Iranian Journal of Pediatric Hematology & Oncology

Plasma Calprotectin Level as a Potential Biomarker in Different Phases of Pediatric Hemato-Oncological Malignancies: A Pilot Study

Bita Bandar — 2024-12-15

Background: Calprotectin has been known as a biomarker for systemic inflammation, especially in autoimmune disorders. Inflammation is a process associated with malignant progression, and calprotectin is a potential prognostic biomarker in some hematologic malignancies. Our pilot study aimed to evaluate the plasma calprotectin level as a promising biomarker in the relapsed/refractory phase of pediatric hemato-oncological malignancies.

Materials and Methods: This pilot research is a case-control study. A total of 168 individuals were included in the study. The analyses were conducted on 73 pediatric patients diagnosed with acute leukemia and 60 others with solid tumor cancers who had referred to Ahvaz Shafa Hospital in Iran. The patients were subdivided based on the three phases of the disease, including on-treatment, relapsed/refractory, and remission phases. Also, 35 healthy children were considered as the control group. After consent was received from all the participants, their blood samples were collected in ethylene diamine tetra acetate (EDTA) tubes to measure plasma calprotectin levels by the enzyme-linked immunosorbent assay (ELISA) method. The data were analyzed using the SPSS26 software. Kruskall-Wallis, Bonferroni Post hoc, and bivariate correlation tests were used, and a two-sided p-value < 0.05 was significant.

Results: There was no statistically significant difference among the plasma calprotectin levels in different phases of acute leukemia (P = 0.099); however, the mean levels of the studied groups were higher than the healthy controls. This increase in the average calprotectin level was also observed in different phases of solid tumor cancers compared to the control group. Besides, a significant difference was seen between the on-treatment and remission groups compared to the control group (p = 0.011 and p = 0.016, respectively).

Conclusion: The mean plasma calprotectin levels increase in different phases of some pediatric hemato-oncological malignancies, but it cannot be used as a specific biomarker for the relapsed/refractory phase.

Impact of Chemotherapy on Echocardiography, Uric acid and Lactate Dehydrogenase in Children with Acute lymphoblastic leukemia (ALL)

Arash Alghasi — 2024-12-15

Background: Acute lymphoblastic leukemia (ALL) is the most prevalent malignancy in pediatrics. ALL blood cancer causes excessive production of immature white blood cells called lymphoblasts or leukemic blasts. Therefore, the present study evaluates the effect of chemotherapy on echocardiography, uric acid (UA) and lactate dehydrogenase (LDH) in ALL children.

Materials and Methods: A quasi-experimental study was designed for 53 ALL patients who referred to Shahid Beqaei 2 in Ahvaz from 2022 to 2023. The inclusion criteria for the studied ALL children aged 2 to 16 years were the maintenance phase of chemotherapy and lack of symptoms of cardiomyopathy. The levels of LDH, UA and echocardiographic parameters were compared before and after chemotherapy through paired sample t-tests. P-values<0.05 were considered significant.

Results: The mean age of the ALL patients was 6.28 ± 4.13 years. Of all the patients, 64% were male. The mean levels of LDH before and after chemotherapy were 1443.36 ± 1373.26 and 534.51 ± 236.61 U/L, and the LDH levels decreased significantly after chemotherapy (P < 0.001). The mean U.A levels before and after chemotherapy were 6.67 ± 6.80 and 5.30 ± 6.15 mg/dl, respectively (P = 0.30). Abnormal echocardiography before and after chemotherapy was observed in 3.76% and 22.64% of the patients, respectively, but the difference was not markedly significant (P = 0.44). The relative risk was estimated to be 0.16, suggesting that the probability of cardiac dysfunction after chemotherapy reduced to approximately 16% of the baseline risk observed before chemotherapy.

Conclusion: The initial evaluation of serum LDH can be beneficial in knowing the response to chemotherapy. So, it is of importance to determine the prognostic value of this biological marker. On the other hand, chemotherapy does not seem to have a significant effect on the mean values of echocardiographic parameters and the level of uric acid.

The Gene Expression Levels of ETS2, ADAM28, and GPRC5D Genes in Acute Lymphoblastic Leukemia Patients

Farnoush Farokhian — 2024-12-15

Background: Genetic biomarkers significantly influence the pathological differentiation and proliferation of lymphoid precursor cells, contributing to the development of Acute Lymphoblastic Leukemia (ALL) in children. This case-control study aimed to assess the expression levels of three potential biomarkers: ETS2, ADAM28, and GPRC5D, in patients with ALL.

Materials and Methods: In this cross-sectional study, a group of ALL patients (n=65) referred to the hematology-oncology departments of Nemazee Hospital and Amir Hospital in Shiraz, Iran, from May 2018 to May 2021 were selected as the patient group. A control group (n=65) of age- and gender-matched volunteers was also selected.

Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to study the expression profiles of these genes in patients and compare the results to those of a control group. The study included 65 patients with ALL and 65 healthy participants. The Pfaffl method of relative quantification, which compares the threshold cycle of a constitutive gene (TBP) with the test gene of each sample in duplicate, was used to determine the relative levels of ETS2, ADAM28, and GPRC5D gene expression. SPSS software version 16 was used for statistical analysis. Nonparametric tests were used to analyze non-normally distributed data, and the Mann-Whitney test was used to compare the medians and ranges and a p-value of 0.05 was considered significant.

Results: The patient group showed significantly greater expression of the ETS2 and ADAM28 genes compared to the control group. (P <0.0001; fold changes of 2.80 and 2.14, respectively), while GPRC5D expression remained unchanged (P >0.05).

Conclusion: These genetic biomarkers in patients with ALL may play an oncogenic role in the pathogenesis of the disease and could serve as potential novel biomarkers for ALL.

Evaluation of Chelidonium Majus L. Alkaloid Effect on VEGF Gene Expression and Cell Apoptosis in the Burkitt Lymphoma Cell Line

Mitra Sadeghpour Natanzi — 2024-12-15

Background: Burkitt lymphoma (BL) is a type of mature B-cell non-Hodgkin’s lymphoma that commonly develops in children and young adults. Vascular endothelial growth factor (VEGF) is acknowledged as a vital regulator of angiogenesis in both normal and disease states. In light of the adverse effects linked to chemical treatments, this study aimed to explore the anticancer effects of Chelidonium majus L. alkaloid on the Daudi BL cell line and to evaluate the expression of the VEGF gene.

Materials and Methods: This project was an experimental study. The cytotoxic effects of the alkaloid derived from Chelidonium majus L. on the Daudi and normal cells were evaluated using MTT assays (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). The induction of apoptosis in cells was measured utilizing Annexin V/propidium iodide (PI) flow cytometry. Additionally, the expression levels of the VEGF gene were determined via a Real-time PCR assay. Data were entered into SPSS, version 21. Student’s t-test and ANOVA test were used for comparisons of groups.

Results: The 50% cytotoxic concentration (CC₅₀) of the alkaloid from Chelidonium majus L. was found to be 56.35µg/mL in the Daudi cell. Findings from flow cytometry aligned with those from MTT assays. Real-time PCR assay results showed a significant decrease in the VEGF gene expression (P<0.009). Effects observed after 48 hours of treatment across various concentrations of Chelidonium majus L. alkaloid demonstrated dose-dependency. However, in peripheral blood mononuclear cells (PBMCs) as a control, the alkaloid did not significantly affect the expression of the VEGF gene (P>0.05).

Conclusion: The alkaloid is derived from Chelidonium majusL. Appears to influence angiogenesis by down-regulating the VEGF gene expression, suggesting its potential as a complementary agent in chemotherapy for Burkitt lymphoma. However; further research is required to evaluate the effectiveness of the Chelidonium majusL. Extract as a definitive treatment for Burkitt lymphoma.

Tropisetron-Induced Apoptosis: A Study on SKOV3 Cell Viability and Gene Expression

Fatemeh Tavakoli — 2024-12-15

Background: Ovarian tumors account for 1% of all childhood neoplasms and are the most common genital neoplasm in children. Considering the role of serotonin in the promotion of tumor growth and metastasis in some cancers, tropisetron as a 5-hydroxytryptamine (5-HT3) receptor antagonist can exert anti-neoplastic effects. The current study seeks to determine the association between the use of tropisetron and ovarian cancercell lines (SKOV3) by evaluating apoptotic regulators.

Materials and Methods: In this experimental study, after the addition of tropisetron to SKOV3 cancer cells at the concentrations of 1, 10, and 100 μM, the MTT assay was employed to assess the cell viability percentage within 24, 48, and 72 hours. The level of expression of Bcl2 and Bax genes after 24 hours were determined by Real Time-PCR, and Caspase 3 enzyme activity was measured by the ELISA method. Differences between groups were statistically analyzed by one-way analysis of variance (ANOVA). A p-value less than 0.05 is considered to be statistically significant.

Results: Based on the MTT test, tropisetron significantly decreased the viability of SKOV3 cancer cells. It decreased the levels of Bcl2 expression according to real-time PCR results (P =0.0015) but increased the expression levels of Bax (P = 0.011) in SKOV3 cells. Both caspase-3 enzyme activity and the ratio of Bax to Bcl2 expression (Bax/Bcl2) were increased (P = 0.008 and P = 0.011, respectively).

