Introduction. The results of treatment of high-risk neuroblastoma (NB) patients at the current stage remain unsatisfactory and overall survival does not exceed 50–60 %. Response to induction therapy, including response from distant metastases, is an important prognostic factor. Worse treatment outcomes are noted in patients who have not achieved complete resolution of metastatic foci. Intensification of postconsolidation therapy with the addition of cytostatic drugs not used at the induction treatment stage to 13-cis-retinoic acid (13-cis-RA) is a possible treatment option aimed at overcoming tumor cell resistance and improving both objective response and long-term prognosis in these patients.

Materials and methods. We conducted a multicenter prospective study of the use of 12 courses of temozolomide in combination with 9 courses of 13-cis-RA as part of postconsolidation therapy in high-risk NB patients who achieved an unsatisfactory response to induction therapy (persistence of metastatic foci) within the modified protocol of German Society for Pediatric Oncology and Hematology GPOH NB-2004, who received this therapy from January 2020 to January 2022. Temozolomide therapy was administered at a dosage of 150 mg/m²/day per os (intravenous administration was allowed) for 5 days and started on day 29 of the first cycle of 13-cis-RA. Another course of 13-cisRA was started on day 6 of temozolomide administration. During the 3-month break between the courses of 13-cis-RA (6 and 7 courses), temozolomide was continued for 5 days (the courses were repeated every 28 days).

Results. Fourteen high-risk NB patients with a median age at the time of diagnosis of 62 months (range – 9–173 months) were included in the study. Thirteen patients with newly diagnosed NB were verified with INSS stage 4 disease and INRGSS stage M; 1 patient with initial localized low-risk NB subsequently developed a combined relapse. 9/14 (64 %) patients received standard induction therapy and 5/14 (36 %) received intensified therapy due to an unfavorable response to the first six courses of induction chemotherapy. The response after completion of induction therapy was evaluated as partial response (PR) in 6/14 patients, mixed response (MR) in 6/14, and stable disease (SD) in 2/14. All patients received high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HSCT) during the consolidation phase. Postconsolidation therapy included a total of 134 cycles of temozolomide. Postconsolidation therapy including 12 cycles of temozolomide was completed by 10/14 (71 %) patients. 4/14 (28 %) patients did not complete therapy (2/4 – parental refusal of therapy and 2/4 – progression (PR)). 4/14 (29 %) patients included in the study fully completed the proposed regimen of post-consolidation therapy (13-cis-RA and temozolomide) without the addition of other therapeutic agents. 6/14 (43 %) patients received all 12 courses of temozolomide in combination with anti-GD2 targeted monoclonal antibodies (mAbs) immunotherapy and/or molecularly targeted therapy. In 3/14 (21 %) patients, manifestations of hematologic toxicity were observed, requiring reduction of temozolomide dosage and increasing the course interval. One out of 3 patients experienced thrombocytopenia on courses 2–5 and 2 out of 3 patients experienced grade II–III neutropenia on courses 5 and 2, 6, respectively. No unexpected serious toxicities, including deaths, were reported during all courses evaluated. Overall, 11/14 (79 %) patients completed first-line therapy (complete response (CR) – 2/11, PR – 7/11, SD – 1/11, PR – 1/11), 3/14 (21 %) did not complete due to disease progression. Currently, 11/14 (79 %) patients are alive (3/11 – after PR/relapse and 8/11 – alive without events). 2/14 (14 %) patients died from disease progression, 1/14 (7 %) – from non-tumor related causes. Median follow-up from diagnosis was 39.3 months for all patients (range – 12.5–62.5) and 42.5 months for survivors (range – 24.4–62.5).

Conclusions. For high-risk NB patients who have not achieved a complete metastatic response to the induction therapy phase, intensification of the postconsolidation phase of treatment may be suggested. The addition of temozolomide to the differentiation agent 13-cis-RA in our study demonstrated minimal toxicity, good tolerability, and improved response in a subset of patients. Further studies are needed to select the optimal regimen of postconsolidation therapy for patients with an unsatisfactory response to the induction phase.

