Problems of clinical and morphologic diagnosis of orolabial melanosis in children

Pigmented neoplasms of the skin and mucous membranes are a heterogeneous group of benign and malignant neoplasms, some of which are extremely rare in the practice of pediatric oncologist. Orolabial melanosis refers to a benign pigmented pathology of the skin and mucous membranes, requires differential diagnosis with ephelids, melanoma, and when localized on the tongue – with pigmented fungiform papillae of the tongue.This article presents a clinical case of orolabial melanosis with localization on the tongue in a 9-year-old child that was not previously described in the domestic literature. The clinical, dermatoscopic, immuno-morphological and differential diagnostic features of this pathology are described in detail.

Treatment of acute lymphoblastic leukemia in children by ALL IC-BFM 2002 protocol: results of multicenter retrospective study

By the whole history of pediatric acute lymphoblastic leukemia (ALL) treatment protocols development, one of the World ideologist of original science-based therapeutic approaches was German group BFM (Berlin–Frankfurt–Münster). It is not surprisingly that modern ALL treatment protocols, developed by BFM group are high-effective and use in many countries. Understanding the probability of recovery of overwhelming ALL patients majority treated by ALL IC-BFM 2002 protocol, the Scientific-Practical Board of Ministry of Health of Russia in 2020 adopted a protocol as clinical recommendation for pediatric ALL treatment (ID:529).It the current issue BFM ALL treatment protocols evolution is presented and first Russian multicenter experience in pediatric ALL treatment by ALL IC-BFM 2002 protocol. It was 408 pediatric and adolescents patients with primary ALL included the study. All of them were treated by ALL IC-BFM 2002 protocol from 01.11.2003 to 12.05.2021. Survival rate was estimated on 01.06.2021.ALL IC-BFM 2002 demonstrated a high efficiency in multicenter retrospective study. 15-year event-free survival was 83.7 ± 2.1 %, relapsefree survival – 88 ± 1.8 % and overall survival – 93.4 ± 1.4 %. So, ALL IC-BFM 2002 protocol could be realized in Russian clinics and give results similar to world’s leading medical centers.

A review of pharmacogenetic aspects of methotrexate and 6-mercaptopurine toxicity in pediatric acute lymphoblastic leukemia treatment

Significant progress in the treatment of acute lymphoblastic leukemia (ALL) in children has resulted from the development of effective chemoand supportive care therapy protocols. The vector of further research is aimed at reducing toxicity and long-term side effects. The study of pharmacogenetic aspects of toxicity of the main drugs used in the treatment of ALL – methotrexate and 6-mercaptopurine – allowed to identify oligonucleotide polymorphisms that correlate with the concentration of the drug in blood, toxic effects and the risk of relapse of ALL. The clinical administration of pharmacogenetic methods remains a challenging task, requiring additional research, which will make it possible to individualize the ALL therapy on the basis of the results of molecular profiling.

