Introduction. Down syndrome (DS) is one of the most common chromosomal abnormalities. Children with DS have an increased risk of developing acute lymphoblastic leukemia (ALL). Standard therapy is usually used to treat ALL in children with Down syndrome, but the outcome is worse than in the general population. The high toxicity of therapy is a particular problem.

The purpose of the study – in this study we presents a comparative analysis of the results of therapy for children with DS and ALL (DS-ALL) who received therapy according to the ALL-MB 2008 and ALL-MB 2015 protocols.

Materials and methods. The analysis included primary ALL patients, aged 1 to 18 years, who received therapy in Russian and Belarusian clinics participating in the Moscow–Berlin study from January 2008 to December 2020. To analyze the treatment results of DS-ALL patients, a “comparison group” was formed from all patients with ALL registered in the database, using the matched-pair method. Survival was calculated using the Kaplan–Meier method, toxicity analysis and clinical-genetic parameters were investigated using nonparametric statistical methods.

Results. The results of therapy both among patients with DS-ALL who received therapy according to ALL-MB 2008 and ALL-MB 2015 in comparison with “sporadic” ALL (non-DS-ALL) are unsatisfactory. The event-free survival rate of patients with DS-ALL in the ALL-MB 2008 group was 61 ± 7 % versus 85 ± 4 % among non-DS-ALL (p = 0.001), in the ALL-MB 2015 group – 67 ± 7 % versus 84 ± 4 % respectively. Overall survival in the ALL-MB 2008 group was 70 ± 7 % in children with DS versus 88 ± 4 % in non-DS (p < 0.001), in the ALL-MB 2015 group – 78 ± 6 % versus 92 ± 3 % respectively (p < 0.001). The risk of therapy-related death was higher in patients with DS: 20.6 ± 6.1 % versus 4.6 ± 2.2 %; p < 0.001 in the ALL-MB 2008 group and 18 ± 4.1 % versus 3.3 ± 1.3 %; p < 0.001 in the ALL-MB 2015 group, without a significant increase in the risk of relapse. The effectiveness of induction therapy among patients with DS treated according to ALL-MB 2008 versus children with DS-ALL treated according to ALL-MB 2015 was 80 % versus 92 % respectively (p = 0.018). The probability of achieving continuous complete remission was also lower in the ALL-MB 2008 group compared to ALL-MB 2015 – 57 % versus 75 %; p < 0.001 respectively. Thus, the results of treatment of DS-ALL according to the ALL-MB 2015 protocol were better than those according to the ALL-MB 2008.

Conclusion. The results of therapy for patients with DS-ALL are still unsatisfactory today, this circumstance dictates the need for new approaches to optimize therapy. The main problem for these patients remains the high toxicity of therapy and the associated lethality. Further progress in the treatment of DS-ALL may be associated with the development of new approaches to concomitant therapy, the use of molecular-targeted drugs and immunotherapy, as well as with the study of the molecular genetic characteristics of this subgroup of patients.

Background. Recovery of children with acute lymphoblastic leukemia (ALL) was one of the most significant achievements of clinical oncohematology of XX century. Success in the treatment of ALL became possible due to comprehensive (clinical, morphoimmunological, cytogenetic) diagnostics and the development of differentiated, risk-adapted treatment protocols. The German group BFM (Berlin–Frankfurt–Munster) became a pioneer in creating effective treatment programs for children with ALL. Its new principles and approaches in treatment allow the vast majority of patients to be cured.

The aim of the study – presentation of the treatment results of children with ALL based on the ALL IC-BFM 2002 protocol as part of a multicenter long standing study.

Materials and methods. There were 592 patients with a newly diagnosed ALL in the study . The average age of patients was 10.5 years (from 4 months to 21 years). Treatment was carried out according to the ALL IC-BFM 2002 protocol in 11 clinics from 01.11.2003 to 16.05.2022. The overall (OS), relapse-free (RFS) and event-free (EFS) survivals of patients were estimated on 01.07.2022.

Results. Complete clinical and hematological remission was achieved by the 33 day of therapy in 582 (98.3 %) cases. 10-year OS was 90.4 ± 1.5 %, RFS – 83.9 ± 1.9 % EFS – 82.4 ± 1.9 %. The analysis of survival of ALL patients in prognostic risk groups showed that 10-year OS in the standard risk group was 92.8 ± 1.7 %, RFS – 86 ± 2.2 % and EFS – 84.3 ± 2.2 %. Among the patients of the intermediate risk group the OS, RFS and EFS were 94.6 ± 2.6 %, 82.2 ± 5 % and 81.7 ± 5 %, respectively. The prognosis of ALL patients from the high-risk group turned out to be the least favorable: OS was 69.5 ± 8.7 %, RFS – 62 ± 9.4 % and EFS – 60.3 ± 9.3 %.