Relevance. Relapses and refractory course (r/r) develop in 10 % of children and adolescents with a newly diagnosed classical Hodgkin lymphoma (cHL). The basis for successful treatment of r/r cHL is morpho-immunohistochemical diagnostics and positron emission tomography, as well as the inclusion of targeted and immune drugs in the treatment regimen. Russian experience of intercenter interaction in the treatment of r/r cHL is small, so each new study is significant from a scientific and practical standpoint.

The aim of the study is to present long-term results of r/r cHL treatment using targeted drugs, chemotherapy and autologous hematopoietic stem cell transplantation.

Materials and methods. From 2003 to 2023, 73 patients with r/r cHL were included in the study. The age of the patients ranged from 5.5 to 18.6 years (median – 14.5 years). Second-line therapy was carried out according to the following regimens: ICE (n = 23; 31.5 %), ViGePP (n = 15; 20.5 %), DHAP (n = 6; 8.2 %), IEP/ABVD (n = 6; 8.2 %); 7 (9.6 %) patients underwent a change in treatment regimen due to a poor response to the first 2 courses of therapy. Sixteen (21.9 %) patients were treated according to the ViGePP regimen with the addition of brentuximab vedotin (6 injections).

Results. The 10-year overall survival of patients was 76 ± 6 %, relapse-free survival (RFS) was 64 ± 6 %. When brentuximab vedotin was included in the therapy program, the RFS was higher – 83 ± 15.2 % (p = 0.09).

Conclusion. The results of a joint cooperative study of two Russian clinics for the treatment of r/r cHL are presented. The data obtained allow us to state the high efficiency of second-line therapy regimens with brentuximab vedotin and subsequent autologous stem cell transplantation.

Introduction. The activity of the enzyme of the second phase of xenobiotic detoxification N-acetyltransferase 2 (NAT2) depends on gene polymorphisms, the presence of which is associated not only with the pharmacokinetics of drugs, but also with susceptibility to diseases. There are ethnic features in the distribution of genotypes of single nucleotide polymorphisms (SNPs) of these genes.

Purpose of the study – to determine the structure of the child population of the Irkutsk region according to the type of acetylation of organic compounds and to study the association between the rate of acetylation and the predisposition to the development of leukemia in children.

Materials and methods. 82 children with acute lymphoblastic leukemia and 250 healthy medical college students belonging to the Russian ethnic group were examined. The average age of patients was 5.59 ± 4.57, in the control group – 19.7 ± 1.4 years. The type of acetylation was determined by genotyping SNP rs1495741 of the NAT2 gene by conducting a polymerase chain reaction in real time. The type of acetylation was determined at the Institute of Biomedical Technologies of IGMU. The material for the study is DNA obtained by scraping the buccal epithelium.

Results. In the group of children with leukemia, the frequency of the genotype associated with slow acetylation prevailed and amounted to 53.66 %, patients with intermediate acetylation – 35.37 %, and with the fast type of acetylation – 10.97 %. In the control group, the frequency of the genotype associated with slow acetylation also prevailed and amounted to 56.4 %. The frequency of intermediate acetylation was 38 %, fast – 5.6 %. No deviations in the distribution of genotype frequencies from the expected according to the Hardy–Weinberg distribution were detected (p > 0.05). Based on the results of calculating the odds ratio according to three models of inheritance, no statistically significant results were obtained and no associative relationship was identified between the rate of acetylation of xenobiotics and the development of leukemia in children. When comparing the frequency of prevalence of acetylation types among the control group of this study and adults examined in Eastern Siberia earlier, a predominance of the slow type of acetylation was revealed both among adults and among children (63 % and 56.4 %, respectively), and the fastest type was the rarest: 6 % and 5.6 %, respectively.

Conclusion. Types of acetylation do not affect the risk of developing leukemia and occur with the same frequency in comparison with the population of healthy representatives of the European ethnic group of the East Siberian region. In children with leukemia and in healthy controls, the frequency of the SNP rs1495741 NAT2 allele, corresponding to slow acetylators, is predominant. There is no associative relationship between the rate of acetylation of xenobiotics and the risk of developing leukemia in children. The revealed pharmacogenetic features in healthy residents of the East Siberian region and patients with acute lymphoblastic leukemia should be taken into account when developing preventive and personalized methods of modern medicine.

