Background. One of the possible options to intensify therapy in patients with high-risk malignant tumors is high-dose chemotherapy (HDCT) with autologous hematopoetic stem cell rescue. However, this method has a high risk of acute and delayed toxicity, and, sometimes doesn’t meet the expected effectiveness. This confirms the necessity of more considerate approach for choosing the category of patients for this therapeutic option with the determination of the most significant factors on the part of the patient and the type of malignant tumor.Objective. Analysis of the results of HDCT with autologous hematopoetic stem cell transplantation (HSCT) in children with high-risk solid malignancies, conducted in the Department of pediatric oncohematology and BMT of the Federal State Budgetary Institution “V.A. Almazov National Medical Research Center”.Design and methods. We perform a retrospective analysis of 55 cycles of HDCT with autologous hematopoetic stem cell rescue provided from 2017 to 2020 in 39 patients with high-risk malignant tumors. The toxicity and efficacy of the method were assessed taking into account the frequency of infectious complications, early post-transplant mortality, event-free (EFS) and overall survival (OS).Results. The predominant category of patients were children with CNS tumors (61.5 %). Mean age of the patients was 2 years 9 months. At the time of HDCT 35.9% of patients were in complete remission (CR), 64.1 % had signs of active disease (AD). In 59% of patients, one course of HDCT was performed, in 41 % — tandem transplantation was performed according to the recommendations of the protocol for the treatment of the disease. The most common conditioning regimen was carboplatin + etoposide (27.3 %). The predominant source of hematopoietic stem cells were peripheral stem cells (87.3 %). The frequency of infectious complications in the post-transplant period was 100 %, neutropenic enterocolitis (61.8 %) and febrile neutropenia (34.5 %) were predominant. A high frequency of reactivation of CMV infection (25.4 %) was noted, meanwhile CMV disease occurred in 35.7 % of cases. The most important prognostic factor was the disease status at the time of HDCT. 2-year OS incidence of 85.7 % vs 65.3% and EFS 85.7 % vs 39 % in patients with CR and AD respectively. After completing the course of HDCT with autologous HSCT 94.8 % of patients continued anticancer therapy.Conclusion. HDCT with autologous HSCT demonstrates a satisfactory toxicity profile and can improve OS and EFS in children with high-risk malignant tumors. A reliable prognostic factor that determines the effectiveness of the method is the disease status at the time of HDCT.

Neuroblastoma (NB) is the most common extra-cranial solid tumor in infants with the most heterogeneous clinical course to compare with other malignant diseases. Due to intensive multimodal anticancer treatment there are an increased number of survivors and issues related to long-term effects are becoming increasingly important. One of them is the risk of secondary malignant neoplasms. This article represents a clinical case of T-cell lymphoblastic leukemia in a child aged 2 years and 5 months who received combined antitumor therapy for NB with an intermediate risk group under the age of one year. We observed literature data to investigate the incidence of second malignant neoplasms in patients with NB for the period from 1948 to 2018 and analyzed risk factors.

Introduction. Methotrexate (MTX) is one of the most commonly used anti-tumor preparations which confirm it effectiveness against the large spectrum of the oncological diseases in children. Today the use of high doses of the MTX (g/m2 ) in the monotherapy or in combination with other chemotherapeutic agent is a standard of treatment of such nosology as osteosarcoma, tumors of the central nervous system (CNS), lymphomas, acute lymphoblastic leukemia. Despite of the developed recommendations on the fluid therapy, therapeutic monitoring, use of leukovorin which allowed to reduce the expected toxicity among some patients it is not always possible to prevent the development of complications. Ex post evaluation of different doses of schedule of the high-dose MTX is necessary in order to formulate new and effective treatment strategies with respect to the individual specifics of the patients. Materials and methods . During the period from October 2015 to February 2018, a patient cohort (n = 26) who received high-dose MTX therapy with the following nosology: osteosarcoma – 4, hemoblastosis – 11, and CNS – 11 tumors was evaluated. The average age of the patients was 7.3 years old; ratio of boys:girls – 2.25: 1. The used doses were ranged from 1 to 12 g/m 2 , the doses schedules ranged from 4 to 36 hours; the total number of courses during the observation period was 94; the average number of courses per patient was 3. In all cases, the level of MTX in the blood serum was monitored with correction of the dose of leucovorin according to international recommendations. Estimated toxicity parameters were the following: allergic reactions, skin and mucous membrane damage, neurologic disorders, myelosuppression, hepatic transaminase and creatinine growth. Results. Transitory toxicity was noted for 100 % of patients, of which clinically significant was in 62.7 % of cases. The development of complications that had required the use of antibacterial and blood transfusion therapy occurred after 36 courses of therapy (38.2 %), of wich in 24 cases (66.6 %) MTX was performed in combination with other antitumor agents. No cases of acute kidney injury were presented, there was no significant difference in creatinine level before and after high-dose MTX courses. The highest frequency of episodes of hepatotoxicity was noted in the group of patients diagnosed with “osteosarcoma”. After reduction the episodes of toxicity with the use of high-dose MTX, all patients continued programmed chemotherapy. Conclusions. Against the background of an adequate accompanying therapy (infusion therapy with alkalization of urine, pharmacodynamic monitoring, correction of the leucovorin dose), it is possible to achieve satisfactory tolerability of high doses of MTX. The combination of high doses of MTX with other antitumor drugs leads to a significant increase in the toxicity. Despite of the noted complications of therapy, continuation of treatment with the use of previous doses of MTX (does not require reduction) is possible, and a decrease in the rate of MTX removal is not always a predictor of episodes of the toxicity.

In the present work, the immunoadjuvant properties of the influenza ANSI vaccine virus after intranasal administration in combination with recombinant GBS polypeptides was tested in mice. According to our data, co-administration of recombinant GBS polypeptides and influenza ANSI vaccine resulted in the increase in the immunogenicity and protective efficacy of bacterial proteins. Combined vaccination with the GBS polypeptides and influenza ANSI vaccine has a potential to be used not only for prophylaxis infections caused by SGB, but also for prevention of the bacterial complications of influenza.

Intragastric administration of the acetaminophen in rats (the dose is 750 mg/kg of body weight for 5 days) induces essential ultrastructural changes in theirjejunum which reflectis impaired sucking, secretion, protective-barrier functions and probably dysbacteriosis

The changes of the hepatocytes ultrastructure in patients with chronic hepatitis C were studied. The analysis of the findings showed that the signs of continuous hepatic pathologic process preserved in patients with chronic hepatitis C and complete response to interferon treatment. The changes of the hepatocyte ultrastructure in chronic hepatitis C might be used as predictors of the outcome of hepatitis natural course and for evaluating the efficacy of the therapy.