Relevance. Currently, the assessment of the level of minimal residual disease (MRD) is the standard in evaluating the effectiveness of therapy in acute lymphoblastic leukemia (ALL) in adults and children. Although, the necessity to study MRD at the induction therapy is not in doubt, the prognostic value of MRD in the period after induction is the subject for scientific discussion. Several studies suggest that MRD-positive status after induction chemotherapy associated with poor prognosis, and the reappearance of significant level MRD during follow-up allows impending relapse to be identified and to begin appropriate therapy in low leukemic cells level.

Aim – to determine the prognostic value of post-induction MRD on overall (OS), relapse-free (RFS), and event-free (EFS) survival in children with B-precursor ALL who received program treatment at the N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia.

Materials and methods. The study included 73 pediatric patients with initial B-precursor ALL. The median age of the patients was 5.2 years (from 1 to 16 years). The treatment was according to the ALL IC-BFM 2009 protocol. MRD detected on day 15 and 33 of induction therapy, and day 78 of consolidation beginning. MRD level was determined by flow cytometry method.

Results. EFS and RFS were the same for patients with MRD-positive status on 78 day of treatment 76.8 ± 12.3 % and 96.2 ± 2.6 % for MRDnegative (p = 0.06). Detailed assessment of MRD revealed a cohort of high-risk patients with MRD-negative status on 78 day of therapy with 100 % OS (observation time – 6 years).

Conclusion. In all risk groups, patients with negative MRD status showed a better survival result, which indicates the possibility of additional stratification by risk groups not only at the induction, but also during a consolidating treatment protocol.

Relevance. Chronic granulomatous disease (CGD) belongs to the group of primary immunodeficiencies. Patients with CGD have an impaired quality of life, severe infections and inflammatory organ damage. Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment method for CGD. The authors of the article presented the experience of HSCT in patients with CGD in the Russian Children’s Clinical Hospital.

Materials and methods. 20 (19 primary and 1 repeated) HSCT during the period from 2009 to 2020 were performed in nineteen patients with CGD. All patients had a long history of infections, three or more foci of chronic infection, 9 patients had a generalized BCG infection. Bone marrow (ВМ) from a related HLA-identical donor was the source of hematopoietic stem cells (HSC) for 4 (21 %) patients, peripheral blood stem cells (PBSC) for 2 (10.5 %). ВМ from a unrelated fully HLA-identical donor was performed in 9 (47.4 %) patients, PBSC – 2 (10.5 %). ВМ from a unrelated 9/10 HLA-compatible donor was performed in one (5.3 %) patient. In one case (5.3 %) the HSC source became PBSC from a unrelated 9/10 HLA-compatible donor after TcRαβ/CD19+ depletion. In 68.5 % (n = 13) cases the conditioning regimen included threosulfan, fludarabine, melphalan, and antithymocyte globulin. In 2 (10.5 %) patients, melphalan was excluded from the conditioning regimen; in 4 (21 %), it was replaced by thiotepa.

Results. The overall survival (OS) was 88.9 ± 10.5 %, the event-free survival (EFS) was 88.1 ± 7.9 %, and there was no transplant mortality. Transplant rejections were observed in two patients who received HSC from a unrelated 9/10 HLA-compatible donor with a previous conditioning regimen that included only one alkylating agent. In 4 patients (21 %) there was a prolonged persistence of mixed chimerism after HSCT without clinical and laboratory signs of CGD. After successful transplantation all patients were cured of the infectious and inflammatory diseases characteristic of CGD.

Conclusion. Results of HSCT in patients with CGD can be considered satisfactory, the OS and EFS are high. Failure of HSCT is associated with transplant rejection, which is most likely due to the donor and patient mismatch, as well as the use of conditioning modes with reduced intensity.

Relevance. Reliable and long-term venous access is one of the most important condition for a successful leukemia therapy in children. Safe and convenient access to a central vein allows to provide chemotherapy, adjuvant treatment, parenteral nutrition and blood transfusion. It decreases the likelihood of phlebitis development and reduction of the peripheral venous network in comparison with peripheral venous access. The use of totally implantable venous port systems reduces risks of severe complications associated with re-catheterization of the central vein thus it improves patient’s quality of life.

The purpose of the study is a retrospective assessment of the experience of use and analysis of the complications of totally implantable venous port systems in children with diseases of the blood system.

Materials and methods. The data of 61 patients of the pediatric hematology clinic with venous port systems have been analyzed.

Results. Perioperative complications developed in 3 (4.9 %) patients Median time of using of port systems was 679 catheter-days. Delayed complications requiring removal of the device developed in 8 (13.1 %) patients. Infectious complications were the reason for device removal in 3 (2.9 %) patients, mechanical complications in 5 (8.2 %) patients. No thrombotic complications were found.

Conclusions. The use of venous port systems in children with hematologic diseases for a long period of time is an effective and safe way for central venous access providing.

Relevance. Diagnostic algorithms are an effective tool for the early detection and proper monitoring of patients with a rare pathology.

