Iranian Journal of Pediatric Hematology and Oncology
Volume:12 Issue: 3, Summer 2022

Febrile neutropenia (FN) is most often caused due to chemotherapy. Solid or certain lymphoproliferative malignancies can increase the duration of hospitalization and other complications in cancer patients. Filgrastim is used in childhood FN management. This study aimed to compare the effect of two different doses of Filgrastim on hematological and paraclinical factors in hospitalized febrile neutropenic patients with cancer. 

In this randomized clinical trial, 60 febrile neutropenic patients with cancer complying with the inclusion criteria were assigned to both groups A and B. Thirty patients in group A received Filgrastim 5μg/kg/day whereas 30 others in group B received Filgrastim 15μg/kg/day. Hematological factors, physical examination findings, antibiotic administration period, and type of malignancy were then recorded. Complete blood count with differential (CBC diff) was also tested. Lung infiltration was examined by chest X-ray (CXR), and the spleen and abdomen were monitored by ultrasound.

The mean age of patients was 6 ± 3 years old. The most prevalent malignancies included acute lymphoblastic leukemia (ALL) (35.0%), neuroblastoma (18.3%), osteosarcoma (11.7%), acute myeloid leukemia (AML) (8.3%), and Rhabdomyosarcoma (8.3%). The frequency distribution of malignancies significantly differed between the two groups (P= .01). Changes in hematological factors, including white blood cells (WBC), mature neutrophil cells, and absolute neutrophil count (ANC) in group A, appeared lower than those in the other group. However, none of the studied factors, including hematological factors, physical examination findings, and antibiotic administration period, were found to differ significantly between the two groups (P> 0.05).

Much as a higher dose of Filgrastim seems to bear a better effect on ANC, no significant difference was identified between the two groups. Further studies should be designed with a larger population to address the issue.

In various cancers, Ganoderic Acid A (GAA), an active triterpenoid derived from Ganoderma lucidum, has been proved to show potent anti-tumor effects. However, the possible impacts of GAA on the human leukemia cell line (Nalm-6) are not fully elucidated. Therefore, this research aimed to study the antineoplastic effect of GAA on Nalm-6 cells.

In this laboratory trial study, Nalm6 cells were cultured in vitro and treated with different doses of GAA (25, 50, 100, 200, and 400 μg/mL) for 24, 48, and 72 hours. The optimal treatment concentration of GAA was determined by the MTT assay. Flow cytometry was used to determine the death of Nalm-6 cells caused by GAA treatment by utilizing FITC-conjugated propidium iodide (PI) and annexin V staining. After incubation, the expression levels of miR-17-5p and miR-181b were monitored using real-time polymerase chain reaction (PCR).

Based on the half-maximal inhibitory concentration (IC50) measurements of the MTT assay, the optimal treatment concentration of GAA was 140 μg/mL (in a dose and time-dependent manner, p<0.0001). The GAA treatment was selectively toxic to the leukemia Nalm-6 cells and could remarkably induce cell apoptosis (p<0.0001). Besides, GAA downregulated the expression of miR-17-5p and miR-181b in the Nalm-6 cells compared with the untreated cells (P=0.0067 and P=0.0014, respectively).

Based on the present findings, GAA merits further investigation as a promising natural reagent for treating hematologic malignancies.

This study aimed to assess the frequency determination of c.1115_1118delTTGG and c.3788_3790delTCT Fanconi's anemia A gene (FANCA) gene mutation in the North of Khyber Pakhtunkhwa (KPK) Pakistan Fanconi’s Anemia Population.

A cross-sectional study was conducted at Khyber Medical University, Peshawar, Pakistan. For the Exon 13 mutation c.1115_1118delTTGG, the amplification-refractory mutation system polymerase chain reaction (ARMS PCR) was developed. Sanger sequencing confirmed the ARMS PCR results for Exon 13 and found an exon 38 mutation of the FANCA (Fanconi anemia complementation group A) gene (c.3788_3790delTCT). Sanger sequencing results analyzed on Bio edit sequence aligner software confirmed the results of PCR. The four incidental single nucleotide polymorphisms (SNPs) discovered were examined in several variation databases.