Transpupillary laser thermotherapy of retinoblastoma

Introduction. Despite the fact that transpupillary thermotherapy (TTT) is one of the main local methods of small retinoblastoma (RB) destruction, only a few studies have been published on the use of this method, and they are devoted only to certain aspects of the application of TTT.Purpose of the study – to evaluate the effectiveness of TTT in the treatment of children with RB.Material and methods. In the period from 2011 to 2020, 177 children (224 eyes, 1156 tumors) with RB were treated by TTT. Of these, 99 (56 %) patients were boys, 78 (44 %) – girls. The mean age at the time of treatment was 16.8 months (from 0 to 86 months). Bilateral RB was observed in 128 (72.3 %) patients, monolateral – in 49 (27.7 %). In 51 (28.8 %) cases, TTT was performed on an only eye. TTT was performed on eyes that had RB of groups A (n = 43; 19 %), B (n = 81; 36 %), C (n = 31; 14 %), D (n = 63; 28 %), E (n = 6; 3 %). In total, 1156 tumors were treated by TTT. 488 (42 %) tumors were localized post-equatorially (of which 27 were located juxtapapillary, 23 – in the macular zone, 22 – paramacular). 668 (58 %) foci had pre-equatorial localization (on the middle and far periphery of the fundus). The number of foci in one eye varied from 1 to 48 (mean – 5). The mean tumor thickness was 1.1 mm (from 0.2 to 4.5), the mean base diameter was 2.2 mm (from 0.3 to 13.4). TTT was performed using a diode laser with the following parameters: wavelength – 810 nm, spot diameter – 1200 microns, power from 200 to 800 mW (mean – 350 mW), exposure-from 3 to 15 s in the application mode, and continuous in the scanning mode.Results. Complete tumor regression after TTT was achieved in 92 % of cases (1064 tumors). Incomplete regression of the tumor with stabilization was achieved in 0.7 % (8 tumors). The average number of TTT sessions to achieve full regression was 1.7 (from 1 to 10). Complete tumor regression after 1 TTT session was achieved in 54 % of cases (622 tumors), after 2 sessions – in 11 % (132 tumors), after 3 sessions – in 7 % (85 tumors), after 4 or more sessions– in 19 % (225 tumors). In 7 % of cases (82 tumors), due to the progression of the tumor, other treatment methods (brachytherapy, cryotherapy, stereotactic radiosurgery) were applied. 209 (93 %) eyes were preserved. 15 (7 %) eyes were enucleated due to continued tumor growth, total retinal detachment, vitreous hemorrhage, or subatrophy of the eyeball. The mean follow-up after TTT was 35.5 months (from 3 to 112 months).Conclusion. TTT is a highly effective method of RB treatment and can be used for destruction of small primary foci of both post-equatorial and pre-equatorial localization, residual tumors after inefficiency of other local methods. TTT is also effective in the treatment of large cavitary tumors located in functionally significant areas of the retina.

Dental disorders in patients recovered from malignant neoplasms in childhood

During the development of the bodyʼs homeostatic systems, anticancer drugs and radiation affect both tumor cells and healthy tissues. Damage to tissues with low potential for restorative functions, such as teeth, leads to a high probability of irreversible changes. The purpose of this literature review is to provide information on dental defects resulting from anticancer treatment. The most common anomalies in the development of teeth include a violation of the number, size, shape, mineralization of teeth, defects of dentin and enamel. The effect of a number of chemotherapeutic drugs has been studied in animal models and include a deficiency and thinning of the roots of the teeth. Irradiation leads to a wider spectrum of dental pathology: the integritation of the teeth changes, craniofacial dysmorphism, post-radiation mandibular hypomobility, damage to the salivary glands, the risk of developing osteoradionecrosis. The extent and severity of these effects depends from the child's age type of tumor and the radiation dose. The stage of tooth development is critical. Patients who received hematopoietic stem cell transplantation (HSCT) before the age of 3 have a higher risk of dental disorders and anomalies in the development and growth of the face. Radiation therapy plays a leading role in the formation of caries. The study of the long-term effects of radiation therapy, chemotherapy, HSCT on the development of dental complications is of interest to identify the most vulnerable groups of patients in order to ensure the possibility of early intervention and improve the quality of life.

