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Follicular lymphoma is one of the most common non-Hodgkin’s lymphomas in adults. One of the rather rare variants of follicular lymphoma is pediatric follicular lymphoma. This variant, despite the name, is diagnosed not only in children, but also among young adults. Pediatric follicular lymphoma is characterized by early (I, II) stages, the absence or weak BCL2 expression, and the predominant absence of t(14;18)(q32;q21) translocation. Treatment tactics vary widely from radical surgical tumor resection with subsequent follow-up to chemoimmunotherapy with rituximab.This article presents a clinical case of advanced pediatric follicular lymphoma (stage III) in a 5-year-old patient. Using a combined treatment approach (surgery followed by immunochemotherapy) allowed to achieve a complete metabolic response which lasts more than a year.

Background. Renal failure (RF) is unfavorable prognostic factor for the multiple myeloma (MM) patients, negatively affecting overall survival. High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is associated with an increased risk of HSCT-related complications and mortality, which may limit its implementation in MM patients with RF, especially in patients with severe RF requiring hemodialysis.Aim. To analyze the effectiveness and adverse events of high-dose chemotherapy followed by auto-HSCT in newly diagnosed MM patients with severe RF requiring hemodialysis.Materials and methods. We analyzed the data of 7 newly diagnosed MM patients with severe RF requiring hemodialysis, who received auto-HSCT.Results. Complete remission achieved 2 (28.6 %) patients, very good partial remission – 4 (57.1 %) patients, partial remission – 1 (14.3 %) patient on the 100th day after auto-HSCT. Complete renal response achieved 6 (85.7 %) patients, 1 (14.3 %) patient remained a minimal renal response. Auto-HSCT led to an improvement in both hematological and renal responses in 1 (14.3 %) patient, hematological response – in 2 (28.6 %) patients. With a median follow-up of 19 months, median progression-free survival and overall survival were 43 and 81 months, respectively. In the early post-transplant period, febrile neutropenia (71.4 %) and grade III–IV mucositis (71.4 %) were most often diagnosed. In the study group of patients, there was no auto-HSCT-related mortality.Conclusion. Auto-HSCT is an effective and safe method of treating newly diagnosed MM patients with severe RF requiring hemodialysis.

Plasmoblastic lymphoma is a rare, aggressive B-cell malignancy with poor long-term survival. Plasmoblastic lymphoma occurs most commonly in patients infected with human immunodeficiency virus (HIV), but cases associated with solid organ transplantation have also been reported, less commonly plasmoblastic lymphoma registers in immunocompetent patients. The disease is more common in male patients (75 %) aged from 8 to 62 years (median age 50 years), and most often the tumor lesions are localized in the oral cavity. Rare localizations of plasmoblastic lymphoma include pleura, testicles, mammary glands, lungs, and skin. As casuistic areas of lesions, the central nervous system can be noted.The article describes a clinical case of HIV-positive pediatric patient with rare plasmoblastic lymphoma of chiasmosellar zone. The disease was complicated with secondary hypocorticism and hypotyreosis, a deficiency of somatotrophic hormone and diabetes insipidus.

In preparing the review, articles on the functioning of the reverse transcriptase enzyme of endogenous repeat sequences LINE1, the mechanisms of action and antitumor activity of viral reverse transcriptase inhibitors. Articles available in the biomedical literature information databases SciVerse Scopus, PubMed, Web of Science, Russian Science CitationIndex (RSCI) were analyzed. The review used information from 140 publications, of which 95 and 39 were published, respectively, over the last ten and three years, 2 articles present the results of clinical studies, and 45 articles refer to results demonstrating the anticancer properties of the studied compounds in various models in vitro and in vivo. Aim. Based on data on the functional properties of the reverse transcriptase enzyme of endogenous repeat sequences LINE1 (long interspersed nuclear elements 1), analyze the potential use of viral reverse transcriptase inhibitors in oncology, presenting their classification and main mechanisms of action. About 98 % of the human genome consists of repetitive sequences, most of which are represented by mobil genetic elements, the activation of which leads to increased genome instability. These include long (LINE) and short (SINE) interspersed nuclear element repeated DNA sequences interspersed nuclear elements, respectively, which occupy about 45 % of the human genome. Increased expression levels of these sequences in the genome have been identified in many forms of malignant neoplasms. Their transposition occurs due to the expression of LINE1-encoded reverse transcriptase, whichis homologous to viral reverse transcriptase. To date, reverse transcriptase inhibitors of viruses of nucleoside and non-nucleoside structure have been developed and are successfully used in the clinic. These drugs demonstrate an inhibitory effect on both LINE1 reverse transcriptase and telomerase, which provides the tumor cell with the ability to overcome replicative senescence. Due to these properties, these compounds are expected to exhibit both their own antitumor activity and increase the sensitivity of tumor cells to the therapy of malignant neoplasms, which is experimentally confirmed in models of malignant tumors in vitro and in vivo. Use of reverse transcriptase inhibitors in combination therapy seems advisable both to prevent further genome rearrangements caused by LINE1 and to suppress the survival of tumor cells by inhibiting telomerase activity.

Background. A significant advancement in the treatment of high-grade aggressive non-Hodgkin’s lymphomas and acute lymphoblastic leukemia is the inclusion of high-dose (1000–5000 mg/m2) methotrexate in the treatment protocol. This approach has significantly increased the long-term survival rate, but it has been associated with toxicity, requiring supportive care. Factors that predict toxicity were identified, including genes involved in the metabolism (MTHFR) or transport (SLCO1B1) of methotrexate. The analysis of methotrexate metabolism has identified additional genes responsible for the elimination of this drug, allowing for more effective prevention and treatment of methotrexate-associated toxicity.Aim. To study the genetic polymorphisms of enzymes involved in the methotrexate metabolism and associated toxicity in the treatment of pediatric acute lymphoblastic leukemia and non-Hodgkin’s lymphomas.Materials and methods. Data were analyzed in specialized medical databases such as Pubmed, Scopus, Web of Science, Frontiers, and Google Scholar from 2001 to 2024.Results. The main predictors of high-dose methotrexate-associated toxicity are gene polymorphisms in MTHFR, SLCO1B1, ARID5B.Conclusion. Despite the contradictory data presented in the literature, it is important to consider the detection of polymorphisms during high-dose methotrexate treatment in order to administer timely supportive care and prevent significant toxicity.