 The mean age for the patients was 9.68±3.02 years, with an age range of 5–16 years. Pedigree analysis of Fanconi Anemia patients revealed an autosomal recessive pattern of inheritance. Physical characteristics such as skeletal abnormalities, specifically thumb abnormalities and Fanconi's facies, are distinctive diagnostic features of FA. Pedigrees also showed bone marrow hypoplasia in 65% of patients and red cell aplasia in 6%. PCR results from all samples revealed tahat none of them had the Exon 13 mutation. In addition, none of the samples had the Exon 38 mutation. Four SNPs were found in the Sanger sequencing. Two of them were in the intron 12 region, one in each of Exons 13 and 38.

Results show that mutations in Exon 13 and Exon 38 of the FANCA gene are uncommon in our Pakistani FA population. SNPs established in the Pakistani population of Khyber Pakhtunkhwa (KPK) province have not been reported before.

Early diagnosis of neonatal sepsis is quite challenging. I/T ratio (immature to mature neutrophil ratio) is a highly sensitive marker of sepsis but is time-consuming and subjective. Off late, volume conductivity and scatter (VCS) of neutrophils are among the newer parameters available for screening a septic neonate. This study aimed to determine the correlation between the I/T ratio and VCS parameters in neonatal sepsis and estimate a cut-off value of VCS parameters to diagnose neonatal sepsis using receiver operating curve analysis.

This prospective observational study was conducted by the Department of Pathology and Neonatology from April 2019 to March 2020 in a tertiary care center. A total of 110 newborns were included in this study and were divided into two groups (probable sepsis and sepsis). Data were collected from the hospital database, and analysis was done using SPSS software. Correlation between the I/T ratio and VCS parameters was done using Spearman’s correlation. Results were expressed as mean ± standard deviation (SD). A P-value of <0.05 was considered statistically significant. 

Correlation between the I /T ratio and VCS parameters showed negative correlation values of -0.22, -0.23, and +0.39 (P-values of 0.0198, 0.0153, and <0.0001) for mean neutrophil conductivity (MNC), mean neutrophil scatter (MNS) and mean neutrophil volume (MNV) respectively. MNV with a cut-off of > 156.4 had sensitivity and a negative predictive value of 100 % in the diagnosis of sepsis and was found to be higher in the sepsis group when compared to the probable sepsis group.

Based on the significant difference in VCS parameters of neutrophils in the sepsis group, this aids as an additional marker for the early diagnosis of neonatal sepsis.

The role of phosphate hemostasis in development of thalassemia bone disease has not been extensively studied yet. Due to the lack of sufficient human studies about the changes of serum Fibroblast growth factor-23(FGF23) in patients with beta-thalassemia major as the first step of investigating the role of FGF23 in thalassemia bone disease, the present study aimed to investigate the serum level of FGF23 in patients with thalassemia major.

In this case-control study, 25 patients with beta thalassemia major and their age- and sex-matched healthy volunteers were enrolled. Serum phosphorous, calcium, parathyroid hormone (PTH), 25(OH) D, erythropoietin (EPO), serum intact FGF23 (iFGF23) and 1,25 (OH)2 D were checked and analyzed.

Patients with beta-thalassemia major had lower 1,25 (OH)2D, (p = 0.025), higher phosphate (p = 0.002), and higher PTH (P <0.001) compared to the control group; however, all of them were in their normal blood range. They also had higher serum FGF23 (p = 0.007) and higher EPO (P<0.001). Serum FGF23 had an independent association with serum Iron (p=0.016), 1, 25(OH)2 Vitamin D (p<0.001), and hemoglobin (p=0.002).

Serum FGF23 was associated with serum Iron, 1, 25(OH)2 Vitamin D, and hemoglobin in beta-thalassemia major patients. Hence, it seems that regular transfusions and chelating agents which can decrease the serum iron and increase hemoglobin level can be associated with lower iFGF23.