Treatment of Ewingʼs sarcoma in children and adolescents: new vision

Introduction. Over the past decades, a significantly greater understanding of the morphology and molecular biological characteristics of tumors of the Ewing sarcoma family (ESFT) has been achieved. More than 70 % of relapses occur within 2 years from the date of diagnosis. In about 2/3 of cases, relapse occurs in distant places; this type of relapse is especially common in patients who initially have metastases. On the contrary, isolated local metastasis most often (in 1/5 of cases) occurs in patients with a localized form of the disease. In half of the patients, a relapse of the disease was detected during a routine examination, was asymptomatic and was a chance find.Purpose of the study – to evaluate the effectiveness of anti-relapse treatment in patients with ESFT, to develop an algorithm for a personalized approach, to improve the results of overall and relapse-free survival in children and adolescents with ESFT.Materials and methods. Our study included patients with a confirmed diagnosis of Ewing sarcoma (ES), who received treatment from 2008 to 2019. The analysis of follow-up data was closed on 19.02.2021. The study included 274 patients aged 6 months to 18 years, the average age was 11.6 years. Up to 1 year in our study there were 2 children. Twelve (4.3 %) patients went out of follow-up within 2 to 9 months from the start of treatment; we did not include them in the subsequent analysis. Analyzed were 262 patients with ES who received treatment according to the protocols at the Research Institute of Pediatric Oncology and Hematology of the N.N. Blokhin National Medical Research Center of Oncology. A relapse of the disease was revealed in 48 (18.3 %) children out of 262 – the study group; 58 (22.1 %) patients showed disease progression during treatment. In 70.8 % (34/48) patients had an isolated relapse, in 14 (29.2 %) cases – a combined one. The defeat of only the lung tissue with a relapse of the disease occurred in 19/48 (39.6 %) cases, local relapse without metastasis – 7/48 (14.5 %) cases. In general metastatic lung disease occurred in 66.6 % of cases. The defeat of the brain and lymph nodes occurred in 4 %. Most of the patients were in the group from 11 to 17 years, inclusive – 38/48 patients, which amounted to 79 %. All 48 patients from the study group received anti-relapse therapy depending on the duration of the disease relapse. For late relapses the primary treatment regimen was used: alternating courses of chemotherapy with vincristine/doxorubicin/cyclophosphamide and etoposide/ifosfamide. In early relapses two regimens were most used: vincristine/topotecan/cyclophosphamide and vincristine/irinotecan/temozolomide (VIT). The positive response rate with the antirelapse VIT regimen was 60 %, and the time to progression was 7.6 months. With the topotecan regimen the response rate was 45 % and the time to progression – 7 months.Results. The overall survival (OS) rate of patients when a relapse was detected was significantly (p £ 0.05) higher when compared with the group of patients who had progression of the disease, which is associated with the effect of anti-relapse chemotherapy. When analyzing OS of patients with ES it should be noted that the 5-year survival rate of all patients (n = 262) was 66.3 ± 3.3 %, compared with the group of patients with confirmed relapse (n = 48) – 53 ± 8.1 %. The median in the group of patients with relapse was 39.3 months. The follow-up time in the group with recurrent ES disease averaged 52.2 ± 32.3 months (from 12.6 to 142 months). OS of patients was analyzed depending on the interval of disease recurrence. The Interval No. 1 was from the beginning of the main treatment to the first relapse, with a median of 37.2 months. Interval No. 2 – from the date of the first relapse to the date of the second relapse with a follow-up time of 58.8 ± 29.1 months (from 28.6 to 108 months), the median was not reached. The second relapse occurred significantly less frequently than the first relapse (p = 0.000001).Conclusion. The outcome for patients with recurrent ES remains poor, and a standard approach to their treatment has not yet been established. Standard first and second lines chemotherapy can be effective in most patients in terms of reducing symptoms and increasing the time to further progression, but complete remission remains hard to reach. Further multidisciplinary study of prognostic factors, effects of various treatment regimens and protocols, study of the inclusion of targeted drugs in the therapy program is required.

Giant cell reparative ethmoid granuloma: a clinical case with a review of the literature

Giant cell reparative granuloma (GCRG) is a rare benign tumor that develops in the first two decades of life. Data on the incidence of GCRG in children vary significantly depending on the number of observations and methods of statistical data processing. GCRG is more common in long bones, but rare cases of damage to the bones of the facial skeleton, which account for only 2–12 %, have been described. The etiological factors of GCRG are unknown, but genetic predisposition and intraosseous hemorrhages after an injury are the predisposing factors. Despite its benign nature, the process can be locally aggressive. Rapid invasive growth, complex anatomy of the base of the skull in childhood make surgical treatment in this place quite difficult. The clinical symptoms of ethmoid GCRG are nonspecific and depend on the site involved and the degree of local destruction. Distinctive morphological features of this neoplasm are the presence of multinucleated giant cells, cellular fibrous tissue and hemorrhages. Diagnostics of this disease includes endoscopic examination of the nasal cavity and nasopharynx, magnetic resonance and X-ray computed tomography of the skull base, paranasal sinuses with intravenous contrast, radioisotope research methods. We report a case of the development of GCRG in a 6-year-old child, along with the clinical picture, X-ray, scintigraphic and morphological data. The method of choice for the treatment of GCRG was its complete surgical removal.

