Vol 16, No 4 (2017)

Acute lymphoblastic leukemia (ALL) is the most common oncological disease of childhood. With modern approaches to therapy, approximately 85% of patients with ALL can be considered recovered. However, treatment of relapses and resistant forms of the disease remains a problem. Carrying out high-dosage chemotherapy with subsequent allogeneic TSCS is considered the standard of therapy for such patients. But this is not always effective and, as a rule, is associated with severe concomitant complications. The use of immunotherapy – blinatumomab, a bispecific antibody that allows the patient's own cytotoxic lymphocytes to recognize and destroy leukemia cells, allows achieving full-fledged MRD-negative remission, like a bridge to the TSCC. The effectiveness of blinatumomab probably depends on the composition of the patient's lymphocytes, the presence of CD19 on tumor cells, the number of blast cells in the patient. The article presents own data on the use of blinatumomab in a cohort of patients with refractory and recurrent forms of B-linear ALL and a literature review. The study included 14 patients with refractory ALL from B-progenitors. The median age was 9 years. 8 patients had more than 5% of blasts in the myelogram at the time of onset of therapy with blinatumomab. Blinatumomab was administered at standard dosages in a 28-day continuous infusion. The progression was noted in 1 patient after TSCC and in 2 after HT, all had ≥ 30% of blasts before blinatumomab. The remaining 12 children achieved MRD-negative remission, 11 of them received haploBMT. Of the toxic effects, fever was observed in 80% of cases, 1 case of tremor and 1 case of convulsions. The first Russian experience with the use of blinatumomab in pediatric patients with refractory forms of ALL has proven to be quite successful and may be the basis for subsequent controlled studies both in patients with relapses and, possibly, in some groups of primary diagnosed ALL.

Blinatumomab is a bispecific T-cell engager (BiTE) antibody construct targeting CD3 and CD19, resulting in T-cell-mediated lysis of malignant B cells. CD19 downexpression is shown to be one of the possible mechanisms of tumor cells adaptation and subsequent escape from treatment. The aim of the present study was to evaluate changes of CD19 expression on residual tumor cells in children with BCP-ALL treated with blinatumomab. 39 patients with relapsed/refractory BCP-ALL who completed at least one course of blinatumomab, were studied. MRD monitoring was performed by 8-color flow cytometry. In those children, who didn’t respond and/or developed subsequent relapse, CD19 downexpression seems to be one of the significant pathways for tumor escape from blinatumomab – 50% of relapses were CD19-negative, and in 26.3% of all relapsed/resistant cases CD19-negative blasts were detected at least on MRD level. Rather frequent loss of CD19 could be a serious obstacle for flow cytometric MRD monitoring, but application of expanded antibodies panel and use of 10–12-color investigation allows residual blasts detection in nearly all cases.

Hereditary angioedema (HAE) is a rare disease with autosomal dominant inheritance predominantly caused by decrease of C1 inhibitor level and/or function as a result of SERPING1 (C1NH) gene mutations. HAE patients develop edema of variable severity and localization, often life-threatening. The data on correlation of SERPING1 defects and HAE clinical course is conflicting. Aim: To study the variability of genetic defects in HAE, their correlation with the severity of disease symptoms. The study group included 69 HAE patients from 30 families, as well as seven symptoms-free mutation carriers (all children). Mutations were assayed via direct sequencing and MLPA method. The patients were divided in two groups depending on the type of the mutation: group one included patients with potentially deleterious mutations (including the functional center R466C), the second – with less deleterious (missense) mutations, excluding R466C. We identified 27 different mutations, 11 have not been described previously. Exon 7 contained the most of them. We found a large proportion (5 out of 27) of large deletions. When disease severity was compared in two groups of patients we found it to be higher in the first group (Ме – 7 in the first group, Ме – 5 in the second, р = 0.03). Though clinical and laboratory data is enough to make the HAE diagnosis, molecular genetic testing is important for patients with HAE type 1 and 2, as well as for their symptoms-free relatives, as it allows an early diagnosis and prediction of the disease severity and a timely start of the targeted therapy.

This review article deals with the histological and molecular diagnosis of thalamic glioblastomas in children, authors discuss the need of new approaches to the treatment of such tumors.

The development of the tumor process and chemotherapy with its after-effects, can cause nutritional disorders that aggravate the course of the disease and complicate recovery of patient. It is very important to choose the right type of nutritional support (parenteral or enteral nutrition). The aim of the study was to determine changes in the nutritional status of children with non-Hodgkin's lymphomas (NHL), its effect on the duration of aplasia and development severe complications in the active treatment process and to assess the impact of different types of nutritional support on these parameters. The retrospective study with a comparative analysis was performed. It included 54 patients, including 40 (74%) boys, aged 1–17 years (median – 9 years). We analyzed anthropometric parameters – body mass index (BMI), triceps skinfold thickness (TSF), mid-upper arm muscle circumference (MUAMC) – on five periods of time respective to the course of therapy: "0" – 1–3 days before the beginning of cytoreductive phase of treatment; "1, 2, 3, 4" – the last day of the therapy and 4 days after it. The reliable positive dynamics of TSF during monitoring period was found (p < 0.05), it was more pronounced in patients with initial nutritional insufficiency (p < 0.05). It was associated with a greater incidence of severe complications (p = 0.02). Comparative analysis of types of nutritional support showed that the most effective is combination of enteral and parenteral nutrition, although the latest is associated with a greater frequency of nephro- and hepatotoxicity.

Kabuki syndrome (KS) is a rare inherited disease that consists of a specific morphological changes in the face, short stature, various organ malformations, variable degree of intellectual disability. Mutations in KMT2D gene have been identified as the main cause for KS type 1 (KS type 1 about 70% of patients), whereas mutations in KDM6A gene causes KS type 2 are a much less frequent (less than 5% of patients). Most mutations of KMT2D are private de novo mutations; familial occurrence with an autosomal dominant pattern has also been reported. KS type 2 (caused by mutations in a second gene, KDM6A) has X-linked inheritance. Both genes functioning as epigenetic modulators through histone modifications in the course of embryogenesis and in several biological processes. Different human disorders are caused by mutations of genes involved in the epigenetic regulation, all these share developmental defects, disturbed growth, multiple congenital organ malformations, and also hematological and immunological defects. In particular, most KS patients show increased susceptibility to infections and have reduced serum immunoglobulin levels, while some suffer also from autoimmune manifestations, such as idiopathic thrombocytopenic purpura, hemolytic anemia and other. This article provides a review of the literature and a description of the case report of a patient with genetically confirmed KS type 2, with characteristic phenotypic manifestations, congenital malformations, immunodeficiency and autoimmune cytopenias.

An imbalance in the synthesis and ratio of α and non-α globin chains is the major pathophysiological mechanism leading to ineffective erythropoiesis and hemolysis in severe form of the β-thalassemia. Phenotype in patients who retain the capacity to synthesize fetal hemoglobin (HbF) is milder due to decreasing α- /non-α globin chain imbalance. Induction of HbF might be an effective therapeutic strategy for severe form of β-thalassemia. This literature review presents data about efficiency safeness of different medication and their combination, which stimulate synthesis of HbF. This review can provide a new insight into the current status and future perspectives in HbF reactivation as treatment option for severe form of β-thalassemia.

In the review of the literature, the authors described in detail modern concepts of the structure and functions of telomeres, telomerase and shelterin complexes. The article contains an overview of the data and published to date the results of a study of telomere length in healthy children of different ages, the relationship between body length and certain diseases, as well as the influence of a number physiological factors on the length of children telomere.