Nijmegen breakage syndrome (NBS)

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive syndrome of chromosomal instability mainly characterized by microcephaly at birth, combined immunodeficiency and predisposition to malignancies. Due to a founder mutation in the underlying NBN gene (c.657_661del5) the disease is encountered most frequently among Slavic populations. The principal clinical manifestations of the syndrome are: microcephaly, present at birth and progressive with age, dysmorphic facial features, mild growth retardation, mild-to-moderate intellectual disability, and, in females, hypergonadotropic hypogonadism. Combined cellular and humoral immunodeficiency with recurrent sinopulmonary infections, a strong predisposition to develop malignancies (predominantly of lymphoid origin) and radiosensitivity are other integral manifestations of the syndrome. The NBN gene codes for nibrin which, as part of a DNA repair complex, plays a critical nuclear role wherever double-stranded DNA ends occur, either physiologically or as a result of mutagenic exposure. Laboratory findings include: (1) spontaneous chromosomal breakage in peripheral T lymphocytes with rearrangements preferentially involving chromosomes 7 and 14, (2) sensitivity to ionizing radiation or radiomimetics as demonstrated in vitro by cytogenetic methods or by colony survival assay, (3) radioresistant DNA synthesis, (4) biallelic hypomorphic mutations in the NBN gene, and (5) absence of full-length nibrin protein. Microcephaly and immunodeficiency are common to DNA ligase IV deficiency (LIG4 syndrome) and severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation due to NHEJ1 deficiency (NHEJ1 syndrome). In fact, NBS was most commonly confused with Fanconi anaemia and LIG4 syndrome. Genetic counselling should inform parents of an affected child of the 25% risk for further children to be affected. Prenatal molecular genetic diagnosis is possible if disease-causing mutations in both alleles of the NBN gene are known. No specific therapy is available for NBS, however, hematopoietic stem cell transplantation may be one option for some patients. Prognosis is generally poor due to the extremely high rate of malignancies

Tumor expression of survivin, p53, cyclin D1, osteopontin and fibronectin in predicting the response to neo-adjuvant chemotherapy in children with advanced malignant peripheral nerve sheath tumor

Purpose Selected cell-cycle regulators and extracellular matrix proteins were found to play roles in malignant peripheral nerve sheath tumor (MPNST) biology. We aimed to analyze whether initial tumor tissue expressions of survivin, p53, cyclin D1, osteopontin (OPN) and fibronectin (FN) correlate with the response to neo-adjuvant CHT (naCHT) in children with advanced inoperable MPNST. Methods The study included 26 children with MPNST (M/F 14/12, median age 130 months) treated in Polish centers of pediatric oncology between 1992 and 2013. Tissue expression of markers was studied immunohistochemically in the manually performed tissue microarrays and assessed semi-quantitatively as low and high, based on the rate of positive cells and staining intensity. Results Good response to naCHT was noted in 47.6%, while poor-in 52.4% of patients. The response to naCHT was influenced negatively by the presence of neurofibromatosis NF1 and high initial tumor tissue expression of OPN, survivin, p53 and cyclin D1. Patients with high tumor expression of either OPN, survivin or p53 and those with simultaneous high expression of ≥ 3 of the markers, responded significantly worse to naCHT, than patients, in whom expression of ≤ 2 markers were detected at diagnosis. Nearly, 85% of patients expressing ≥ 3 markers, responded poor to CHT; while 87.5% of children, expressing ≤ 2 markers, were good responders. Conclusion The initial tumor tissue expression of OPN, survivin, p53 and cyclin D1 may serve as markers to predict response to naCHT in pediatric advanced MPNST. Future studies in more numerous group of patients are needed to confirm these preliminary results

Epidemiology and prevention strategies of SARS-CoV-2 infection in pediatric hematology and oncology centers in Poland

