Today, the contribution of hereditary tumor syndromes to the development of cancer in children is obvious, which determines the need for screening programs and selection of the most effective methods of anticancer therapy. One of the most aggressive hereditary tumor syndromes is heritable TP53-related cancer syndrome (hTP53rc, formerly known as Li–Fraumeni syndrome), characterized by a high risk, early onset and recurrent cases of malignant neoplasms in one patient. The article describes current data on hTP53rc syndrome and the features of its clinical course, and provides international recommendations for monitoring and cancer screening in pediatric patients with hTP53rc syndrome. As a clinical observation, we present an analysis of the registry of patients with relapsed and refractory forms of medulloblastoma (n = 241) with the assessment of its incidence in cases of germline mutations in the TP53 gene with the description of their medical history and the influence of this genetic event on the outcomes. The results of our study, as well as data from international literature, indicate unfavorable prognosis in tumors, including medulloblastoma, in patients with hTP53rc syndrome, however, such factors as early screening, surveillance and early and adequate therapy can help to increase their life expectancy. The study was approved by the Independent Ethics Committee and the Scientific Council of the Almazov National Medical Research Centre of Ministry of Healthcare of the Russian Federation.

Introduction. Central nervous system (CNS) tumors are the most common pediatric solid tumor, that need multimodality treatment approach including surgery, intensive chemotherapy (CT) and radiotherapy (RT). Due to toxicity, mostly late, RT has limited use in children, especially those under 3 years of age. The physical characteristics of proton beam therapy (PBT) minimize the risk and types of toxicity compared to photons, making it the preferred choice for pediatric use. Aim – to analyze the experience of PBT in patients under 18 years of age with various types of CNS malignancies, the assessment of risk factors for acute and late toxicity and its clinical manifestations. Materials and methods. A retrospective analysis of 63 courses of PBT performed in 58 patients with CNS malignancies for the period from 2018 to 2022 was carried out on Proton Center of the Sergey Beresin Medical Institute. The manifestations of local and systemic toxicity (predominantly acute) were analyzed, with an assessment of the influence of age, the volume of RT, the use of previous and concomitant CT on the severity of adverse events (AE). Results. In the study cohort, patients with embryonal CNS malignancies predominated (72.3 %). Median age was 5 years 2 months, median follow-up was 15 months. In 36 % of cases, a complete response was achieved by the start of PBT. Patients with craniospinal irradiation (CSI) prevailed (60 %). Among the manifestations of toxicity, AE grade I–II predominated. The most common AE were local reactions (dermatitis (84 %), focal alopecia (96 %)). Among systemic AE, hematological complications (84 %) were the most often occurred. A more pronounced toxicity profile was registered in the group with CSI, while concomitant CT, the patient’s age, previous CT did not significantly affect the severity of most of the assessed AE parameters (p > 0.05). The analysis of late toxic effects was difficult due to the short follow-up period, the cumulative effect of other treatment modalities on the AE’s development. The reported complications included persistent focal alopecia (14 % of cases), endocrinopathies (7 %), neurological manifestations (6 %). One (2 %) child had a severe neurological deficit, secondary epilepsy with psychomotor regression, which can also be associated with the potentiating effect of previous CT and high-dose CT. Conclusion. The analysis of our data and literature review allows to conclude that PBT has relatively low toxicity profile, which is the determining factor for choosing this method of RT in pediatric patients. The main risk factor of AE’s was CSI. The acceptable acute toxicity of repeat PBT makes it possible to be used in pts with disease progression or relapse in case of absence of alternative therapeutic options.

Comparative retrospective analysis of treatment results of three different chemotherapy protocols - ALL BFM 90m, ALL MB 91 and PECO 92 — in primary ALL patients aged before 18 years, registered in Moscow and St-Petersburg clinics from 01.01.1993 to 01.01.1999 is presented. It has been shown, that treatment results of PECO 92 protocol have appeared much worse, thus, any differences in treatment results for children with ALL between ALL BFM 90m and ALL MB 91 protocols were not revealed. Event-free survival (pEFS) of St-Petersburg' patients, received PECO 92 protocol (60±3%), was significantly worse, in comparison with patients treated according to ALL BFM 90m protocol (74±4%; р=0,0056) and ALL MB 91 protocol (73±4%; р=0,0239). The high incidence of relapses became a main cause of efficacy decreasing. Differences of induction and remission death incidences between three chemotherapy protocols were not revealed. Significant and most expressive EFS differences between PECO-92 and two other protocols were obtained in boys, in a 1—10 age group, and in patients with leukocytes count > 100 000/mm3, in patients with non-T-ALL and in patients with spleen size >4 cm.