L-asparaginase is one of the most effective drugs in pediatric and adult acute lymphoblastic leukemia treatment. But drug side effects are an important problem. pancreatitis and pancreatic necrosis are not common (2–18 %) complication, but high chance of severe disease with fatal outcome make to bring in careful attention of pediatric oncologists-hematologists, surgeons, intensivists, radiologists. Recognizing multidisciplinary importance of this problem, at June 21st, 2023 at Morozov Children’s Clinical hospital a Round table on pancreatitis/pancreatic necrosis after L-asparaginase use was organized. This article presents expert recommendations from federal and regional clinics in diagnosis and treatment of such severe complication.

The use of high-effective, multicomponent, risk-adopted chemoimmunotherapy schemes in children with Burkitt lymphoma reached advanced long-term progression-free survival over 90 % even for high risk patients. Unfortunately, conventional therapeutic strategy for relapsed/refractory disease is not accepted, and the effectiveness of carboplat‑in- and gemcitabine-containing regimens is unsatisfactory. Clinical experience of rituximab, ibrutinib and nivolumab in combination with polychemotherapy and own clinical case of successful relapsed Burkitt lymphoma treatment with targeted therapy and following autologous and allogeneic hematopoietic stem cell transplantation are presented. Proposed program could achieve a complete remission of Burkitt lymphoma, but short-term after allogeneic hematopoietic stem cell transplantation diagnosed T-cell precursor acute lymphoblastic leukemia became fatal for the patient.

Treatment intensification of acute lymphoblastic leukemia in children with L-asparaginase (L-ASP) improves therapy effectiveness and shows high survival rates. The unique biological properties of this enzyme make it possible to suppress tumor blasts proliferation by reducing blood asparagine concentration. L-ASP use is limited by toxicity and hypersensitivity reactions observed in 75 % of cases. Although most complications during L-ASP therapy are mild/moderate and are manageable with adequate accompanying therapy, the development of severe side effects leads to forced withdrawal of L-ASP, which significantly reduces the likelihood of a favorable outcome in children with acute lymphoblastic leukemia. One of the most severe toxicity manifestations is the development of asparaginase-associated pancreatitis. It worsens the prognosis and may cause patients’ death. This article presents both current data about asparaginase-associated pancreatitis and treatment experience of this complication at the Research Institute of Pediatric Oncology and Hematology of the N. N. Blokhin National Research Center of Oncology.

Background. There is a mounting evidence in the scientific literature that susceptibility to SARS-CoV-2 infection could vary. The severity of COVID-19 symptoms can range from asymptomatic to severe respiratory failure, requiring prolonged artificial ventilation. The underlying causes of this range of clinical manifestations remain unclear. Identification of the risk factors that may cause this variation in clinical symptoms is important for identifying the most susceptible populations at highest risk. This should help improve prevention measures, reduce hospitalizations, and decrease the mortality rate of the disease. Previously, an association has been found between the severity of COVID-19 and the genetic markers rs11385942 G>GA and rs657152 A>C.The aim. To assess the impact of carrying polymorphic markers rs11385942 G>GA and rs657152 A>C on the severity of COVID-19 in patients undergoing specific therapy. Materials and methods. A total of 240 patients hospitalized with a coronavirus infection were included in the study. All patients received therapy with favipiravir or remdesivir. The presence of the rs11385942 G>GA and rs657152 A>C variants was determined in all patients. The study compared the length of hospital stays, frequency of patient transfers to the intensive care unit (ICU), and frequency of clinical outcomes (recovery or death) among carriers of allelic variants of the markers under investigation.Results. There were no significant associations between the carriage of variants rs11385942 G>GA and rs657152 A>C and the duration of patients’ hospitalization, frequency of patient transfers to the ICU, and patient outcomes.Conclusion. The carriage of rs11385942 G>GA and rs657152 A>C variants did not affect the severity or type of clinical outcomes in patients with COVID-19.

Multiple myeloma is a malignant tumor characterized by the proliferation of clonal plasma cells and currently remains an incurable disease, despite advances in therapy. Resistance and development of double refractoriness represent a significant problem, worsening the prognosis. To overcome double refractoriness, new proteasome inhibitors carfilzomib and ixazomib, the 3rd generation immunomodulator pomalidomide and monoclonal antibodies daratumumab, elotuzumab and isatuximab are used. Based on randomized phase III ICARIA-MM and IKEMA studies results, which demonstrated, along with a manageable safety profile, advantages in increasing the antitumor response depth, the rate of achieving negative minimal residual disease status and survival in all subgroups of patients with refractory/relapsed multiple myeloma, isatuximab is used in IsaPd (isatuximab, pomalidomide, dexamethasone) and IsaKd (isatuximab, carfilzomib, dexamethasone) combination. This article discusses the clinical pharmacology of isatuximab. The results of studies demonstrating the effectiveness and safety of antitumor therapy regimens including isatuximab, which made it possible to use it in clinical practice, are presented. We present a case report of a patient with refractory/relapsed multiple myeloma who received 3 lines of antitumor treatment, including class 2 proteasome inhibitors, lenalidomide and the monoclonal antibody elotuzumab. After 3 cycles of IsaPd (8 injections of isatuximab), partial remission and pain relief were recorded. The achieved antitumor effect, along with the absence of significant adverse events, facilitated the continuation of therapy at recommended doses.