The purpose of the study was to study the epidemiological, medical history, clinical and laboratory features of Gaucher disease (GD) in children in the Russian Federation (RF) to improve the algorithm for its diagnosis in a pediatric cohort of patients.

Materials and methods. A retrospective study of data on children with GD included in the pediatric registry of National Health Medical Research Center for Children of the Ministry of Health of Russia was conducted. The data recording period is from 2006 to 2016.

Results. The database contains 115 children with GD. The prevalence of the disease was 0.32 per 100 thousand children, with predominance in the Ural and North Caucasian federal districts. Only in 25 % of patients the diagnosis is confirmed within 6 months of the initial treatment. The family nature of the symptoms is established in 22 % of cases. Clinical polymorphism of GD leads to an erroneous interpretation of the diagnosis at primary reversibility in 85 % of cases; unjustified diagnostic and therapeutic measures, including surgical ones, in 70 % and 50 % of cases, respectively, thus leading to a delay in establishing the correct diagnosis up to 3.5 years and prescribing adequate treatment up to 4 years from the date of the examination. Key parameters for diagnosing GD include: damage to the parenchymal organs in the form of splenomegaly in 100 % and hepatomegaly in 94.8 % of patients; a change in hematological parameters in the form of anemia in 86.1 % and thrombocytopenia in 91.3 %; a change in biomarkers in the form of an increase in chitotriosidase activities in 94.0 % and aspartate aminotransferase in 51.0 %; ferritin concentration in 70.6 %, against a background of a decrease in iron content in 60.5 % and lipid metabolism (cholesterol in 54.0 % and high density lipoproteids in 85.0 %); elongation in the coagulogram of activated partial thromboplastin time in 66.2 % and prothrombotic time in 51.6 %; pathology of the skeletal system in the form of chronic bone pain and bone crises in 43 % and 18 % of patients, respectively; limb deformity of the type of “Erlenmeyer flasks” on the radiograph in 55.6 %; involvement of the central nervous system in patients with type II and type III hypertension in the form of oculomotor apraxia in 100 % of cases. An improved algorithm for diagnosing GD in children is proposed.

Conclusion. Optimization of the algorithm for diagnosing GD in pediatrics will improve the provision of medical care to children with this orphan pathology in the RF.

Relevance. Immune tolerance induction (ITI) is the only approach proven to eradicate inhibitors in hemophilia A patients. ITI with Octanate® (human VWF-stabilized FVIII) has been shown to be effective at eradicating inhibitors, even in poor-prognosis patients. Here we report interim data from two observational, prospective studies on the use of Octanate® for ITI in patients in Russia.

Purposes of research. The primary objective was to assess the efficacy of ITI. Secondary objectives included assessment of time to ITI success and inhibitor eradication.

Patients and methods. Patients of any age with any severity of hemophilia A and a FVIII inhibitor  0.6 BU/mL were eligible. The ITI regimen was at the discretion of the treating physician.

Results. The analysis included 73 patients. ITI outcomes were assessed in 63 patients who had completed the study, of whom 56 (89 %) had  1 poor prognostic factors. Inhibitor eradication was achieved by 77.1 % (37/48) of primary ITI patients and 71.4 % (45/63) of all patients, in a median of 2.4 months (range – 0.0–27.4) for both groups. Complete success was achieved by 72.9 % (35/48) of primary ITI patients in a median of 8.9 months (range – 2.4–28.0) and 66.7 % (42/63) of all patients in a median of 10.5 months (range – 2.4–28.0). No relapses were reported after complete or partial ITI success. Of the patients with  1 poor prognostic factors, 67.9 % achieved inhibitor eradication and 62.5 % complete success.

Conclusions. ITI with Octanate® in a real-world setting showed rapid and sustained success, even in patients with poor prognostic factors.

Inflammatory myofibroblastic tumor (IMT) is a rare type of neoplasm with undetermined biological potential. IMT can occur in both childhood and adulthood. The standard of therapy is radical surgical treatment, but for patients with inoperable/recurrent or metastatic forms of IMT, therapeutic options are very limited. This literature review describes specific clinical, morphological and biological characteristics of this neoplasm, provides modern approaches to the diagnosis and treatment of IMT.

Autologous hematopoietic stem cell transplantation (auto-HSCT) is a standard for the treatment of oncological, hematologic, and also some immune diseases, ensuring the restoration of blood counts after high-dose chemotherapy. In children, the success of mobilization and collection of hematopoietic stem cells (HSCs) is especially important. Mobilization schemes for children are decided on an individual basis, which requires the development and implementation of recommendations for improving the efficiency of mobilization and collection of HSCs. Mobilization schemes include the use of granulocyte colony-stimulating factor in the form of monotherapy or in combination with CXCR4 antagonists. These schemes are ineffective in some children, which requires re-mobilization or rejection of transplantation, which negatively affects the prognosis. When preparing a patient for HSCs collection, it is necessary to take into account all previous therapy, the patient’s age, weight and height indicators, and general somatic state. Harvesting the required amount of HSCs will allow for high-dose therapy followed by auto-HSCT, and thereby increase the effectiveness of treatment. It is necessary to optimize the protocol for mobilization of HSCs with a large bias for pediatric patients, which will clearly define the criteria for mobilization, give indications for this procedure and determine the criteria for technical collection, which will allow to obtain the optimal number of CD34+ cells, which will ensure the success of the treatment.