Conclusion. Based on the results of a multicenter study the ALL IC-BFM 2002 protocol showed high efficiency with the possibility of achieving a 10-year OS of 90.4 ± 1.5 %. This protocol turned out to be reproducible both in federal and regional clinics with high rates of long-term patients survival. This fact allows including it in the clinical recommendations of the Ministry of Health of Russia.

Background. There are increasing data of targeted therapy efficacy of different types of Langerhans cell histiocytosis (LCH) with inhibitors of BRAF-specific serin-threonine kinase (BRAF-inhibitors) in cases with BRAF V600E mutation published last years. At the same time there are no published data of use of inhibitors of MAPK/ERK pathway (MEK-inhibitors) in pediatric patients with BRAF-negative forms of LCH.

Purpose of the study is to evaluate efficacy and safety of MEK-inhibitor (cobimetinib) in eight pediatric BRAF V600E-negative refractory LCH patients.

Materials and methods. The study included 8 children with various forms of LCH. All patients received therapy according to the LCH-IV protocol and were diagnosed with progression of LCH during or after termination of the treatment. The response to the therapy was assessed in accordance with the international scale Response Evaluation Criteria in Solid Tumors (RECIST v.1.1). The assessment of the toxicity was performed in accordance with the international scale of Common Terminology Criteria for Adverse Events (CTCAE v.5.0).

Results. Complete response was not achieved in any patient. Partial response was established in 5 cases. One patient was diagnosed with disease progression in three months after termination of the therapy. The incidence of adverse events was high.

Conclusion. Cobimetinib therapy is effective in BRAF V600E-negative refractory pediatric LCH patients. The response to the treatment can be delayed. All cases of the toxicity were dose depended and successfully resolved after dose correction. Further research is needed to define duration of treatment and optimal dosage.

Introduction. Cryotherapy (CT) is one of the main methods of small retinoblastoma (Rb) treatment and remains the “gold standard” for the treatment of small tumors of pre-equatorial localization, however, the number of studies in the literature on this problem is small, and they are represented only by single studies.

Purpose of the study – to evaluate long-term results of CT of Rb.

Materials and methods. During the period from 2008 to 2021 CT was performed in 87 children (98 eyes, 169 tumors) with Rb. 49 (56 %) patients were boys, 38 (44 %) were girls. The average age at the time of treatment was 22 months (from 0 to 73 months). Bilateral RB was observed in 70 (80 %) patients, unilateral – in 17 (20 %). In 19 (22 %) cases, CT was performed on a single eye. A total of 169 tumors were treated by CT. Most of the treated tumors (138 foci, 82 %) had pre-equatorial localization (35 tumors – on the mid periphery and 103 tumors – on the far periphery of the fundus). 31 (18 %) tumors located postequatorially. The mean tumor thickness was 1.2 (from 0.4 to 2.9) mm, the mean basal diameter was 2.2 (from 0.9 to 4.9) mm.

In the vast majority of cases (n = 78, 87 %), CT was performed with an incision of the conjunctiva and separation of the tenon capsule in the projection of the tumor, then a double application with an exposure of 60 seconds was carried out according to the “classic” technology (“freeze–thaw”). In 13 % of cases (n = 9), CT was performed transconjunctivally without a conjunctival incision. In all cases, carbon dioxide (–78 ºC) was used as a refrigerant.

Results. Complete tumor regression after CT was achieved in 63 % of cases (106 tumors), of which in 91 % of cases (96 tumors) – after one CT session, in 8 % (9 tumors) – after 2 sessions, in one (1 %) case– after 4 CT sessions. In 10 % of cases (17 tumors) an incomplete regression was observed and subsequent transpupillary laser thermotherapy was performed. In 27 % of cases (43 tumors), continued tumor growth or recurrence of the tumor was detected, and therefore other methods of local treatment were used (brachytherapy, laser thermotherapy, intra-arterial and intravitreal chemotherapy). As a result of organ-preserving treatment, 90 (92 %) eyes were preserved, 8 (8 %) eyes were enucleated.

Complications after CT included vitreous hemorrhage in 3 (3 %) patients, preretinal hemorrhage in 7 (8 %) cases, subretinal hemorrhage in 2 %, local retinal detachment in 2 %, one (1 %) case of retinal tear, and vitreoretinal traction in 2 (2 %) patients. The mean follow-up time after CT was 44 months (from 4 to 121 months).