In various cancers, Ganoderic Acid A (GAA), an active triterpenoid derived from Ganoderma

Thalassemia refers to a category of inherited disorders resulting from defects in synthesizing one or several chains of hemoglobin (Hb). The present study aimed to determine the frequency of alpha and beta-thalassemia mutations in Kurdistan province, Iran.

In this retrospective cross-sectional study, the laboratory data of 340 patients with thalassemia (170 females and 170 males), who were candidates for genetic testing in Kurdistan province, were examined over ten years (2006-2016). The participants were Kurd couples selected from the premarital health screening program.

In this demographic study, 20 beta mutations and nine alpha mutations were identified. Among the beta-thalassemia mutations, intervening sequence or intron No. 2- first nucleotide change as splice site mutation (IVS-II-1) (26.1%), codons 8/9 (14.8%), and intervening sequence or intron No. 1- first nucleotide (IVS-I-1) (12.2%) change as splice site mutation), had the highest frequency rates, respectively, constituting 53% of the beta mutations. In addition, α3.7(82.7%), -α4.2(8.3%), and --MED (Mediterranean deletion) (3.75%) were the most frequent alpha mutations, which constituted more than 90% of the alpha mutations.

According to the results, the most frequent mutations in the HBB gene are IVS-II-1, Codons 8/9, and IVS-I-1, and in the HBA gene are α3.7, -α4.2, and –MED in Kurdistan province. In addition, the role of race and ethnicity as significant, influential factors in thalassemia was observable in the findings. The obtained results also indicated the communication pattern between the studied region's populations. Identifying common thalassemia mutations in an area could greatly benefit the early detection of thalassemia carriers in genetic laboratories and enhance thalassemia prevention programs.

Inflammation plays a critical role in the progression of cancer in children. On the other hand, children with cancer experience abnormal activation of the inflammatory system. Moreover, it is known that these patients have a predisposition to depression. According to studies, moderate to severe depression was observed in about 63% of children with cancer and acute illness. Therefore, identifying inflammation-related biomarkers and targets in this regard is essential. The inflammation changes are related to cytokine deregulation, which in turn may influence the expression of depressive symptoms. Studies have reported that the deregulation of serum inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α may influence depressive disorder in pediatric cancer patients.  In addition, determining the risk of severe bacterial infection complications in pediatric cancer is essential to reduce the cost of therapy and hospitalization. However, the role of cytokines as an infection marker in these children is still a debate. Determining these plasma cytokine levels may have diagnostic value in assessing febrile neutropenia, although their crucial role in systemic inflammation is known. Given that evidence regarding the role of pro-inflammatory cytokine levels and relation to clinical parameters, including depression and infection in pediatric cancer patients is limited, we assessed the role of cytokine and its relation to depression and infection complications in pediatric cancer.

Neuroblastoma (NB) is considered one of the malignant tumors of the nervous system which originates from primordial neural crest cell and is known as the most common extra-cranial solid tumor in childhood. This tumor which is often intra-abdominal, metastases in various sites including the skull, long bones, liver, bone marrow and lymph nodes, but lung metastasis at initial diagnosis is rare (0.2-3.7%). Here, the authors reported a two-year-old boy who referred to Imam Hussein Children's Hospital affiliated to Isfahan University of Medical Sciences, Iran in April 2017 with complaint of abdominal pain and distension along with diarrhea, vomiting and fever. In physical examination, a palpable mass was observed at the right side of the abdomen, that in further studies, NB with lung metastasis along with poorly differentiated, low MKI, positive MYCN amplification was reported. This is the first documented case report of NB with lung metastasis from Iran. In conclusion, although lung is considered as an unfavorable metastatic site for NB, in high grade and poor prognosis cases, this organ should also be examined in metastatic site examinations. Therefore, lung High-resolution computed tomography (HRCT) is introduced as the gold standard modality for this work.