Conclusion: Tropisetron could inhibit tumor cell growth via apoptosis induction and exert proapoptotic effects in an ovarian cancer ¬cell line. Therefore, it seems that it can be considered as a possible chemotherapy drug for ovarian cancer. However, more studies should be conducted in this regard.

A Risk-Based Approach to Designing an Academic Research Project: Comparing the Effects of X- and Gamma-Ray Irradiation on the Lymphocytes of Blood Bags

Mahboobeh Shojaei — 2024-12-15

Background: The risk assessment of research projects provides a valuable approach for designing proper methodology, assuring data reliability, and accurately forecasting the resource requirements. Although X-ray irradiation has been globally recognized as a safe method for blood bag sterilization, it has not replaced gamma irradiation in Iran. To facilitate this replacement, a suitable methodology and the assessment of the intervening factors and the risks involved are required. Therefore, this study aims to evaluate the risks associated with X-ray and gamma irradiation using Failure Mode and Effects Analysis (FMEA) as a preliminary model applied in various scientific centers.

Materials and Methods: This interventional study uses FMEA to identify the failure modes in six primary processes. Severity (S), occurrence (O), and detection (D) scores were assigned to each failure mode, and their product, the Risk Priority Number (RPN), was calculated to rank the risk levels and compare the failure modes. Control and preventive measures were defined for the failure modes, and the RPN scores were re-evaluated six months later to assess their effectiveness.

Results: Twenty-two failure modes with RPN scores ranging from 24 to 360 were identified and evaluated. Through defining control and preventive measures for all the analyzed failure modes, the overall risk level was reduced from a baseline RPN of 114.36 ± 94.97 to a re-scored RPN of 12.18 ± 7.64. This represents an approximately 89.45% reduction from the baseline. The reduction in RPN was primarily due to the changes in the occurrence and then detection.

Conclusion: FMEA is a robust tool for analyzing and mitigating risks in research projects, enhancing their quality before implementation. By this method, the risks associated with replacing gamma irradiation with X-ray irradiation for blood bags can be identified and controlled, leading to the elimination of irradiation limitations for blood bags nationwide.

The Survival Rate of Leukemia Patients in Asian Regions: A Systematic Review and Meta-Analysis Study

Reza Zare — 2024-12-15

Background: Leukemia is one of the most common types of cancer worldwide, especially in children. The present research aims to comprehensively estimate leukemia cancer survival in Asian countries through a systematic review and meta-analysis.

Materials and Methods: The current research is a systematic review and meta-analysis of leukemia patients' survival rates in Asian countries. Five databases ISI, PubMed, Scopus, ProQuest, and Google Scholar were used to search for relevant studies. Keywords were selected based on MeSH. The search for studies continued until February 1, 2023. The random-effects model was used to reduce the risk of bias in the studies. The Egger’s regression test was also used to evaluate the risk of publication bias. A total number of 73 papers were considered for the analysis. All analyses were performed by Comprehensive Meta-Analysis Version 2 software.

Results: The overall one-year and five-year survival rates of the leukemia patients were 62.3% (95% CI: 60.9%-63.6%) and 46.7% (95% CI: 41.2%-52.3%), respectively. The results of the subgroup analysis revealed that the five-year survival rate of myeloid leukemia was 36.3% (95% CI: 35.8%-36.8%), while the five-year survival rate of lymphoid leukemia was 62.4% (95% CI: 58.2%-66.4%). The results of the overall 5-year survival rate of leukemia patients by age group showed that, in general, children have a higher survival rate than adults [63.3% (95% CI: 58.7%-67.6%) vs. 27.6% (95% CI: 23.2%-32.6%)].

Conclusion: In general, the survival rates of leukemia patients in Asian countries are very different. On the whole, however, the present study demonstrated that the five-year survival rate for leukemia patients in Asian countries has achieved a level of 46.7%, irrespective of variables such as age, cancer stage, or treatment protocol.

“Think Beyond Trauma!” Multiple Epidural Hematoma in Sickle Cell Disease: A Conundrum

Ruchika Bhatnagar — 2024-12-15

Epidural hematoma is conventionally thought to occur secondary to trauma. Atraumatic/spontaneous epidural hematoma is of rare occurrence and the etiology spans from dural vascular malformations, neoplasms, and coagulopathy to sinus, middle ear, and orbital infections. Occurrence of atraumatic epidural hematoma in sickle cell disease is rarely reported as opposed to frequent neurological complications, such as ischemic stroke seen in 54% of cases, followed by intracerebral, subarachnoid, intraventricular, or subdural hemorrhages. This study reports the case of an eight-year-old male with Sickle cell disease (SCD). He suffered from fever followed by splenic sequestration and multiple spontaneous epidural hematomas without mass effect and successfully managed with conservative treatment.