Lymphoblastic lymphomas (LBL) are the second most common subtype of non-Hodgkin’s lymphomas in children and adolescents, accounting for 25–35 % of all non-Hodgkin’s lymphomas cases. The majority of all lymphoblastic lymphomas (80–85 %) are T-lymphoblastic origin; 15–20 % origins from B-cell precursors, biphenotypic LBL are extremely rare. Currently, the overall and relapse-free survival of children and adolescents with LBL exceeds 80 %, uses of modern therapy programs. However, the survival rates of patients with recurrent or refractory LBL remain low – 10 %. Optimization of therapeutic approaches in LBL follows the path of clarifying clinical, morpho-immunological and molecular biological risk groups, modification of treatment programs using new drugs (including immunotherapy, inhibitors of multifunctional intracellular signaling pathways (NOTCH, PI3K/AKТ/mTOR, JAK/STAT and MAPK), affecting the cell cycle regulation), and also a reduction in immediate and long-term toxicity. This article presents modern approaches to the diagnosis of LBL, staging and choosing of a treatment method.

Despite the therapy advances, largely due to the study of molecular biology, multiple myeloma remains an incurable disease, and refractory course or relapses significantly worsen the prognosis. In this regard, the development of effective therapeutic agents with fundamentally new mechanisms of action that provide increased survival is currently an urgent task. One potential immunotherapeutic target is signaling lymphocyte activation molecules (SLAMs), and the anti-SLAMF7 monoclonal antibody elotuzumab is used in combination with either lenalidomide and dexamethasone (Elo-Rd regimen) after 1 prior line of therapy, or with pomalidomide and dexamethasone (Elo-Pd regimen) after 2 or more lines of therapy. The results of studies demonstrated a survival benefit in all subgroups of patients with refractory or relapsed multiple myeloma when using elotuzumab. A manageable safety profile and a low frequency of grade III–IV induced myelosuppression were noted, which allows the use of elotuzumab in combination with lenalidomide or pomalidomide and dexamethasone in elderly and debilitated patients. We present our own experience of using elotuzumab in the treatment of patients with refractory/recurrent multiple myeloma. A clinical case of a patient in whom treatment with elotuzumab was initiated at an early stage (after 1 line of previous therapy) is presented; the effectiveness and safety of using the monoclonal antibody are assessed. A significant improvement in the patient’s clinical condition and positive dynamics according to laboratory data were noted already during the 1st cycle of Elo-Rd regimen with a further progressive deepening of the antitumor response along with satisfactory tolerability and the absence of significant adverse events.

The high efficacy of the currently used combined chemoradiotherapy for Hodgkin’s lymphoma not only significantly increased overall survival, but also made it possible for most patients to achieve the same quality of life as in a healthy population. at the same time, the problem of identifying late treatment complications, in particular cardiovascular the high efficacy of the currently used combined chemoradiotherapy for Hodgkin’s lymphoma not only significantly increased overall survival, but also made it possible for most patients to achieve the same quality of life as in a healthy population. at the same time, the problem of identifying late treatment complications, in particular cardiovascular diseases, remains an urgent problem, the timely diagnosis of which is an important task. the development of a second malignant neoplasm and the appointment of drug antitumor therapy with cardiotoxic agents necessitate a multidisciplinary approach. In the presented clinical observation, such tactics of patient management made it possible not only to timely identify late cardiovascular complications of Hodgkin’s lymphoma chemoradiotherapy, but also to conduct treatment for the second malignant disease with cardiotoxic agents with a positive antitumor effect.

Currently no therapy of acute lymphoblastic leukemia is conceivable without L-asparaginase drugs, with its antileukemic effect by extracellular asparagine depletion, thus preventing its admission to leukemic cell. Besides high antitumor effect, L-asparaginase drugs have side and toxic effects, such as hypersensitivity reactions, thrombosis, pancreatitis / pancreatic necrosis, and hepatotoxicity. For L-asparaginase safety profile improvement a technology of pegylation was lay down and PEG-aspargase drug produced. This drug has less toxic effects and recommended as first-line therapy of acute lymphoblastic leukemia. Drug monitoring for assessment the effectiveness and toxicity of L-asparaginase is optimal. Such therapy individualization helps for L-asparaginase dose finding and decrease frequency and severity of side effects.

Ffollicular lymphoma (FL) is one of the most common non-Hodgkin’s lymphomas in adults, while it is a diagnosis of exclusion in adolescents and children. Clinical manifestations of FL in children are represented by long-term asymptomatic lymphadenopathy, less commonly by extranodal areas involvement. treatment standards for FL in children have not been developed and may vary from observational tactics (with the radical resection of a single focus during a biopsy) to the use of radiation therapy and polychemotherapy. Pediatric type follicular lymphoma was first identified as a distinct variant in 2008 in the world Health organization classification of hematopoietic and lymphoid tissue tumors. Clinical, morphological (cytological type 3A), Immunohistochemical (absence of bcl2 expression in the center of the follicle) and cytogenetic (absence of t(14;18)(q32;q21)) features served as the reason for separation into an independent nosological variant. Despite the term “pediatric”, cases of pediatric type FL have been described in adults over 30 years of age. Most often, the disease is diagnosed in the early stages (I, II) and is characterized by a favorable prognosis. In children and adolescents, FL occurs not only of the pediatric type. we present a clinical case of a typical “adult” type FL (grade 1–2) in a 17-year-old patient. the cHop therapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone) with rituximab resulted in a complete remission, which lasted more than 2.5 years.