Red cell pyruvate kinase deficiency is the most common glycolytic defect causing congenital nonspherocytic hemolytic anemia. Pyruvate kinase is the enzyme involved in the last step of glycolysis – the transfer of a phosphate group from phosphoenolpyruvate producing the enolate of pyruvate and ATP (50 % of total energy ATP of erythrocytes). ATP deficiency directly shortened red cell lifespan. Affected red blood cells are destroyed in the splenic capillaries, leading to the development of chronic hemolytic anemia. It is an autosomal recessive disease, caused by homozygous and compound heterozygous mutations in the PKLR gene. There are no exact data on the incidence of pyruvate kinase deficiency, but the estimated frequency varies from 3: 1,000,000 to 1:20,000. The clinical features of the disease and the severity are highly variable. Diagnosis of pyruvate kinase deficiency is based on the determination of pyruvate kinase activity and molecular genetic study of the PKLR gene. The variety of clinical manifestations, possible complications, as well as the inaccessibility of diagnostic methods complicate the diagnosis.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for different spectrum of diseases. This type of treatment is constantly improving, but HSCT remains a risky procedure with various possible complications, the main is – chronic “graft versus host” disease (cGVHD). сGVHD is immune disregulation, and characterized by a variety of clinical manifestations that reflect the multiple underlying pathophysiology mechanisms. The study of cGVHD has now made great progress, but there’s still a lot of questions. General characteristics, risk-factors of development, clinical manifestations, pathogenesis of cGVHD will be discussed in this article. Clinical case presented in this article explains usage of basic and novel agents for cGVHD treatment, prevention criterions for treatment of cGVHD in children.

This article describes the experience of using the Pulsavac Plus debridement system for atraumatic treatment of the skin in one of the forms of graft versus host diseases after allogeneic hematopoietic stem cell transplantation.

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.

Bilateral nephroblastoma is rare and is about 5 % of the total number of patients. The modern strategy of treatment children with bilateral Wilms tumor requires a comprehensive approach. An important task is to preserve as much of the renal parenchyma as possible, which will be sufficient for normal kidney function and development of the child. However, in subtotal kidney damage organ-preserving treatment is not always possible. In this case, the only curative option is bilateral nephrectomy followed by continuous renal replacement therapy. To date, the literature describes isolated cases of adjuvant chemotherapy in children on peritoneal dialysis. The article presents a clinical case of specific therapy with topotecan for a child after bilateral nephrectomy, a carrier of peritoneal dialysis catheter on the background of progression of the underlying disease.

High-dose chemotherapy (HDCT) with autologous hemopoietic stem cell transplantation (auto-HSCT) is currently an integral part of a standard of care for younger medulloblastoma (MB) patients and MB patients with relapse. As HDCT regimens are characterized by neurotoxicity, it may add to the one of radiation therapy. Therefore, some patients may develop post-irradiation clinical symptoms and MRI changes characteristic for disease progression, pseudoprogression. We report on a case of a 16-year old patient with relapsed MB treated by standard chemotherapy with consequent HDCT and craniospinal irradiation with a boost to cranial fossa posterior. One month after the radiation therapy was finished she developed focal neurological symptoms. The MRI and PET scan have shown cerebellar changes characteristic for disease progression. However, the therаpy with corticosteroids and bevacizumab was able to resolve most clinical symptoms. The MRI scan have also shown evident positive dynamics. Therefore, the clinical course and imaging dynamics corresponded to pseudoprogression. The probability of pseudoprogression may be higher in patients with MB relapse receiving second irradiation and HDCT with auto-HSCT. As we often do not have a morphological proof of relapse, we have to distinguish between progressive disease and pseudoprogression by a complex of clinical course and imaging data.

Relevance. Development and application of novel treatment methods for patients with retinoblastoma (Rb) is a great task since it may provide higher rates of eye salvage and reduce adverse effects of current therapy.

Aim of the study was to represent the history of Rb eye-sparing treatment in Russia and worldwide through the one clinical case.

Materials and methods. A child was treated by systemic chemotherapy, plaque brachytherapy using non-described techniques, cryotherapy and external beam radiotherapy. Intravitreal chemotherapy was approached for treatment of vitreous seeding. Vitreoretinal surgery with melphalan irrigation was successfully performed after failure of vitreous hemorrhage conservative treatment and parents’ refusal to indicated enucleation. The child died from CNS disseminated esthesioneuroblastoma.

Results. The use of various treatment modalities helped to save the single eye.

Conclusions. Intravitreal chemotherapy was introduced in Russia for the first time. Performed vitreoretinal surgery with melphalan irrigation was proved to be a safe and effective technique in case of vitreous hemorrhage in the eye with Rb. External beam therapy is associated with fatal second tumors development.