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Primary cutaneous lymphomas are quite rare in children. Clinical and histopathological manifestations of these diseases in children differ significantly from those in adults. Due to their rarity and complex clinical presentation, diagnosis may take long time. Mycosis fungoides (MF) is the most commonly diagnosed form of primary cutaneous lymphomas in childhood. There are no clinical guidelines for the treatment of children. Literature data on MF variants in children are scarce; the largest study includes 34 patients who were diagnosed on average 4 years after the onset of the first symptoms. In the present article we describe a clinical case of MF in an 11-year-old child with an 8-year history of multiple lesions of the skin and scalp. The patient's parents gave their consent to the use of their child's data, including photographs, for research purposes and in publications. The aim of our article is to demonstrate the problems in the diagnosis of the disease, especially at an early stage, because its symptoms may be similar to those of many common pediatric inflammatory skin conditions.

Nijmegen breakage syndrome (NBS) and ataxia-telangiectasia (AT; Louis–Bar syndrome) are primary immunodeficiencies (PID) associated with chromosome instability and DNA repair defects that predispose individuals to an increased risk of various malignancies. In our study, we retrospectively analyzed clinical characteristics and outcomes of 28 cancer cases in 14 patients with AT and 10 patients with NBS who had been treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology between January 2007 and December 2022. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The most common type of malignancy was mature B-cell non-Hodgkin lymphoma (B-NHL) (42%), with diffuse large B-cell lymphoma (DLBCL) accounting for 91% of all B-NHL cases. Other cases included T-cell acute lymphoblastic leukemia (ALL) (n = 3), B-cell ALL (n = 2), Hodgkin lymphoma (n = 3), NK/T-cell lymphoma (n = 1), T-cell lymphoblastic lymphoma (n = 1), peripheral T- cell lymphoma (n = 2), medulloblastoma (n = 1) epithelioid rhabdomyosarcoma (n = 1), T-cell prolymphocytic leukemia (n = 2). A total of 4 patients were diagnosed with second malignancies (2 children with AT and 2 children with NBS. The diagnosis of PID was suspected or confirmed before the initiation of cancer therapy in 62% of AT patients and in 100% of NBS patients. Treatment was given in accordance with standard protocols with chemotherapy dose modifications. A total of 93% of patients with AT and 80% of patients with NBS required dose reduction. The level of response was quite high: 81% of patients with AT and 58% of patients with NBS achieved complete remission. According to our data, the use of reduced-dose chemotherapy regimens helps to achieve an acceptable toxicity profile without reducing the overall effectiveness of treatment.

Today, treatment results for acute lymphoblastic leukemia (ALL) look encouraging, yet 10–15% patients still end up relapsing. The success of relapse treatment is directly dependent on whether or not a tumor clone has been completely eradicated before hematopoietic stem cell transplantation (HSCT). Immunotherapy made it possible to achieve minimal residual disease (MRD) – negative remission even in refractory patients. One example of such immunotherapeutic agents is inotuzumab ozogamicin (InO), an anti-CD22 monoclonal antibody conjugated to the cytotoxic agent calicheamicin. We included 17 patients under the age of 18 with relapsed or refractory precursor B-cell ALL (pre-B ALL) who had been treated with InO at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of Russia from 01.10.2016 to 01.09.2022. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The efficacy of the therapy was assessed based on the patients’ morphological response, MRD negativity and overall survival. Treatment toxicity was assessed according to CTCAE 5.0 (Common Terminology Criteria for Adverse Events). Statistical analysis was performed using the XLSTAT 2016 software. The majority of the patients (75%) responded to the therapy. MRD negativity was achieved in 41.2% of the study patients. The one-year overall survival rate was 40.3% (95% confidence interval 14.8–65.7). The treatment was well tolerated but 33% of the patients treated with standard-dose InO and subsequent HSCT developed veno-occlusive disease/sinusoidal obstruction syndrome. In our study, we demonstrated the high efficacy of InO both when used as a rescue therapy in patients with relapsed/refractory pre-B ALL and as a bridging therapy in patients before HSCT.

The effectiveness of treatment for children with B-cell non-Hodgkin lymphomas (B-NHL) has reached 85–90% after the introduction of modern risk-adapted treatment regimens that involve risk group stratification based on tumor stage. Bone marrow involvement is traditionally evaluated using quantitative morphological analysis of tumor cells which has, however, a lower sensitivity compared to molecular genetic methods. In our study, we used next generation sequencing (NGS) to identify tumor-specific V-(D)/J-rearrangements of immunoglobulin genes which can be used as a marker for the evaluation of minimal disseminated disease (MDD) in children with B-NHL. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Here we demonstrated that NGS allows detection of bone marrow involvement at a sensitivity of 10–6 in patients with Burkitt lymphoma, in whom standard morphological analysis failed to reveal the presence of tumor cells. The detection of molecular MDD can improve tumor staging and risk stratification in children with B-cell non-Hodgkin lymphomas.