Background. Despite the modern therapy programs including hematopoietic stem cell transplantation, the treatment outcomes for children with acute myeloid leukemia (AML) remain unsatisfactory. The 5‑year overall survival rate is about 70 %. The 5‑year overall survival rate for patients with relapsed and refractory AML is 2 times lower (about 35 %). The treatment failure rate in primary AML and unsatisfactory results in relapsed and refractory AML make it necessary to optimize therapy protocols.Aim was a long-term retro- and prospective analysis of clinical and laboratory characteristics and treatment outcomes in patients with relapsed and refractory forms of AML.Materials and methods. This article presents the treatment results of 54 patients from 1 to 18 years of age, with relapsed and refractory AML treated at the N. N . Blokhin National Medical Research Center of Oncology from 1997 to 2022.Results. A comparison of 5 different programs revealed that patients who received second remission induction with the FLA + FLA scheme had 81.8 % of response (complete or partial) achievement. Analysis of the results in achievement the second remission in patients received epigenetic agents (azacytidine, decitabine, valproic and all-trans retinoid acids) with second-line chemotherapy found that treatment response rate was 100 % (n = 27), in contrast to patients received only second-line chemotherapy (n = 27) – 81.5 % (p = 0.003). The best treatment results were in group of patients whose treatment included epigenetic agents and allogenic hematopoietic stem cell transplantation after second remission induction – 5‑year overall survival was 51.3 ± 9.7 %.Conclusion. Intensive polychemotherapy with fludarabine- and cytarabine-containing regiments with following allogeneic hematopoietic stem cell transplantation and epigenetic agents are current trend and pathogenetically based approach for relapsed and refractory pediatric AML. Probable, the definition of the role and place of targeted drugs (gemtuzumab ozogamicin) could continue the advances in treatment of such unfavorable patient group.

Immunotherapy is a promising method in the treatment of cancer. PD-1 (programmed cell death protein 1) receptor and its ligand, which contribute to the reactivation of T-cells exerting their cytotoxic function against the tumor, are one of the targets of antitumor drugs. The effectiveness of immune checkpoint inhibitors has been demonstrated in the treatment of melanoma and non-small cell lung cancer. The spectrum of side effects of antitumor immune drugs differs from the classical ones observed in the cytostatics treatment. Immune-mediated adverse events can affect multiple organs, including skin, gastrointestinal tract, endocrine and nervous systems, and lungs. Pneumonitis is a potentially life-threatening complication and often requires immediate administration of corticosteroids.This article presents the case of a patient with relapsed Burkitt lymphoma treated with nivolumab and R-ICE (rituximab, ifosfamide etoposide, carboplatin) scheme. The therapy was effective, but complicated by immune-mediated pneumonitis. Corticosteroids administration resolved this complication and anti-cancer treatment was completed. The following nivolumab administrations were free of side effects.

The use of colony-stimulating factors became an autonomous approach in complex supportive care of blood tumors. By indications of granulocyte colony-stimulating factor (G-CSF) it is possible to reduce of neutropenic period, perform an optimal timing of therapy, decrease a number of infection complications. The development and active use of a new G-CSF drug formulation – pegfilgrastim do not decrease the duration of neutropenic period significantly, but reduced the frequency of drug administration, period of hospitalization and a probability of “ineffective” hematopoietic stem cell mobilization.In the current issue it is presented the results of modern studies, which demonstrate advantages of PEG-G-CSF in contrast to G-CSF, algorithm for febrile neutropenia risk assessment, the questions for G-CSF administrations in patients with blood tumors.

Background. Acute tumor lysis syndrome (ATLS) complicates the treatment of highly aggressive leukemias and lymphomas in children and leads to death in 21.4 % of severe cases. ATLS is based on the death of tumor cells, so the volume of decay products exceeds the excretory capacity of the kidneys. The ATLS risk group includes patients with acute lymphoblastic leukemia accompanied by hyperleukocytosis (above 100 × 109/L) and non-Hodgkin’s lymphomas with a large tumor mass (stage III–Iv of the disease). The development of acute renal and then multiple organ failure require intensive monitoring of ATLS clinical and biochemical markers and the development of optimal patient management tactics jointly by an intensive care physician and a pediatric oncologist-hematologist.Aim. To summarize the literature and our own clinical experience in the diagnosis and treatment of ATLS in pediatric oncohematology.Materials and methods. The literature data on the diagnosis and treatment of ATLS in children with oncohematological diseases were analyzed. Summarized own clinical experience from January 2009 to January 2022.Results. Of 379 patients with acute lymphoblastic leukemia and non-Hodgkin’s lymphomas, who are at risk for developing ATLS, 350 (93.4 %) patients underwent conservative ATLS therapy, of which in 31 (8.8 %) cases, hemodiafiltration was required to eliminate tumor decay products. The average number of hemodiafiltration procedures is 3 (from 1 to 15). Nevertheless, despite the whole range of therapeutic measures, the addition of infectious and multiple organ complications caused death in 7 (22.6 %) of 31 patients. Most (5 out of 7) fatal cases occurred between 2009 and 2013, and the number of lethal cases because of ATLS from 2014 to 2022 years were only 2. In 24 (77.4 %) patients, the signs of ATLS were successfully managed, the patients continued antitumor treatment. when observing patients for 6 years (from 7 months to 13 years), there were no signs of disease relapse, as well as renal dysfunction.Conclusion. prevention and treatment of ATLS, including cytoreductive prephase, infusion therapy, allopurinol and rasburicase, and in case of ineffectiveness, hemodiafiltration is the basis of modern intensive therapy for hematological malignancies in children. Additional study of the pathogenetic mechanisms of ATLS development, identification of key targets of drug therapy, and a multidisciplinary approach in the treatment of an extremely unfavorable group of oncohematological patients with advanced stages of the tumor process are possible components for further increasing the effectiveness of ATLS therapy.