Conclusion. CT still takes an important place in Rb local treatment, especially in the treatment of small tumors of peripheral localization. However, long-term results have shown that one session of CT is often not enough to achieve complete tumor regression and it requires either repeated use of CT or application of other local methods, mostly transpupillary laser thermotherapy. However, the use of CT is especially relevant in the treatment of small tumors of pre-equatorial localization, which are resistant to thermotherapy, especially in cases of a tumor height more than 1 mm and basal diameter more than 2 mm, which are too large and inconvenient for thermotherapy of peripheral Rb.

In recent years, we have seen a revolution in the treatment of patients with hemophilia A. The emergence of new methods of non-factor and the development of gene therapy raise a natural question for doctors: what are the prospects for the classical treatment of hemophilia A using factor concentrates? This is especially true for patients with hemophilia A and inhibitors (HAI), for whom, until now, the only option to reduce the frequency of hemorrhagic manifestations has been the use of bypassing agents that do not allow complete control of bleeding. Improving the results of treatment of patients with HAI was possible only with complete eradication of inhibitors. The most effective and safe method to get rid of inhibitors is immune tolerance induction therapy (ITI). With the advent of emicizumab and the truly fantastic results of its use in patients with HAI, doctors are increasingly faced with the question of the need for ITI. This issue is especially acute in children with HAI.

This review provides basic information about modern advances in the treatment of hemophilia A, and also determines the place of substitution therapy drugs in the present and future.

Thanks to the treatments that are happening today, the survival rate of patients with retinoblastoma (Rb) has reached 100 %. Despite the positive results of Rb treatment, intraocular complications are observed in observations. Complications that cause visualization of the fundus impede the control of tumor tissue in dynamics, which is associated with enucleation of the eyeball. Despite modern advances in the use of intraocular surgery, a positive and important aspect is the fact that any experience of intraocular infections with a high risk of growth dissemination, which requires an accurate assessment of the state of growth in dynamics and confidence in the stability of remission, which is not always possible with opaque optical environments. In this regard, the question arises of conservative methods of treatment of persistent complications.

Given the small age of patients, this makes it difficult to perform conservative treatment in full. Effective are retrobulbar injections, which deliver the drug as close as possible to the posterior pole of the eye. However, for the maximum concentration of the drug, frequent injections are necessary, which is quite traumatic, accompanied by pain, and their frequent implementation contributes to scarring of the retrobulbar tissue. One way to avoid these adverse events is retrobulbar infusion therapy.

As a result of retrobulbar infusion therapy, a silicone tube (catheter) is placed in the retrobulbar space for several days, followed by the administration of drugs several times a day.

The review contains data on intraocular complications after local treatment of Rb, as well as possible methods for their relief.

Introduction. Venous thrombosis is a rare condition in children, but now there is a significant increase in cases among hospitalized children. Thrombosis in children is a multifactorial disorder, there are various risk factors, both inherited and acquired, such as a central venous catheter.

The aim of the study is to evaluate the incidence of thrombophilia among patients aged 0 to 18 years after a history of deep vein thrombosis (DVT).

Materials and methods. We have retrospectively analyzed the medical records of young patients (0–18 years) of from 2017 to 2021 of the Outpatient Consultative Unit of Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology and selected patients with objectively confirmed DVT, who were examined to exclude thrombophilia. Patients who did not have a full range of laboratory tests were not accounted for in the study. The patients who had DVT during infancy had additional tests at the age older than one year.

All patients were divided into 2 groups: with and without thrombophilia. Chi-square test was used to assess the statistical significance of differences between groups.

Results. We found 149 children with DVT: 103 patients were completely investigated for thrombophilia and a follow-up investigation is required for another 46 patients. Among 103 patients we didn’t confirm any prothrombotic condition in 54 of them, and thrombophilia was present in 49 patients. The prevalence of thrombophilia was estimated among children with DVT (n = 103): protein C deficiency – 3 %, antithrombin III deficiency – 4 %, protein S deficiency – 4 %, antiphospholipid syndrome – 1 %, mutation FV Leiden (hetero) – 7 %, FII G20210A (hetero) – 8 %, combined – 8 %, others – 13 % (increased concentration of fVIII, increased concentration of lipoprotein (a), high level of homocysteine).

While comparing groups of patients with and without thrombophilia by age and sex, and by various clinical characteristics (localization of thrombus, underline clinical condition and some others) no statistically significant differences were revealed.

Conclusion. Thrombophilias contribute to the occurrence of thrombosis in children. Results of thrombophilia screening rarely influence acute treatment decisions, so it is important to understand the limitations of this approach. Nevertheless, in some cases it is important to try to identify children with a tendency to develop thrombosis, since these patients may be candidates for prophylactic anticoagulation in situations of high risk of developing venous thromboembolism.