Clinically significant myocardial infiltration by blast cells is a rare occurrence in acute leukemia. Heart failure rate in children with hemato-oncological diseases is unknown. Here we report a clinical case of an 8-year-old female patient with B-cell acute lymphoblastic leukemia as well as heart failure that resolved during specific therapy for the cancer. The patient's parents gave consent to the use of their child's data, including photographs, for research purposes and in publications.

Rosai–Dorfman disease (RDD) is a rare histiocytic disorder, which occurs at any age, can affect almost any organs and tissues, does not have pathognomonic symptoms and could be confirmed only by histological examination of the affected tissue. The article describes the successful treatment of a child with RDD with lymph nodes, nasopharynx, subcutaneous tissue, spleen and bones involvement, by multistep surgical treatment and chemotherapy. A review of the literature is provided, including recommendations for the examination and treatment of patients with RDD. The patient's parents agreed to use the information, including the child's photo, in scientific research and publications.

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Despite remarkable improvements in the treatment of pediatric acute lymphoblastic leukemia over last years, relapse still carries a poor prognosis with considerable morbidity and mortality. New immunotherapeutic approaches will change the way we treated our patients and the results we had. Blinatumomab is a bispecific T-cell-engaging antibody indicated for the treatment of relapsed/refractory B-cell lymphoblastic leukemia. The use of Blinatumomab in relapsed B-cell ALL has shown promising effects, especially as a bridging tool to hematopoietic stem cell transplantation. The therapy results for patients in the high risk group remain far from optimal due to refractoriness to chemotherapy, death from infectious complications, as well as acute chemotherapy toxicity. This article demonstrates the results of our experience of using Blinatumomab in children with the high-risk group relapsed B-cell ALL treated according to the ALL-REZ 2016 protocol. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The efficacy and toxicity of innovational blocks with the use of fludarabine and clofarabine with subsequent Blinatumomab infusion are shown. And we present the efficacy of autologous CD3+ lymphocytes infusion once a week during the continuous blinatumomab therapy. Also we demonstrate the results of using Blinatumomab for the treatment of patients with refractory to the first line therapy relapsed B-lymphoblastic leukemia and patients with a second relapse of B-cell ALL. The first line therapy in these patients was carried out according to the ALL-REZ 2014 protocol. Our results show an improved reduction in minimal residual disease in patients with refractory relapsed B-cell ALL as well as an increased event free survival in children with the high-risk group relapsed B-cell ALL.

Progressive transformation of germinal centers (PTGC) is a benign reactive lymphadenopathy, which can be an independent disease or occur in association with other lymphomas, the most common variant of which is nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). To date, it has not been definitively clarified how PTGC and NLPHL are interconnected, despite the abundance of works presented on this topic. PTGC may precede NLPHL, occur synchronously with it, or develop after a course of therapy in patients with NLPHL. Despite similar clinical and morphological features, the approach to the treatment and management of patients is different. In the case of NLPHL, one of the therapeutic options is chemotherapy, which is not used in patients with PTGC. This article presents a clinical case of partial lymph node lesion of NLPHL associated with PTGC, on the example of which the main issues of differential diagnosis of PTGC and NLHLP will be considered. The patient's parents gave their consent to the use of their child's data, including photographs, for research purposes and in publications.