Chronic myeloid leukemia is a ph-positive myeloproliferative disease, which is usually manifested by hyperleukocytosis and massive splenomegaly. Chronic myeloid leukemia is rare in childhood and adolescence, it accounts for 2 to 3 % of all leukemias cases. priapism is a rare manifestation of chronic myeloid leukemia and is an urgent urological condition that requires timely treatment to prevent long-term complications, in particular, erectile dysfunction.This review presents the literature information about priapism as the first sign of chronic myeloid leukemia, as well as the first description in the Russian literature of a clinical case of priapism in a 9-year-old patient with chronic myeloid leukemia.

Primary immunodeficiencies (PID) are genetically determined irreversible disorders of structure and/or functions of the immune system's cellular and humoral components, accompanied by frequent infectious diseases and contributing to the development of malignant neoplasms. Lymphomas are the most frequent oncological disease in PID patients: non-Hodgkin's lymphomas occur in 60 % of malignant neoplasms cases, Hodgkin lymphoma - in 20 %, leukemias - in 10 %, solid tumors - in 10 %. The risk of malignant lymphoproliferative diseases in PID patients amounts to 4-25 %, with the overall incidence of cancer 100-200 times higher than in immunocompetent population. Results of malignant neoplasms treatment in children with PID remain unsatisfactory due to the high rate of relapsed, refractory disease and anticancer therapy complications.This paper presents a clinical case of Hodgkin lymphoma with atypical localization in a female PID patient. peculiarities of this case are eye socket soft tissue involvement, slow response to therapy, and a high rate of infectious complications.

Background. Treatment results of acute lymphoblastic leukemia in children on protocol, developed by one of the leading research study group BFM (Berlin-Frankfurt-Munster) are impressive - longstanding overall survival rate comprise 93.4 %. The basis of success is a differential approach based on prognostic factors. In some local issues BFM protocols receive criticism because of high toxicity, but trying to find results of complex protocol toxicity assessment by modern scales in local literature, it was absent.Aim. To study a toxicity of acute lymphoblastic leukemia treatment by ALL IC-BFM 2002 protocol.Materials and methods. 119 patients with primary diagnosed acute lymphoblastic leukemia were enrolled the study. All the patients were treated by ALL IC-BFM 2002 protocol. Toxicity assessment was performed by the scale of National Cancer Institute (NCI) USA, 2nd version.Results. The most often variants of toxicity during treatment according to the ALL IC-BFM 2002 protocol were myelo-suppression, infections and hepatotoxicity of I-IV degrees of severity. Clinically significant toxicity (grade IV) was myelosuppression and necessity for transfusions in 76.8-100 % (depending on prognostic risk group and as such protocol arm). Nephro- and hepatotoxicity described on high-dosed methotrexate (2000 mg/m2 or 5000 mg/m2) were I-II grade in 89.5 % patients. Stomatitis grade I-II was in 93.7 % patients of standard and intermediate risk groups, but in the most (90 %) patients from high risk group it was higher - grade III-IV. Mortality on protocol ALL IC-BFM 2002 caused by infection complications was 1.6 %. It should be noted, that supportive care, prescribed in ALL IC-BFM 2002 protocol help to prevent and correct severe toxicity effectively.Conclusion. The toxicity profile of ALL IC-BFM 2002 protocol, analyzed by frequency of toxicity grade III-IV with whole supportive care approaches, is acceptable. The noted variants of toxicity were fully resolved without irreversible consequences for the patients.

Acute leukemia (AL) in children up 1 year old is very rare disease, comprise less 5 % of all pediatric AL cases. The clinical course of infant AL is extremely aggressive with frequent extramedullar dissemination, initial hyperleukocytosis and MLL aberrations. Predominance of unfavorable clinical and laboratory features leads to unsatisfactory treatment results by modern curative protocols in children up to 1 year old: 4-year event-free survival for acute lymphoblastic leukemia is 50.9 ± 4.5 % and 3-year event-free survival for acute myeloid leukemia – 72–74 %.Optimization of therapeutic programs for infant AL with consideration to anatomy and physiologic features of infants, inclusion of targeted drugs (blinatumomab), epigenetic and cell technologies is actual and not resolved problem in modern pediatric oncology-hematology.

Background. Anaplastic large cell lymphoma (ALCL) is a rare variant of highly aggressive lymphomas in children and adolescents. ALCL is characterized by a heterogeneous clinical manifestation with nodal and extranodal lesions, various morphological variants, variable expression of T-cell markers and cytogenetic aberrations involving the ALK gene. Due to the rarity of this disease (up to 10–15 % of all non-Hodgkin’s lymphomas in children), there are no uniform standards for ALCL therapy. Block treatment schemes similar to those applied in the treatment of B-cell non-Hodgkin’s lymphomas are used; less often there can be used protocols similar to the therapy of acute lymphoblastic leukemia. Taking into account the unfavorable effect on the prognosis of T-cell markers expression in ALCL, we developed protocol ALCL-NII DOG-2003, which considered the immunological features of the tumor.Aim. To assess the effectiveness of differentiated immunobased ALCL therapy by domestic protocol ALCL-NII DOG-2003.Materials and methods. From 01.03.1997 to 01.10.2022, 60 patients with primary diagnosed ALCL were included in the study. The diagnosis was based on histological, immunohistochemical and cytogenetic criteria of WHO classification of hematopoietic and lymphoid tissues tumors. According to treatment program, patients were subdivided in 2 groups: patients treated by NHL-BFM 95 protocol (n = 21) and by ALCL-NII DOG-2003 (n = 39). The male:female ratio was 1,3:1 in group of patients with NHL-BFM 95 protocol and 1,4:1 – in ALCL-NII DOG 2003. The effectiveness assessment was based on overall, event-free and relapse-free survival with SPSS 21.0 computed program. The differences between groups were significant with p ≤0.05.Results. The use of risk-adopted, immuno-oriented protocol made it possible to obtain a 10‑year EFS in 97.4 ± 2.6 %, whereas results of the standard NHL-BFM 95 protocol are 63.9 ± 10 % (p = 0.001).Conclusion. The use of a differentiated approach to ALCL treatment, considering not only the stage and prognostic risk group, but also the immunological features of the tumor, is more effective, and allows achieving significantly higher survival rates, than standard program (NHL-BFM 95).

