed no significant change after lyophilization (mean difference: 78.33; P = 0.31). The flow-cytometry analysis revealed a significant increase of CD62P in the control and sucrose-treated groups (P < 0.01 for all the groups), while trehalose significantly preserved the platelet function. This was demonstrated by lower CD62P (7.88%, P = 0.000) and higher thrombin-induced aggregation (53.46%, P = 0.01) and ADP-induced aggregation (29.8%, P = 0.001) compared to the other groups. Gamma radiation achieved a 5.2-log reduction at 30 kGy and a 6.2-log reduction at 40 kGy for Poliovirus, along with a consistent 7-log reduction for HSV-1 at both. Additionally, titers of S. epidermidis and E. coli were reduced by more than 7 logs, rendering them undetectable.

Conclusion: Lyophilized platelets stabilized with trehalose and sterilized with gamma radiation represent a promising approach for dealing with the current limitations in platelet storage and availability

The Role of Autophagy-Associated Genes in the Pathogenesis of Patients with Acute Lymphoblastic Leukemia

Mahdieh Mehrpouri — 2025-03-16

Background: Expanding the knowledge of the underlying molecular mechanisms in acute lymphoblastic leukemia (ALL) is of great importance to improving treatment outcomes. Autophagy, a critical and evolutionarily conserved pathway, plays an important role in maintaining cellular homeostasis under stressful conditions. This pathway consists of several sequential steps. The present study aimed to evaluate the expression levels of autophagy-related protein 3 (ATG3), autophagy-related protein 5 (ATG5), autophagy-related protein 7 (ATG7), autophagy-related protein 14 (ATG14), and urothelial cancer-associated 1 (UCA1) genes in B-ALL patients in order to better comprehend the autophagy pathway in B-ALL.

Materials and Methods: This research is a case-control study. The bone marrow of 50 newly diagnosed patients with B-ALL (mean age = 12.3 years) and 15 healthy controls (mean age = 13.4 years) was evaluated by real-time PCR to analyze the expression of the aforementioned genes. Additionally, morphological, immunophenotypic, and molecular analyses were conducted to examine the phenotypes, genotypes, and percentage of lymphoblasts, respectively.

Results: The findings revealed that B-ALL patients exhibited significantly higher expression of ATG3, ATG5, ATG7, and ATG14 genes compared to the healthy volunteers (P < 0.001). However, there was no significant difference in UCA1 levels between the two groups (P > 0.05). Interestingly, ATG3, ATG5, ATG7, ATG14, and UCA1 had similar mRNA expression levels in the patients with different types of chromosome abnormalities and immunophenotypes.

Conclusion: Based on these results, the substantial increase in the expression of ATG3, ATG5, ATG7, and ATG14 genes suggests that the autophagy pathway is activated in B-ALL patients. This activation may contribute to tumor growth. Furthermore, the detection of autophagy gene expression could serve as a novel marker to monitor the response of B-ALL patients to treatment.

Pediatric Buccal Epigenetic (PedBE) and Neonatal Epigenetic Estimator of Age (NEOage) Clocks: A Focus on Pediatric Oncology

Amirhossein Omidi — 2025-03-16

The Pediatric Buccal Epigenetic (PedBE) and Neonatal Epigenetic Estimator of Age (NEOage) clocks provide a novel method for assessing the biological age of young individuals, enhancing our comprehension of their health and development. By analyzing DNA methylation patterns, these clocks identify risk factors for various health conditions and guide personalized interventions to promote optimal growth in children and infants. With ongoing research and validation, PedBE and NEOage could revolutionize pediatric and neonatal healthcare by facilitating early detection of age-related changes and targeted interventions to improve long-term outcomes. In pediatric oncology, PedBE is particularly promising for evaluating biological age in children with cancer, as it accurately estimates DNA methylation age in buccal cells, revealing the effects of cancer and its treatments on biological aging. Additionally, PedBE can detect DNA methylation changes associated with environmental exposures and childhood adversities, making it a valuable tool for studying the impact of cancer on the epigenetic age of pediatric patients. The NEOage clock, designed to predict gestational age in newborns, complements the PedBE clock, offering a comprehensive assessment of biological age from infancy to adolescence, which is vital for understanding pediatric oncology’s influence on aging. This paper examines the complexities of both clocks, highlighting their potential for accurately determining the age of children and infants through DNA methylation analysis.

Acute Lymphoblastic Leukemia Masquerading as Idiopathic Hypereosinophilic Syndrome in an Adolescent Male: A Case Report and Review of Diagnostic Strategies

Ruchee Khanna — 2025-03-16

Acute lymphoblastic leukemia (ALL) accompanying with hypereosinophilia is an extremely rare blood cancer, with an incidence rate of less than 1%. In most cases, patients with ALL and hypereosinophilia rarely show blasts in the peripheral blood, which can potentially lead to misdiagnosis. This study presents a case of an 18-year-old male who was initially diagnosed with Idiopathic Hypereosinophilic Syndrome (IHES) and later found to have B-cell ALL with hypereosinophilia. The patient presented with complaints of excessive weight gain, easy fatiguability, stretch marks on the skin, and mild limb pain. Initial blood examinations revealed leucocytosis with eosinophilia and atypical cells. Bone marrow examination and flow cytometry confirmed the diagnosis of B-cell ALL with eosinophilia. For adolescents and young adults with hypereosinophilia, a comprehensive clinical assessment should be conducted. This includes a complete blood count with differential analysis, peripheral blood smear examination, as well as bone marrow aspiration and biopsy. Flow cytometry and cytogenetic studies of the bone marrow are crucial to confirm ALL diagnosis and to identify any associated genetic abnormalities. The most frequently observed genetic abnormality in patients with ALL and hypereosinophilia is the translocation t (5; 14) (q31; q32), which results in the overproduction of interleukin (IL)-3, IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF). This case underscores the importance of maintaining a high level of clinical suspicion and performing a thorough evaluation when managing adolescents and young adults presenting with atypical manifestations of ALL.