The use of Jelonet dressings in the treatment of drug toxicity in autologous stem cell transplantation in children. Clinical case presentation

One of the complications arising at the stage of hematopoietic stem cell transplantation (HSCT) is skin lesions. This complication is quite common and represents an important diagnostic and therapeutic problem. The main cause of skin lesions in HSCT is drug toxicity, but also infectious lesions. Each of the complications can manifest itself in varying degrees, as well as be combined with others, having a significant negative effect on the patient’s condition, in severe cases posing a threat to the patient’s life. This paper presents a clinical case of a patient with treosulfan toxicoderma who was treated with JELONET dressings.

Features of the course of the gestational process with the carriage of genotypes F5L:G(1961)A and F2:G(20210)A and inheritance options

Aim of the study – to establish the features of inheritance of the F5L:G(1961)A and F2:G(20210)A genotypes and to assess their influence on the course and outcomes of pregnancy.Materials and methods. The object of the study was 70 mother–child pairs: 50 women, carriers of the F5L:G(1961)A mutation, and their children; 20 female patients, carriers of the F2:G(20210)A mutation, their children. Additionally, 18 families of women, carriers of the factor V Leiden mutation, in three generations were studied.Results. Carriage of the F5:(1961)GA and F2:(20210)GA genotypes in fetuses is associated with the risk of developing gestational complications in their mothers, which are primarily realized when the maternal laboratory phenotype is manifested. A higher frequency of occurrence of the minor allele A20210 of the FII gene was determined in children than in the older generation (p = 0,0006).

Immunotherapy by anti-GD2 antibodies in patients with primary high-risk neuroblastoma, primary resistant and relapsed disease: Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg experience

Introduction. The long-term event-free survival of patients with high-risk neuroblastoma (NB) receiving intensive complex therapy according to current russian standard do not exceed 40 %. Also, there is no standard tactics in patients with primary resistant and relapsed disease, most of them die due to disease progression. While, anti-GD2 immunotherapy (IT) proved to be effective in patients with high-risk NB, in Russian Federation this method is not generally available. There are currently two pilot studies ongoing in Raisa Gorbacheva Memorial Institute aimed to evaluate the effectiveness of anti-GD2 antibodies in high-risk NB patients.Aim of the study – describing a single-center experience of anti-GD2 IT in primary high-risk NB patients and patients with primary resistant and relapsed disease.Materials and methods. A total of 20 patients received anti-GD2 antibodies, 16 of them were included into pilot trials. The median age at IT initiation was 5 (3–17) years. In 13 cases the therapy was initiated in patients with high-risk disease after auto-HSCT, in 3 cases – in patients with 1st systemic relapse of primary resistant disease after 2nd-line therapy and haplo-HSCT, in 1 case – in patient with 2nd chemosensitive relapse after haplo-HSCT. Also, 3 patients with progressive chemoresistant disease received anti-GD2 antibodies as monotherapy (n = 1) or in combination with chemotherapy (n = 2) as salvage regimen.Results. Patients receiving anti-GD2 antibodies after auto-HSCT retain response to therapy in 11 of 13 cases with a median follow-up period of 15 (6–27) months, in 2 cases there was disease progression during or immediately after IT cessation. Both patients with disease progression responded well to salvage therapy. Two of 3 haplo-HSCT recipients with prior good response to 2nd-line therapy are currently in remission 16 and 36 months past haplo-HSCT, one patient progressed 55 months after transplantation. A patient with 2nd late relapse after haplo-HSCT currently maintains remission on IT. Both patients with chemorefractory progressive disease did not respond to IT and died due to disease progression. IT was characterized by acceptable toxicity. In most cases it was complicated by Gr 1–2 fever, rash or neuropathic pain effectively controlled by supportive therapy. However, three patients had signs of neurotoxicity requiring therapy termination in one case.Conclusion. Dinutuximab beta IT is characterized by acceptable toxicity. With a median follow-up of 18 (6–59) months the majority (14 of 17) patients receiving anti-GD2 antibodies as maintenance therapy after auto- or allogeneic HSCT retain response. However, we did not observe any response in patients with progressive chemorefractory disease.