Histiocytic cell tumors present as a difficult group of diseases in terms of differential diagnosis due to their rare frequency, heterogeneous clinical manifestations and ambiguous clinical course. Considering MAPK-signaling pathway mutations role (including BRAFV600E) in the pathogenesis of histiocytic cell tumors the importance of genetic studies in the diagnosis and choice of therapeutic strategy in these diseases increases. In the current issue modern classifications of histiocytic cell tumors, morphological and immunophenotypic features of histiocytic and dendritic cells, and the role of recurrent somatic mutations of the MAPK signaling pathway in the pathological histiocytic proliferation are presented. Particular attention is given to Langerhans cell histiocytosis, Erdheim–Chester disease and juvenile xanthogranuloma. Clinical and diagnostic characteristics of these diseases and therapeutic approaches are presented.

Histiocytic tumors are a highly heterogeneous group of diseases, with Langerhans cell histiocytosis occupying the main place among it. Despite the rare frequency of occurrence, long-term analysis of clinical, morpho-immunological and molecular-biological features has allowed the development of effective treatment protocols (especially in the pediatric cohort of patients). In addition to Langerhans cell histiocytosis, the histiocytic tumors group includes rare and casuistic variants, which include histiocytic sarcoma, Langerhans cell sarcoma, indeterminate dendritic cell tumor, interdigitating dendritic cell sarcoma, follicular dendritic cell sarcoma, and fibroblastic reticular cell tumor. The incidence of certain nosological variants is several cases per hundreds of millions of the population. Not surprisingly, the diagnostic criteria for this group of tumors need to be clarified, as do the therapeutic approaches. This review presents current data on rare histiocytic tumors, clinical features as well as morphological and immunobiological characteristics of the tumor substrate. The results of modern surgical and therapeutic treatment approaches are presented.

АКТУАЛЬНОСТЬ: Синдром острого лизиса опухоли (СОЛО) осложняет лечение высокоагрессивных лейкозов, лимфом у детей и сопровождается летальным исходом у 21,4 % больных. В основе СОЛО лежит распад опухолевых клеток, при котором объем продуктов распада превышает экскреторные возможности почек. В группу риска СОЛО входят пациенты с острым лимфобластным лейкозом, сопровождающимся гиперлейкоцитозом (выше 100×109/л) и неходжкинскими лимфомами с большой опухолевой массой (III–IV стадии заболевания). К настоящему времени объем тематических публикаций в агрегаторе медицинской базы данных PubMed не столь велик: за последние 10 лет насчитывает 12 статей, что делает задачу систематизации ранее накопленной и полученной в последнее время информации для практикующего врача еще более актуальной. ЦЕЛЬ ИССЛЕДОВАНИЯ: Обобщение современной научной базы по диагностике и лечению СОЛО у детей. МАТЕРИАЛЫ И МЕТОДЫ: Для освещения современной научной базы, касающейся диагностики и лечения СОЛО у детей с онкогематологическими заболеваниями, был проведен поиск в системах PubMed, ResearchGate, Web of Science Core Collection и Google Scholar за период с 2000 г. по август 2022 г. РЕЗУЛЬТАТЫ: В целом было обнаружено 94 статьи, из них 1 систематический обзор с метаанализом и 16 обзорных статей, соответствующих предъявляемым требованиям. ВЫВОДЫ: Консервативная профилактика СОЛО (инфузионная терапия, применение аллопуринола и расбуриказы, начало противоопухолевого лечения с циторедуктивной префазы) оказывается эффективной у 93,4–93,6 % больных. Однако, по некоторым данным, у 8,8–21,4 % пациентов СОЛО приобретает стремительный характер, сопровождаясь отсутствием возможности консервативно корригировать показатели калия, фосфора, мочевой кислоты. Дополнительное изучение патогенетических механизмов осложнения, определение ключевых мишеней лекарственной терапии и мультидисциплинарный подход в лечении крайне прогностически неблагоприятной группы онкогематологических больных с распространенными стадиями опухолевого процесса — возможные составляющие дальнейшего повышения эффективности терапии СОЛО.

Background. Actually, treatment results of Hodgkin lymphoma (HL) are the most dramatic oncohematology achievements, therefore modern treatment protocols designed to toxicity reduction with the same high level of patients’ survival. Time of complete response occupies a central position in the prognostic factors for HL and helps to find a group of patients whose treatment could be de-escalated.Objective: to evaluate the efficacy of original domestic risk-adopted protocol RDC POG-HL 2003 with treatment de-escalation and refused radiation therapy (RT) for early-responded patients.Materials and methods. 192 patients were enrolled in prospective RDC POG-HL 2003 protocol from February 2003 to November 2020. Median age was 12.8 years (from 3 to 17). Local stages (IA–IIA) were diagnosed in 48 (25 %) patients, disseminated (IIB–IVB) – in 144 (75 %) cases. For local (IA–IIA) stages by RCD POG-HL 2003 treatment included DBVE + RT, for disseminated (IIB–IVB) – BEACOPP escalated (esc.) + RT. In case of 70 % and more tumor reduction after 4 induction courses of BEACOPP-esc., the following treatment included less intensive schemes (ABVD, COPP/ABV). Because of high risk of breast cancer in girls after mediastinal RT, it was possible to omit a RT in case of early response.Results. All patients with local stages are alive by the time of study end. Event- and relapse-free survivals in this group were 97.8 ± 2.5 % (median follow up 181.9 ± 4.8 months). Event-free survival for disseminated stages patients was 90.3 ± 3.3 % (median follow up 179.1 ± 4.2 months), relapse-free survival – 93.5 ± 2.1 % (median follow up 191.7 ± 2.3 months) and overall survival – 97.9 ± 1.2 % (median follow up 196.3 ± 2.6 months). In 48 (25 %) patients it was possible to omit RT without reducing survival rates.Conclusion. Differentiated HL treatment with respect to disease stage and time of complete response is a key to success of treatment. Such approach permits us to reduce cumulative therapy toxicity by its de-escalation and, in some cases, to omit RT.

