Outcomes of pediatric extracranial germ cell tumors: A single center experience in a developing country.

The purpose of this study was to analyze the outcomes of extracranial GCT in children in a developing country and to assess prognostic factors. The data on 141 children (<18 years old) with extracranial GCT, confirmed histopathologically, collected over the past 9 years (from February 2013 to June 2022) were retrospectively studied. The patients underwent the same therapy with platinum-containing chemotherapy regimens. In the malignant GCT group, OS and EFS were 81.0 ± 4% and 73 ± 5%, respectively. OS and EFS in the teratoma group were 90 ± 5% and 85 ± 6%. In univariate analysis, parameters like stage of disease, tumor localization, AFP level ≥10,000 ng/mL, serum AFP kinetics and resection status were found to be statistically significant prognostic factors. In the multivariate analysis, the significant adverse factors were the resection status, initial AFP level ≥10,000 ng/mL and serum AFP kinetics slow down (p = .000). Good survival rates can be achieved in developing countries with adequate compliance with treatment protocols. The analysis demonstrates high efficacy of platinum-containing chemotherapy regimens. In our opinion, the protocol used in high-income countries can be implemented in low-income countries with the financial support from the government. The qualification of specialists is also important.

Long-term outcomes and immune profiling in children with multisystem inflammatory syndrome (MIS-C).

BACKGROUND AND AIM: Existing follow-up data after MIS-C is limited. PURPOSE OF THE STUDY: to investigate the long-term consequences in children who have undergone MIS-C. METHODS: The retrospective study included 93 children. The identified changes were divided into the following periods: occurred within first 6 months, 1 year, 2 years, and more than 2 years after MIS-C. Besides, 31 children underwent prospective immunophenotyping of peripheral blood and the determination of cytokines during the acute period of the disease and after discharge. RESULTS: Outpatient monitoring events included pneumonia (9.6%), somatic disorder syndrome (11.8%), visual impairment (7.5%), joint damage (6.6%), weight changes (2.2%), and MIS-C recurrence (2.2%). A study of the cardiovascular system showed a statistically significant decrease in the frequency of the right and left heart dilatation, left ventricular dysfunction, pericarditis, pulmonary arterial hypertension, coronaritis, mitral regurgitation. But at the same time an increase in pulmonary and tricuspid valve regurgitation and arrhythmias compared with the acute period was detected. Most of the changes took place within first year of observation. Immune profiling showed reconstitution of CD3, CD4 T-lymphocytes, NK-cells, maintenance of a high relative value of CD8, reduction of CD19+ B-cells, expression of CD3-HLA-DR+, CD25, CD279, CD95. CONCLUSIONS: After the history of MIS-C, children in the long-term follow-up had various somatic disorders and disease recurrence. Most patients (64.1%) showed subclinical signs of myocardial involvement within first year of observation. Low expression of CD95 may justify an certain role in the pathogenesis of the disease.

Genes of Predisposition to Childhood Beta-Cell Acute Lymphoblastic Leukemia in the Kazakh Population.

BACKGROUND: Today, acute lymphoblastic leukemia is one of the most common malignant diseases of the hematopoietic system. The genetic predisposition to ALL is not fully explored in various ethnic populations. OBJECTIVE: The study aimed to conduct a comparative analysis of the population frequencies of alleles and genotypes of polymorphic gene variants: immune regulation GATA3 (rs3824662); transcription and differentiation of B cells: ARID5B (rs7089424, rs10740055), IKZF1 (rs4132601); differentiation of hematopoietic cells: PIP4K2A (rs7088318); apoptosis: CEBPE (rs2239633), tumor suppressors: CDKN2A (rs3731249), TP53 (rs1042522); carcinogen metabolism: CBR3 (rs1056892), CYP1A1 (rs104894, rs4646903), according to genome-wide association studies analyses associated with the risk of developing pediatric beta-cell acute lymphoblastic leukemia (B-cell ALL), in an ethnically homogeneous population of Kazakhs with studied populations. METHODS: The genomic database consists of 1800 conditionally healthy persons of Kazakh nationality, genotyped using OmniChip 2.5-8 Illumina chips at the deCODE genetics as part of the InterPregGen 7 project of the European Union (EU) framework program under Grant Agreement No. 282540. RESULTS: High population frequencies of single nucleotide polymorphism (SNP) minor alleles identified for immune regulation genes - GATA3 rs3824662 - 42.5%; transcription and differentiation of B-cells genes - ARID5B rs7089424 - 33.1% and rs10740055 - 48.5%, which suggests their significant genetic contribution to the risk of development and prognosis of the effectiveness of B-cell ALL therapy in the Kazakh population. The significantly lower population frequency of the minor allele G rs1056892 CBR3 gene - 38.6% in the Kazakhs suggests its significant protective effect in reducing the risk of childhood B-cell ALL and the smaller number of cardiac complications after anthracycline therapy. CONCLUSION: The obtained results will serve as a basis for developing effective methods for predicting the risk of development, early diagnosis, and effectiveness of treatment of B-cell ALL in children.

Comparative Analysis of Clinical and Laboratory Data in Children with Multisystem Inflammatory Syndrome Associated with SARS-CoV-2 in the Republic of Kazakhstan.

Background and Objectives: Data with more severe mutations of the SARS-CoV-2 virus, compared with the original wild-type strain of COVID-19 disease, were reported worldwide. The study aims to describe the clinical and laboratory manifestations of a multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 in the Republic of Kazakhstan and to compare the severity of the disease depending on the time of the circulating variant of SARS-CoV-2 virus. Material and methods: A retrospective, multicentre, nationwide study of 89 children with MIS-C who received inpatient treatment from August 1, 2020, to December 1, 2021. The patients were allocated into two groups: 1(2020) - 45 children and 2 (2021) - 44 children. Study periods were characterized by the circulation of different strains of the SARS-CoV-2 virus. Results: In children with MIS-C in 2021, acute renal failure, disseminated intravascular coagulation syndrome, and shock were statistically more frequently found, which led to fairly common admittance to the intensive care unit. When comparing laboratory data, the children with MIS-C in 2021 had higher values of inflammation markers: ferritin, procalcitonin, erythrocyte sedimentation rate, leukocytes, and neutrophils. Furthermore, these children had a lower level of lymphocytes than children with MIS-C in 2020. Conclusions: MIS-C is a severe, life-threatening systemic disease characterized by multiple organ damage and important inflammatory changes in laboratory parameters. A more aggressive clinical course of MIS-C in 2021 may be associated with the emergence of new SARS-CoV-2 strains.