Relevance. Early diagnosis of acute leukemia (AL) in children is difficult due to the non-specificity of the symptoms of the onset of the disease, so knowledge of the probable symptoms will allow the doctor to diagnose leukemia earlier, thereby improving the prognosis for the patient.

The aim of the study – is to increase the oncological alertness of health workers providing primary health care to the child population, to update the “clinical and hematological portrait” (the most common clinical and hematological signs) of the manifestation of AL in children.

Materials and methods. The article presents data from a retrospective study of 39 cases of AL in children hospitalized from 2016 to 2022 in the oncohematology department of the Republican Children’s Clinical Hospital in Syktyvkar. Clinical and laboratory data of patients were evaluated in comparison with world literature data.

Results. The prevalence of AL in the Komi Republic was 3.15 per 100,000 children. The study group was dominated by children from urban areas (77 %), males (66.6 %), the median age was 5 years 3 months (min–max – 5 months – 17 years 9 months). At the onset of clinical manifestations, the most common were hyperplastic (97.4 %), infectious (79.4 %), intoxication (46.1 %) syndromes. In the structure of symptoms at the onset of the disease, fever (69.2 %), pain of various localizations (43.5 %), symptoms of local infections (20.5 %) prevailed. In the analysis of laboratory data, absolute neutropenia (76.9 %) was noted with 38.4 % of leukopenia cases. Also, the most frequent hematological changes were thrombocytopenia (87.1 %), anemia (76.9 %) and increased erythrocyte sedimentation rate (87.1 %). In our study, the data comparable with the results of published studies in the world literature were the age of the debut of AL in children, the average duration of symptoms before diagnosis and the leading clinical syndrome – hyperplastic, as well as fever. In the studied cohort, hepatomegaly and splenomegaly as symptoms of hyperplastic syndrome were noted in a greater number of cases, and among the hematological changes, leukopenia demonstrated predominant values, in contrast to the literature data. For the first time, priapism was noted as a symptom of AL in a child in the age group of 13 years.

Conclusion. Our analysis of clinical and hematological data of the debut of AL demonstrates pronounced clinical polymorphism, with a predominance of such symptoms as fever, pain, symptoms of local infectious processes and their combination. Emphasis is placed on the need to assess absolute values of differential white blood cell count in the routine practice of physicians providing primary health care to children. The results obtained draw the attention of primary care pediatricians to the importance of oncological alertness and early detection of AL.

Trilateral retinoblastoma (TRb) phenomenon is a combination of bilateral retinoblastoma (Rb) (in most cases) and molecular group A pineoblastoma (Pb).

The study of this phenomenon has been going on for more than 30 years, is interdisciplinary in nature and includes two conceptual points of view from the positions of ophthalmic oncology and neurooncology.

The frequency of this phenomenon detection varies from 0.75 to 2 % in the entire research group and from 2.1 to 3.5 % in the structure of bilateral forms. Intraocular lesions were presented by a bilateral variant in 91.5 % of clinical cases. Intracranial tumor in the pineal gland projection was detected in 73.3 % of cases, suprasellar localization – in 20 %. The ratio of synchronous and metachronous disease variants is heterogeneous and multidirectional and varies from 1,3:1 (according to large retrospective and prospective studies of Y. Zhang, X. Fang, T. Gui, S. Qureshi et al.) to 1:2,1–1:4 (according to meta-analysis of M.C. DeJong, R. Yamanaka et al.). All TRb cases were detected before the age of 60 months; the synchronous variant was detected before the age of 36 months in most clinical cases.

Morphological and molecular biological study of the tumor substrate in children with TRb is currently disjointed in relation to the intraocular and intracranial segments of this phenomenon, Rb and Pb respectively.

The most significant characteristics presented by determination of the germline RB1 gene mutation in blood samples, assessment of RB1, TFF1 proteins expression, a variant of the mutational event in the RB1 gene, the presence of N-MYC gene amplification, 1q gain, 16q loss in the tumor substrate of intraocular and/or pineal/suprasellar localization.