Primitive myxoid mesenchymal tumor of infancy (PMMTI) is an aggressive tumor with a high rate of local recurrence, rare metastasis and poor response to chemotherapy.PMMTI is a rare soft-tissue sarcoma that preferentially affects infants. It is isolated from the group of infantile fibrosarcomas or myofibroblastic tumors. PMMTI differs from other tumors in the clinical course, morphological features and primarily molecular genetic changes. ETV6-NTRK3 gene fusion is characteristic of infantile fibrosarcomas. However, it is not detected in patients with PMMTI. BCOR ITD had been described in patients with PMMTI and it allowed to define this tumor from the group of infantile fibrosarcomas.Unified treatment approaches have not been identified for this tumor yet. Radical surgical removal is preferred treatment. BCOR ITD is a target. Nowadays search for targeted drugs is ongoing and it could help to solve the problem of PMMTI treatment.

Recent diagnostic and therapeutic advances in pediatric oncology have led to increased survival rates in children with malignancies. Today many investigations are devoted to the adverse effects during and after anticancer treatment, possible methods of their prevention and control. Menorrhagia is a serious complication in post-pubertal females who suffer from thrombocytopenia during myelosuppressive treatment. The issues of the effective prevention of this complication is highly discussed and a great interest is devoted to Gonadotropin-releasing hormone (GnRH) analogues. This option was not chosen by chance: the perspective method of prevention ovarian function is hormonal gonadoprotection. There are no definite data about the effectiveness of GnRH analogs yet, and it remains controversial. In this issue we’d like to summarize international data and our experience of the use of GnRH agonists in adolescents during chemotherapy.

Recent diagnostic and therapeutic advances in pediatric oncology have led to increased survival rates in children with malignancies. Today many investigations are devoted to the adverse effects during and after anticancer treatment, possible methods of their prevention and control. Menorrhagia is a serious complication in post-pubertal females who suffer from thrombocytopenia during myelosuppressive treatment. The issues of the effective prevention of this complication is highly discussed and a great interest is devoted to Gonadotropin-releasing hormone (GnRH) analogues. This option was not chosen by chance: the perspective method of prevention ovarian function is hormonal gonadoprotection. There are no definite data about the effectiveness of GnRH analogs yet, and it remains controversial. In this issue we’d like to summarize international data and our experience of the use of GnRH agonists in adolescents during chemotherapy.

Treatment results in children with acute lymphoblastic leukemia (ALL) treating in St.-Petersburg hospitals according to two modified version of German protocol CO ALL-92 from 01.01.1993 to 01.01.2007 are presented. 438 primary A LL patients aged from 4 months to 17 year s have been included in the study . ALL diagnosed according to international criteria. Based on prognostic factors patients were a llocated to one of two risk groups, which determined therapy intensity . The total treatment duration in both groups w as 2 years and consist ed of 5.5–8 months intensive phase with subsequent maintenance therapy . A comparative treatment results analysis in children with A LL according to two modified versions of COALL-92 is presented.

В статье представлены результаты лечения детей с острым лимфобластным лейкозом (ОЛЛ) в Санкт-Петербурге за период с 01.01.1993 по 01.01.2007. В качестве терапевтической программы использовались две модифицированные версии немецкой программы COALL-92: протоколы PECO-92 и COALL-С-Петербург-92, основанные на применении интенсивной химиотерапии. В исследование было включено 438 первичных пациентов с ОЛЛ в возрасте до 18 лет, проживающих в Санкт-Петербурге и Ленинградской области. Диагноз острого лимфобластного лейкоза устанавливали на основании международных критериев, с последующей стратификацией пациентов на 2 группы риска. Приводится сравнительный анализ результатов лечения в соответствии с двумя версиями немецкого протокола COALL 92. Обсуждаются причины различной терапевтической эффективности протоколов PECO-92 и COALL-С-Петербург-92 и пути дальнейшей оптимизации терапии ОЛЛ у детей.