Acute lymphoblastic leukemia (ALL) with translocation t(17;19)(q21-q22;p13) TCF3::HLF (E2A::HLF) accounts for less than 1% of childhood B-lineage ALL. Since the first description, patients with this type of ALL are stratified into high-risk group. The disease often has a unique clinical presentation with disseminated intravascular coagulation and hypercalcemia, that are uncommon in other types of B-lineage ALL. This type of ALL is characterized by an extremely poor prognosis despite intensive treatment and hematopoietic stem cell transplantation (HSCT) in the first remission. In the last decade, some new data on the mechanisms of leukemogenesis in this type of ALL made it possible to come closer to understanding the reasons for the high refractoriness to chemotherapeutic agents. Along with the reports on the possible effectiveness of the BCL-2 (venetoclax) and Aurora kinase A (alisertib) inhibitors in this type of ALL, cellular immunotherapy (various chimeric antigen receptor (CAR)-T cell constructs), anti-CD19 (blinatumomab) and anti-CD22 (inotuzumab ozogamicin) monoclonal antibodies appear promising in the treatment of this disease. To date, there are neither published data on direct comparisons of the effectiveness of these methods nor specific recommended therapy protocols for these patients. It is also unclear if the new therapeutic approaches can completely replace HSCT or they only increase relapse-free survival after it. Here, we review the data on this translocation published in the medical literature and present a case report of a 3-year-old boy with this type of leukemia, who did not respond to four-component induction therapy according to the ALL-MB 2015 Protocol and received anti-CD19 CAR-T therapy with the achievement of the first MRD (minimal residual disease)-negative remission, which lasted 11 months. After MRD-relapse and unsuccessful attempt at therapy with autologous CD19/CD22 CAR-T cells, the patient developed an extended isolated bone marrow relapse. He achieved the second MRD-negative remission after reinduction therapy with inotuzumab ozogomycin and received allogeneic HSCT from a related donor. At the time of writing, the patient is in complete molecular remission for 16 months after transplantation. The patient's parents have consented to the use of de-identified clinical information and photos of the patient in scientific research and publications.

This paper presents the results for the patients with acute lymphoblastic leukemia (ALL) from the high-risk group (HRG) treated according to the ALL-MB 2002 Protocol. The registration phase of the study was performed from 15.04.2002 to 01.01.2008. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. The study involved 36 departments (centers) of pediatric hematology/oncology in Russia and Belarus. One hundred and ten primary patients with ALL aged 1 to 18 years who met the criteria for high risk group, were analyzed: 29 patients with t(9;22), 11 patients with t(4;11), and 70 patients without stratifying genetic abnormalities who did not achieve remission by day 36 of induction therapy (16 patients from the standard risk group and 54 patients from the intermediate risk group, at initial). Median follow-up was 10.75 (8.6–13.8) years. First remission (CR1) was achieved in 80.9% of patients. 37.27% of patients relapsed, 51.22% of relapses were very early. The proportion of isolated bone marrow relapse was 73%, while isolated central nervous system relapses were observed in 4.55% of the cases. None of the patients developed a secondary tumor, 5.45% of patients were lost from follow-up. Only 15.7% of patients with CR1 received allogeneic hematopoietic stem cell transplantation. Only half of the patients with Ph-positive ALL received treatment with tyrosine kinase inhibitors. In total, 26.36% of patients remain in CR1. Overall and event-free survival were 32.9 ± 4.6% and 31.5 ± 4.5%, respectively. The cumulative risks of relapses and treatment-related mortality were 37.6 ± 4.3% and 20.9 ± 3.8%, respectively. There were no significant difference in the initial parameters and responses to therapy between the subgroups of patients. Overall and event-free survival were the highest in patients with ALL with t(4;11): 54.5 ± 15% and 45.5 ± 15%, respectively. The lowest overall and event-free survival were observed in the subgroup of patients without stratifying anomalies who did not achieve remission on day 36: 29.1 ± 5.6% and 27.1 ± 5.3%, respectively. The cumulative risk of relapse was the highest in patients who did not respond to induction therapy (42.9 ± 5.2%). The cumulative risk of treatment-related mortality was the highest in patients with Ph-positive ALL (31.0 ± 8.6%). The 5-year overall survival of patients with ALL relapse after high-risk therapy was extremely low – 7.7% (95% confidence interval 0–16.1), median overall survival after relapse in this group was only 187 days. This indicates that the options for second-line therapy of high-risk patients were severely limited at the time of ALL-MB 2002 study, because they included only chemotherapeutic strategies.

This study presents the clinical and laboratory data of 50 patients with ataxia-telangioectasia syndrome (AT) (Louis-Bar syndrome) treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (Moscow, Russia) between 2012 and 2021. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. We found that the patients experienced a significant diagnostic delay (the median delay in diagnosis was 4.5 years), although the first typical symptoms of AT were present at an earlier age (the median age was 1.5 years). The majority of patients showed laboratory signs of immunodeficiency, yet only 24% of the children developed severe infections. However, lung infections resulted in bronchiectasis in 16% of the patients and were the cause of death in 4/10 cases. Fifty-two percent of the patients had autoimmune complications, including interstitial lung disease and skin granulomas, and 24% of the patients developed malignant neoplasms. Of patients who underwent testing, 85% had KREC and/or TREC levels below the cutoff values used for neonatal screening of primary immunodeficiency disorders in Russia, which suggests that the majority of AT cases could be diagnosed by neonatal screening. Early diagnosis, multidisciplinary approach and high clinical suspicion for neoplastic manifestations are crucial for the successful management of AT.