In the treatment of children with the TRb phenomenon, both complex protocols and individual therapy programs are used. The optimal therapeutic strategy is unknown.

Providing a better quality of life for the children with cancer after recovery proves to be one and important aspect of rehabilitation. Preserving the fertility of children, adolescents and young adults can improve the chances to lead a full, active life, and have biological children after oncological treatment. It is necessary to consider that the degree of reproductive potential impairment as well as recovery perspectives can be assessed solely after the gonadotoxic therapy completion. Whereas fertility preservation practice proves to be more effective before the oncological treatment. The complexity of discussing with young patients and their parents (custodian parents) the risk of decrease or loss of reproductive function, of fertility preservation methods, of necessity to agree to another possible invasive intervention raises quite a range of ethical and legal problems, which claim special attention on behalf of doctors and patients’ protection.

Hageman’s disease is a rare hereditary disorder of hemostasis, characterized by a deficiency of coagulation factor XII, accompanied by prolongation of blood clotting time (Lee–White) and activated partial thromboplastin time. These laboratory abnormalities are often thought to indicate an increased risk of bleeding, similar to hemophilia. This leads to the unnecessary use of transfusions and hemostatic therapy, since bleeding is rare in these patients. The article provides a review of the literature on Hageman’s disease and describes clinical cases of surgical treatment of children with factor XII deficiency.

Pheochromocytoma a tumor of the medullary layer of the adrenal gland composed of chromaffin cells that produces catecholamines (adrenaline, noradrenaline, and dopamine), is a special case of sympathetic paraganglioma.

Pheochromocytoma is a life-threatening catecholamine-secreting tumor of chromaffin cells, which requires early and timely diagnosis and treatment. he clinical manifestations of pheochromocytoma are arterial hypertension, headaches predominantly in the occipital region, palpitations, tachycardia and hyperhidrosis.

Anesthesiological support during surgeries for neoplasm removal (pheochromocytoma) is accompanied by life-threatening conditions in the perioperative period.

Purpose to the study – to present the peculiarities of perioperative period management in a patient with pheochromocytoma.

Materials and methods. A 17-year-old patient was diagnosed with pheochromocytoma of the right adrenal gland. After thorough preoperative preparation, surgical intervention in the volume of adrenalectomy was performed. Due to compliance with the modern strategy of anesthesiology adopted in our institution, the course of the postoperative period was stable. On the 3rd day after the operation the child was transferred to the specialized department, and on the 9th day he was discharged from the hospital under the dynamic observation of the endocrinologist at the place of residence. Event-free survival rate in the patient amounted to 82 weeks.

Conclusion. Thorough preoperative preparation of the patient with alpha1-adrenoblockers for 1 month, stabilization of hemodynamics in the perioperative period prevents life-threatening complications, such as hemodynamic disorders in the form of intraoperative hypertension and subsequent hypotension after clamping of tumor-feeding vessels, postoperative hypotension, within the framework of combined anesthesia using epidural analgesia.

Bloch–Sulzberger syndrome (SBS, incontinentia pigmenti) is a rare genodermatosis associated with pathogenic variants of the IKBKG (NEMO) gene localized on the long arm of the X chromosome (Xq28). Among the clinical manifestations, the most common are typical stageby-stage skin lesions, the development of ophthalmological and neurological pathology, as well as abnormalities of teeth, hair and nails. Cancer in SBS is extremely rare and known by sporadic cases of retinoblastoma, Wilms tumor, leukemia and skin cancer.

We performed clinical and genetic investigation of two families with SBS. In both cases, the deletion of the 4–10 exons of the IKBKG gene was transmitted through the maternal line. In the first case, ophthalmological changes were suspicious of retinoblastoma, but further examination revealed vitreous fibrosis and retinal detachment. In the second case, one of the three sisters was diagnosed with squamous cell skin carcinoma at the age of 11.

These clinical observations and the literature review, make necessary to increase the awareness of pediatric oncologists about SBS due to the possible association of this syndrome with an oncogenic risk.