Regardless the success gained in treatment of acute lymphoblastic leukaemia, several problems still remain to be solved, such as: overcoming primary drug resistance and minimizing the amount of relapses as well as decreasing of chemotherapy toxicity without detriment to the final outcome of the treatment. Development of an optimal chemotherapeutical strategy still remains a hot issue. Objective: to evaluate an efficacy of two modifications of German protocol COALL-92 in treatment of ALL in children in St.-Petersburg. Methods: the retrospective analysis of results of treatment in patients under 18 years old with ALL was performed. The diagnosis was confirmed according to international criteria. The treatment was performed via protocols PECO-92 and COALL-St.-Petersburg-92. Results: 438 initial patients with ALL were treated in St.-Petersburg clinics during the period from 01.01.1993 to 01.01.2007. At the time of analysis the probability of event-free survival (pEFS) was 60% in group of PECO-92 protocol and 70% — in COALL group (plog-rank = 0,048), probability of relapse-free survival (рRFS) was 65 and 74% (plog-rank = 0,002), probability of overall survival was (pOS) 78 and 70%, correspondingly (plog-rank = 0,079). Conclusion: inclusion of protocol treatment in practice of St.-Petersburg hospitals resulted in significant improvement of treatment results in children with ALL. The problem of both versions of COALL protocol is high rate of postremission mortality due to high toxicity of intensive stage if chemotherapy. Key words: children, acute lymphoblastic leukemia, intensive chemotherapy. (Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (3): 33–42)

Regardless the success gained in treatment of acute lymphoblastic leukaemia, several problems still remain to be solved, such as: overcoming primary drug resistance and minimizing the amount of relapses as well as decreasing of chemotherapy toxicity without detriment to the final outcome of the treatment. Development of an optimal chemotherapeutical strategy still remains a hot issue. Objective: to evaluate an efficacy of two modifications of German protocol COALL-92 in treatment of ALL in children in St.-Petersburg. Methods: the retrospective analysis of results of treatment in patients under 18 years old with ALL was performed. The diagnosis was confirmed according to international criteria. The treatment was performed via protocols PECO-92 and COALL-St.-Petersburg-92. Results: 438 initial patients with ALL were treated in St.-Petersburg clinics during the period from 01.01.1993 to 01.01.2007. At the time of analysis the probability of event-free survival (pEFS) was 60% in group of PECO-92 protocol and 70% — in COALL group (plog-rank = 0,048), probability of relapse-free survival (рRFS) was 65 and 74% (plog-rank = 0,002), probability of overall survival was (pOS) 78 and 70%, correspondingly (plog-rank = 0,079). Conclusion: inclusion of protocol treatment in practice of St.-Petersburg hospitals resulted in significant improvement of treatment results in children with ALL. The problem of both versions of COALL protocol is high rate of postremission mortality due to high toxicity of intensive stage if chemotherapy.Key words: children, acute lymphoblastic leukemia, intensive chemotherapy.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (3): 33–42)

The article demonstrates the treatment results on the protocol the treatment of children with acute lymphoblastic leukemia (ALL) (COALL-92–Saint-Petersburg) after 10 years of follow-up. Between January, 1999 and August, 2008, a total of 272 children and adolescents 0–18 yr of age, from Saint-Petersburg and its area were eligible for the protocol. All the patients have met diagnostic criteria for ALL. Those with a mature B-cell phenotype and FAB-L3 morphology were excluded. The diagnosis was based on morphological evaluation of the peripheral blood and bone marrow smears, immunophenotyping and cytogenetic analysis. All patients were classified as being at lower (LR, 47%) or higher (HR, 53%) risk of relapse. The intensive phase of treatment lasted 5, 5 months in low risk group and 8 months in high risk group and consisted of 4 parts (induction, consolidation, CNS-treatment and reinduction). It was followed by maintenance treatment until 2 years from date of diagnosis. After an observation time of 11 years, the estimate for EFS of all 272 evaluable patients was 67,7 ± 3,1%, the estimate of probability of RFS was 74,1 ± 3,3%, and probability of overall survival was 75,6 ± 3,0%. Key words: acute lymphoblastic leukemia, intensive chemotherapy, children. (Pediatric Pharmacology. – 2010; 7(6):50-56)

The article presents the results of the treatment of children with acute lymphoblast leukemia (all) according to the coall 92 program in St.-Petersburg from 01.01.1999 to 01.01.2005. 160 primary all patients, aged 4 months to 17 years 4 months were included in the study. International criteria were used to diagnose acute lymphoblast leukemia. A 2 years course of treatment in both risk groups included a 5,5–8 months phase of intensive chemotherapy followed by maintenance therapy. 6 years after the protocol introduction in the common group of patients the following survival rate indices were obtained: the 6 years uneventful survival rate was 63 ± 4,6%, the 6 years relapses free survival rate was 69 ± 4,7%, the 6 years general survival rate was 79 ± 3,7%.Key words: acute lymphoblast leukemia, children, intensive chemotherapy.