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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.

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.

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.

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.

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.

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. 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. 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.