Radiation necrosis of the brain (BRN) is the most frequent and dangerous iatrogenic complication of radiation therapy of tumors and non-tumor diseases of the brain and the base of the skull. The risk of its development increases with an increase in the amount of radiation, single and total doses and due to synergy with the action of adjuvant chemotherapy used. The pathogenesis of BRN is based on damage to the microcirculatory bed in the tumor and surrounding tissues with the development of edema and impaired trophic neuroglia with its necrosis, which in most cases are irreversible. After treatment of brain tumors, differential diagnosis of BRN is carried out with the resumption of tumor growth or its pseudoprogression and requires the use of a set of imaging methods. Treatment of BRN in separate patients may consist of surgical removal of the necrotic area, but in most patients it is possible to carry out only drug therapy with corticosteroid and anti-VEGF drugs that allow to slow down the development of BRN, improve the quality of life and prolong its.

Background. Acquired factor VIII (FVIII) deficiency or acquired hemophilia A (AHA) is very uncommon in children. Patients with AHA usually present with abnormal or unexpected bleeding which may be life-threatening. These patients usually have unexplained, prolonged, and isolated activated partial thromboplastin time (aPTT). Consequently, FVIII activity should be immediately evaluated. Bleeding prevention is important in patients with AHA.

Case report. We present a case of a previously healthy 13-year-old female who presented with intramuscular hematoma, soft tissue hemorrhage, and epistaxis who was eventually diagnosed with AHA.

Conclusion. To our knowledge, the present report is one of the few reported cases of an Asian patient that was diagnosed with acquired hemophilia A at a young age.

A peripherally inserted central catheter (PICC) line allows permanent vascular access and is widely used in pediatric oncology. In patients, who fully completed antitumor treatment, the PICC line should be removed. In some cases, however, the procedure may be complicated and such a catheter is then called a ‘hard-to-remove’ or a ‘non-removable’. This article describes a clinical case of successful non-surgical removal of a PICC line with a developed fibrin sheath.

According to the available data, children are less susceptible for developing a severe course of COVID-19 and commonly have mild or asymptomatic course of infection. It is reported about an increased risk of having more severe course in infants, at the same time, according to the literature data, the course in children receiving antineoplastic and immunosuppressive therapy is milder in comparison with other concomitant pathologies. This article presents the unique clinical case and the literature review of combined COVID-19-pneumonia and extremely rare congenital myeloid leukemia in the infant with the description of long-term infection persistence, changes in clinical data in dynamics, bone marrow test results and the experience of using donor plasma with antibodies to SARS-CoV-2.

The wide antibiotics use in different areas of medicine has significantly increased the incidence of pseudomembranous colitis caused by Clostridium difficile. Strong necessity of antibacterial therapy in hematological patients is the reason of a higher frequency of this complication after programmed chemotherapy and hematopoietic stem cell transplantation. The atypical course of clostridial colitis makes it difficult to diagnose, leads to delay of treatment and fatal complications. We presented the case of clostridial colitis with atypical clinical manifestations in the 8-year-old child with Hodgkin’s lymphoma. Disease was complicated by colon perforation and fecal peritonitis, which required surgery and long-term rehabilitation. The analysis of publications devoted to clostridial colitis in patients with hematological malignancies was carried out and possible reasons of its atypical course was reviewed. The ways to improve the diagnosis, treatment and prevention of this serious complication are presented.

Neuroblastoma (NB) is the most common extracranial tumor in children aged 0–14 years. Modern approaches to the treatment are based on the stratification of patients into 3 risk groups. Despite the use of multimodal therapy, the prognosis for high-risk patients remains unfavorable. Tumor cells in NB in most cases express the glycolipid disialoganglioside GD2, which is considered as a target for immunotherapy. Naxitamab, a humanized anti-GD2 antibody of the IgG1 class, is one of the modern drugs widely used for immunotherapy throughout the world. Naxitamab has shown higher affinity to GD2 in vitro.

On September 9, 2022 Advisory Board was held in Moscow with the participation of experts from leading Russian federal and regional centers of oncology and an invited international expert Jaume Mora – Head of the Children’s Oncology Center of the Sant Joan de D u Children’s Hospital in Barcelona. The purpose of Advisory Board was to discuss approaches to the treatment of patients with refractory/recurrent high-risk NB in Europe and the Russian Federation and the place of immunotherapy in this treatment. Leading federal centers presented the experience of using Naxitamab due to the Expanded Access. The experts of Advisory Board made recommendations on further steps and prospects for the use of immunotherapy and chemoimmunotherapy in Russia.