Nowadays due to modern risk-adapted treatment protocols high survival rates have been achieved in patients with aggressive B-cell lymphomas, even at stages III–IV these indicators overrun 90 %. Mainly these successes were associated with the inclusion of rituximab in the standard chemotherapy regimens. As the follow up period of the patients is lengthened, it has become clear that ongoing treatment is associated with the development of immediate and long-term adverse effects of chemoimmunotherapy. In Russia and the world, there are multicenter studies aimed at studying prognostic factors that make it possible to reduce single and/or total doses of chemotherapy drugs, and therefore, to reduce chemotherapy toxicity. The obtained data allow considering the early complete antitumor effect (after 2 courses of therapy) as an advantage factor, so it is possible to reduce program chemoimmunotherapy intensity without reducing high patients survival rates.

Background. Hemoblastoses treatment success in children made it possible to cure the vast majority of patients. The follow-up period exceeds tens of years, during which the problem of second tumors (ST) becomes urgent. The objective of the study was to characterize ST in patients who underwent a malignant tumor of hematopoietic and lymphoid tissues at the age of 0 to 18 years.Materials and methods. The study included 64 patients with ST development in the period from 1 to 38 years.Results. Most frequently ST developed after treatment of Hodgkin's lymphoma (45.3 %) and acute lymphoblastic leukemia (35.9 %), supported by high cumulative doses of alkylating agents and radiation therapy. Among STs, in 35.9 % of cases, thyroid cancer was diagnosed, in 10.9 % - acute leukemia, in 9.4 % - tumors of the central nervous system. The results of ST treatment are significantly worse than those of primary tumors. Thus, of 64 patients with ST, 46 (71.9 %) are alive, death from ST progression was noted in 18 (28.1 %) cases.Conclusion. Improvement of modern treatment protocols aimed at reducing the indications for radiation therapy and cumulative doses of alkylating agents, along with the development of effective follow-up programs for children cured of hematological malignancies, will probably help reduce the ST incidence.

Background. Secondary malignancies in pediatric cancer survivors is an actual problem in modern oncopediatry. Alkylating agents and topoisomerase II inhibitors used for primary tumors treatment, induce secondary acute myeloid leukemia (sAML), which treatment results are unsatisfactory.Objective. By predicating on literature and own data to evaluate clinical and biologic features and therapeutic potential of pediatric sAML.Materials and methods. Six patients (age 7–16 years) with sAML were enrolled the study from June 1998 to December 2016. Follow up until September 2020. Primary tumors, which therapy could induce sAML were acute lymphoblastic leukemia, Burkitt lymphoma, germ cell tumor, osteosarcoma, nephroblastoma.Results and conclusion. From 6 patients, included in the study, 2 are alive (+58 and +67 months after allogenic stem cell transplantation), that match global data. Fludarabine-containing regimens and allogeneic hematopoietic stem cell transplant could be a method of choice for this unfavorable group of patients.

Treatment of acute lymphoblastic leukemia (ALL) in children during the last 50 years has changed significantly, which has increased the survival of patients from 10–15 % in the early 60s to 80–85 % by the mid-2000s. Such results have been achieved through the development of new polychemotherapy regimens, the introduction of neuroleukemia prophylaxis, the strengthening of standard chemotherapy by increasing the dose and / or frequency of chemotherapeutic drugs administration, and the definition of criteria for patient stratification into prognostic risks groups and the development of principles of risk-adopted therapy.However, inspite of the overall success of pediatric acute lymphoblastic leukemia therapy, some variants of acute lymphoblastic leukemia associated with poor prognosis, especially acute lymphoblastic leukemia with BCR-ABL1 and MLL rearrangements. Besides the prolonged persistence of minimal residual disease is also an unfavorable prognostic factor requiring therapy intensification.In the current issue we present the main steps in the evolution of programmed chemotherapy of children with acute lymphoblastic leukemia. Great attention was paid for modern risk-stratifying criteria with an emphasis on minimal residual disease.

Background. Bendamustine is one of the main drugs included in the arsenal of cytostatic agents that are used in oncohematology. In Russia, the drug was registered at the end of 2010 under the commercial name Ribomustin (company Astellas). At the end of 2018, two national generics of bendamustine appeared on the Russian market – Rozustin® (Rafarma) and Kovada (Biocad).Materials and methods. In 2019 the department of hemoblastosis chemotherapy of the N. N. Blokhin National Medical Research Center of Oncology received the drug bendamustin (Rozustin®) (Rafarma, Russia). This article presents the first experience of using Rozustin® in patients with various lymphoproliferative diseases. Most often, the drug was used for relapsed or refractory classical Hodgkin’s lymphoma.Results and conclusion. The high effectiveness, acceptable toxicity profile compared to alternative “salvage” regimens, ease of implementation, and the possibility of a full collection of hematopoietic stem cells followed by high-dose chemotherapy and autologous stem cell transplant, confirm the good potential of the combined program with the inclusion of the drug bendamustine (Rozustin®).