B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin’s lymphoma (cHL) is a rare malignant disease that develops from mature B cells. This disease was first recognized as a distinct entity in 2008. It is most common in the 20 to 40 age group and rare in children. Currently, there are no clear criteria for diagnosis and standard therapy for such patients. According to the literature, it is possible to use treatment regimens applied for both aggressive B-cell lymphomas and Hodgkin's lymphoma. The addition of anti-CD20/CD30 targeted agent to standard therapy may be effective, given the expression of these markers by tumor cells. In this article, we present the clinical and morphological characteristics of patients with unclassifiable B-cell lymphoma with features intermediate between DLBCL and cHL, diagnosed at our center, including 4 patients at the onset of the disease in childhood. Patients and/or their legal representatives have consented to the use of information, including photographs, in scientific research and publications.

The five-year overall survival (OS) rate for pediatric Hodgkin's (HL) and non-Hodgkin's (NHL) lymphomas remains at 85–95% despite improvements in therapy regimens. The problem of establishing reliable prognostic factors that could help identify high- or ultra-high-risk patients is still unresolved. We performed a systematic literature review and meta-analysis of studies investigating the predictive value of baseline metabolic parameters of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in pediatric patients with lymphomas. We systematically searched the following databases: PubMed, Medline, Cochrane Library and Google Scholar. Six retrospective studies (309 patients) evaluating the effect of quantitative parameters derived from baseline PET/CT with 18F-FDG (maximum standardized uptake value (SUVmax), tumor metabolic volume (MTV), and total lesion glycolysis (TLG)) on OS and event-free survival (EFS) in children with HL and NHL were included in our analysis. We used the Cochrane ROBINS-I tool to assess the quality of studies; the relative risks (RR) for the studied outcomes were calculated with RevMan software, version 5.3. The overall analysis showed that high MTV was associated with a six-fold increase in the relative mortality risk (RR 6.18 (3.15–12.11), p < 0.001) and a more than 5-fold increase in the risk of relapse/progression (RR 5.68 (3.21–10.07), p < 0.001). High values of TLG were associated with an eight-fold increase in the risk of mortality (RR 8.06 (3.35–19.39), p < 0.001) and worse EFS (RR 5.75 (2.99–11.06), p < 0.001). Our results will enable oncologists to expand existing risk assessment systems and improve their predictive effectiveness by using MTV and TLG parameters.

Lymphocyte-predominant Hodgkin's lymphoma (NLPHL) is a unique variant of Hodgkin's lymphoma (LH) with a relatively good prognosis. The tumor differs markedly from classic LH and is one of the forms B cell lymphoma. Despite the indolent course, it has a tendency to multiple and often late relapses. Microscopically, the tumor has 6 distinguishable morphological patterns. Despite the prevalence in all age groups, most of the original studies were performed among adult patients, while there are only several publications among the children's population. The aim of this study – retrospective analysis pediatric group of the NLPHL, evaluate the prognostic implication of histopathologic variants. Сomparing our own data with another study groups. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Study was included the biopsies aged 3 to 18 years (median 10.5 years) of 28 patients with NLPHL from the archive by Department of Pathology Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology from 2014 to 2020. The tumor more commonly affects males (20 boys and 8 girls, male-female ratio, 2.5:1). Complete clinical information was available in 24 patients. The clonal molecular assays were performed in 2 cases of relapse/progression of the disease. The Fisher's exact test was used to compare and evaluate the statistical significance of the differences in groups of patterns. There were no significant differences between typical patterns and variants, probably due to the small number of the patients. Further research will create a predictive scale for stratification by the risk groups. In cases of poor response to therapy, there is a risk that the pattern will turn into a prognostically more unfavorable variant.

Lymphoblastic lymphoma (LBL) is a rapidly progressive, malignant disease from T and B progenitor cells. Lymphomas from T cell precursors (T-LBL) account for up to 80% of all LBLs. Despite the rather rare occurrence of T-LBL, the relapsing and refractory course of this disease is an actual problem. Programs for the treatment of relapses and refractory forms of T-LBL are currently being actively developing. The role and place of targeted drugs in the multimodal T-LBL relapse strategy is determined. Further fundamental research is aimed at overcoming drug resistance, studying the molecular genetic mechanisms, tumor cell signaling pathways, which will improve treatment outcomes and survival. Based on clinical case the authors will be considered clinical features of relapses and refractory form of T-LBL and possible methods of treatment. Parents gave their consent to use information about the child, including fotos, in the article.