IntroductionEpidemiological analysis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections in pediatric hematology and oncology (PHO) and hematopoietic cell transplant (HCT) centers in a Polish nationwide study, as well as analysis of the preventive strategies in these centers. MethodsAll of the 18 PHO/HCT centers participated in eight surveys and questionnaires conducted over the first 5 months of the SARS-CoV-2/coronavirus disease 2019 (COVID-19) pandemic in Poland. Epidemiological data were collected at eight regular time points, and the strategy of preventive management was done once after 4 months of the pandemic. ResultsDuring this analyzed period, eight patients were positive for SARS-CoV-2. The estimated incidence of SARS-CoV-2 positivity in Polish PHO/HCT centers was 0.5%. After exclusion of HCT patients (with one patient being infected), the estimated incidence of SARSCoV-2 positivity was between 0.5 and 0.6%. In all but one case, the course of COVID-19 was asymptomatic or mild, and it was moderate in one case. None of them developed SARS or respiratory insufficiency, none of them required treatment in the intensive care unit (ICU), and no patient died due to SARS-CoV-2 infection. As of July 1, parents staying in the hospital together with their children were regularly tested for the virus in 13 centers. Asymptomatic healthcare personnel were regularly tested for the virus in seven centers. ConclusionsThe estimated incidence of SARS-CoV-2 infection among PHO/HCT patients is lower than in Western Europe; however, these patients cannot be regarded as a low-risk group. The low COVID-19 incidence should be interpreted as a result of strictly and continuously implemented detailed preventive measures in the PHO/HCT wards and in hospitals

Molecular Markers of Pediatric Solid Tumors—Diagnosis, Optimizing Treatments, and Determining Susceptibility: Current State and Future Directions

Advances in molecular technologies, from genomics and transcriptomics to epigenetics, are providing unprecedented insight into the molecular landscape of pediatric tumors. Multi-omics approaches provide an opportunity to identify a wide spectrum of molecular alterations that account for the initiation of the neoplastic process in children, response to treatment and disease progression. The detection of molecular markers is crucial to assist clinicians in accurate tumor diagnosis, risk stratification, disease subtyping, prediction of treatment response, and surveillance, allowing also for personalized cancer management. This review summarizes the most recent developments in genomics research and their relevance to the field of pediatric oncology with the aim of generating an overview of the most important, from the clinical perspective, molecular markers for pediatric solid tumors. We present an overview of the molecular markers selected based on therapeutic protocols, guidelines from international committees and scientific societies, and published data

Molecular Markers of Pediatric Solid Tumors—Diagnosis, Optimizing Treatments, and Determining Susceptibility: Current State and Future Directions

Advances in molecular technologies, from genomics and transcriptomics to epigenetics, are providing unprecedented insight into the molecular landscape of pediatric tumors. Multi-omics approaches provide an opportunity to identify a wide spectrum of molecular alterations that account for the initiation of the neoplastic process in children, response to treatment and disease progression. The detection of molecular markers is crucial to assist clinicians in accurate tumor diagnosis, risk stratification, disease subtyping, prediction of treatment response, and surveillance, allowing also for personalized cancer management. This review summarizes the most recent developments in genomics research and their relevance to the field of pediatric oncology with the aim of generating an overview of the most important, from the clinical perspective, molecular markers for pediatric solid tumors. We present an overview of the molecular markers selected based on therapeutic protocols, guidelines from international committees and scientific societies, and published data

Antineoplastic chemotherapy and congenital tooth abnormalities in children and adolescents

Aim of the study : Chemotherapeutic treatment in children and adolescents carries a risk of congenital tooth disorders and dentinoma. Study objective is to assess the correlation between tooth abnormalities, early complications of multidrug chemotherapy, and chemotherapeutics used in different antineoplastic therapies in children and adolescents. Material and methods : Enamel defects (developmental defects of enamel index – DDE index) and defects in tooth number, size, and structure were assessed clinically and radiologically in 60 patients who underwent chemotherapy on average 4.9 ±3.4 years earlier (PCH), and 60 generally healthy subjects (control group – CG), aged 6–18 years. Höltta’s defect index (DeI) was calculated. Medical files provided information on neoplasm type, age at treatment start and chemotherapy duration, chemotherapeutic type and dose, vomiting, and mucositis (CTCAE v4.0). Statistical significance of differences between groups was assessed with the Mann-Whitney U test and the correlation between dental defects and chemotherapy with Spearman’s rank correlation coefficient (significance p ≤ 0.05). Results: Enamel defects, tooth agenesis, microdontia, root resorption, taurodontism, and dentinoma occurred statistically significantly more often in the PCH group. A correlation was established between vincristine use and dose and all types of dental defects; cyclophosphamide, doxorubicin, and isophosphamide and hypodontia; microdontia, root resorption, and enamel defects; etoposide and cisplatin and microdontia, root resorption, and enamel defects; methotrexate root resorption and enamel defects; carboplatin and dentinoma and enamel defects. Mucositis and vomiting promoted root resorption, microdontia, and enamel defects. Conclusions : Dental defects are related to both the use of respective chemotherapeutics, especially vincristine, cyclophosphamide, doxorubicin, and isophosphamide, and to early complications in multidrug chemotherapy – mucositis and vomiting. Vincristine and carboplatin use may promote dentinoma