Erdheim–Chester disease (ECD) is a rare and frequently neglected disease, usually with a poor prognosis. The first two cases of ECD were reported by Austrian pathologist: Jakob Erdheim and his apprentice student William Chester in 1930. The etiology and disease incidence are unknown. One of the main components of this disorder is a chronic uncontrollable inflammation. Clinical manifestations of the disease can be very different. ECD affects predominantly adults, usually male population. There is no effective treatment developed yet. In 2016 ECD was classified as histiocytic neoplasm by the World Health Organization and was categorized as “tumors of histiocytes and dendritic cells”. More than half of patients testing positive for the BRAF mutation. There is a Erdheim–Chester Disease Global Alliance (ECDGA), which try to unite and provide with information about diagnostics and treatment of this rare disease both patients and doctors. Today, there are 571 registered patients and only one from Russia. The final diagnosis is made on the basis of histological finding such as infiltration with foamy histiocytes, signs of inflammation and Touton giant cells. Immunohistological analysis is usually CD68 and XIIIa positive. There are radiological finding indicating a possible association with the disease. There is this specific, almost pathognomonic scintigraphic picture of the skeleton, “coated” aorta, “hairy kidney” patterns on computer tomography. We demonstrate a clinical case of a patient with a newly diagnosed ECD with bone and connective tissue involvement, with manifestation of this disease more than 10 years ago. It took four months to make the final diagnosis. There were three biopsies and a wide range of other diagnostic procedures.

Background. Currently, overall survival rate for pediatric patients with acute myeloid leukemia (AML) do not exceed 70 %. The intensity of modern AML chemotherapeutic programs has reached its limit, and further chemotherapy dose escalation for treatment results improvement is impossible, because it fraught with life-threatening complications. It is investigating a new ways of tumor treatment for improvement of AML patient’s survival level: therapeutic efficacy of targeted and epigenetic drugs.Objective: to evaluate the efficacy of epigenetic drugs (azacitidine, decitabine, all-trans-retinoid acid and valproic acid) in combination with AML-BFM 2004 protocol for treatment of pediatric AML.Materials and methods. 80 patients with primary AML diagnosis were enrolled the study. Age was ranged from 8 months to 17 years (median 6.7 ± 0.6 years). From June 2012 to January 2018 all patients were subdivided in two treatment groups. 1st group included 34 patients treated with NII POH AML 2012 protocol, 2nd group – 46 patients treated by AML-BFM 2004 protocol.Results. 3-year relapse-free survival in 1st group, regardless of prognostic risk group, was 66.7 ± 11.7 %, 2nd group – 68.9 ± 9.9 %. Eventfree survival (EFS) for patients from 1st group was 66.7 ± 11.7 %, form 2nd group – 50.4 ± 10.2 %. Overall survival in 1st group was 66.7 ± 14.3 %, 2nd group – 66.9 ± 7.5 %. For patients with unfavorable risk from 1st treatment group 3-year relapse-free survival was 69.1 ± 11.9 %, 2nd – 64.9 ± 11.3 % (p = 0,8). EFS – 69.1 ± 11.9 and 44.8 ± 11.3 % respectively (p = 0,13). 3-year overall survival for patients with unfavorable risk group was 69.4 ± 14.6 and 64.4 ± 7.9 % in 1st and 2nd treatment groups respectively.Conclusion. The efficacy of decitabine in “window” regimen was higher in contrast to azacitidine; epigenetic therapy with AML-BFM 2004 protocol allow us to achieve a higher EFS, because of induction mortality and infection-related death decrease – EFS in 1st group was 16 % higher than in 2nd. Besides, EFS in unfavorable risk group, who treated with epigenetic drugs, was 25 % higher – 69.1 ± 11.9 % and 44.8 ± 11.3 % in 1st and 2nd groups respectively (p = 0.13). Nevertheless, overall survival in both groups was the same – 66 % (1st – 66.7 ± 14.3 % and 2nd – 66.9 ± 7.5 %).

The results of treatment of acute myeloid leukemias (AML) in children remain unsatisfactory. Modern therapeutic programs with hematopoietic stem cell transplantation allow us to get 5-year overall survival rate of 65 % in primary patients. For patients with relapses or refractory AML, 5-year overall survival is about 35 %.This article presents the possibilities of chemotherapy and hematopoietic stem cell transplantation in the treatment of AML. The possibilities of epigenetic, immune, and cellular therapy are presented for pediatric AML. Special attention is paid to targeted drugs that only beginning to be used in the complex therapy of AML.

Despite the development and active use of modern high-effective therapeutic protocols for pediatric non-Hodgkin’s lymphomas (NHL), treatment results of relapses and refractory disease are unsatisfactory. In the current issue international practices and own experience in relapsed/refractory pediatric NHL are presented: lymphoblastic lymphomas, anaplastic large cell lymphoma, and heterogeneous group of mature B-cell lymphomas. Chemotherapy protocols, results of nelarabine, rituximab, crizotinib, brentuximab vedotin, stem cell transplantation use for relapsed/refractory pediatric NHL treatment are presented. In 27 relapsed NHL patients treated inN.N.BlokhinNationalMedicalResearchCenterof Oncology, overall survival was 29.1 ± 7.9% (median follow-up 56.3 ± 14.4 months). Primary refractory NHL cases were fatal. Own and literature data make it necessary further study of new therapeutic approaches aimed at improvement of results in relapsed/refractory NHL.

In this article a rare case of monosystem form of congenital Langerhans cells histiocytosis (LCH) in 3 weeks of age girl was described. Local lesion of oral mucosa of the infant with LCH was first described. Morphological, immunological and clinical features of this rare disease have been characterized. Authors concluded that timely diagnostics is very important to risk-adapted therapy at children with LCH.