Background. Current chemotherapy protocols for T-cell acute lymphoblastic leukemia (T-ALL) allow achieving a 5-year overall survival of 60–90 %, but relapsed and refractory forms remain incurable situations.Aim. To determine the significance of immunophenotypic, cytogenetic and molecular markers in adult T-ALL patients receiving therapy according to the ALL-2016 protocol.Materials and methods. From December 2016 to June 2022, 113 patients with primary T-ALL were included in the study. Cytogenetic study was performed in 104 (92 %) patients; anomalies in the IKZF1 and NOTCH1 genes were investigated in 43 (38 %) patients.Results. The worst prognosis was in patients with ETP and near-ETP variants of T-ALL (3-year disease-free survival was 54 % in ETP group, 33 % in near-ETP group vs TI/II – 79 %, TIII – 89 %, TIV – 75 %). In early T-ALL variants, abnormal karyotype was most common (ETP – 80.7 %, near-ETP – 60 %). Aberrations in NOTCH1 gene were found in 53 % of cases (in 23 out of 43 patients), and no mutations were found in IKZF1 gene in our study. In the group with no NOTCH1 abnormalities, the overall survival was significantly worse than in the group with abnormalities (NOTCH1– – 52 % vs NOTCH1+ –81 %; p = 0.05).

Background. The effectiveness of therapy for acute T-lymphoblastic leukemia (T-ALL) and T-lymphoblastic lymphoma (T-LBL) has significantly improved over the past decades, including through the implementation of hematopoietic stem cell transplantation (HSCT). The Russian multicenter ALL-2009 study (ClinicalTrials.gov NCT01193933) showed that performing autologous HSCT (auto-HSCT) in patients with T-ALL/LBL improves long-term results. However, the study was non-randomized and the need for auto-HSCT in clinical practice requires careful study.Aim. To assess the significance of auto-HSCT in patients with T-ALL/LBL in the framework of ALL-2016 multicenter, prospective, randomized study (ClinicalTrials.gov NCT03462095).Materials and methods. The study included 109 adult patients with T-ALL/LBL (m:f 82:27). Median age was 31 (18– 52) years. T-ALL was diagnosed in 88 (81 %) patients, T-LBL in 21 (19 %) patients. All patients are treated according to the ALL-2016 protocol. Using the web platform, upon completion of induction therapy (+70 days), all T-ALL/LBL patients who achieved clinical and hematological remission were randomized to the auto-HSCT arm or chemotherapy alone (CT). Centralized monitoring of minimal residual disease (MRD) in bone marrow samples was performed by multicolor flow cytometry at the control points according to the ALL-2016 protocol. Statistical analysis was performed using SAS 9.4.Results. 87 patients with T-ALL/LBL were randomized: 44 to the auto-HSCT arm and 43 to the CT arm. Further analysis included 25 patients who underwent auto-HSCT and 36 patients receiving only CT. Three-year relapse-free survival in T-ALL is estimated at 62 % (auto-HSCT) vs. 81 % (CT) (p = 0.3422), and in T-LBL – 67 % (auto-HSCT) vs. 79 % (CT) (p = 0.59). MRD persistence on the +70th day of therapy according to the ALL-2016 protocol was determined in 40 % of patients (autoHSCT) and in 67 % (CT) (p = 0.057). In a multivariate analysis, it was determined that T-ALL from early T-cell precursor (ETP-variant) and MRD persistence after the end of II phase induction are the main risk factors for relapse in the treatment according to the ALL-2016 protocol.Conclusion. Performing auto-HSCT both in patients with T-ALL and T-LBL, and with MRD persistence on day +70 according to the ALL-2016 protocol did not improve long-term results. The development of new programs for the treatment of patients with MRD persistence, as well as the ETP variant of T-ALL, is of current interest.

Introduction. There are several forms of the L-asparaginase which are characterized by differences in the half-life, the spectrum of toxicity as well as other factors. Aim — to determine the incidence of different types of L-asparaginase toxicity in adult patients with Ph-negative acute lymphoblastic leukemia (ALL) treated according to the ALL-2016 protocol. Materials and methods . From December 2016 to February 2023 the multicenter prospective randomized study “ALL-2016” included 313 patients with newly diagnosed Ph-negative ALL. Information about the 256 patients who had toxicity of native L-asparaginase was entered into an electronic database. The ratio of men and women was 155:101. The median age was 32 (18–54) years. We analyzed 1253 courses of therapy that included the administration of L-asparaginase. Results . L-asparaginase toxicity and adverse reactions were diagnosed in 67 (26 %) of 256 patients. Of the 1253 courses, 102 (8 %) had complications associated with the administration of this drug. Grade 1–2 toxicity of L-asparaginase was diagnosed in 34 (51 %) patients: allergic reaction — in 6 (18 %), thrombosis of brachiocephalic veins associated with the installation of a central venous catheter — in 2 (6 %), increased pancreatic amylase in blood serum and diastase in urine, without clinical signs of pancreatitis — in 3 (9 %), lower protein-synthesis function of liver — in 23 (68 %), hepatotoxicity — in 15 (44 %). Grade 3–4 toxicity of L-asparaginase was diagnosed in 33 (49 %) patients, of which 22 (67 %) required discontinuation of the drug. The median of the development of complications of L-asparaginase was the third administration. None of the patients died as the result of the toxicity of native form of the drug. The 5-year overall survival (OS) and the probability of relapse (PR) in the group of patients in which L-asparaginase was discontinued at the stage of induction of remission and in the group of patients who continued L-asparaginase treatment at remission consolidation and maintenance therapy did not differ significantly: OS — 89 % vs 70 % (p = 0.0921), PR — 47 % vs 33 % (р = 0.8633). Conclusion. In adult patients, L-asparaginase withdrawal due to toxicity, in most cases, occurs at the stage of the remission induction. It is possible that the replacement of the native form the drug to the pegylated one in adult patients with ALL, in whom L-asparaginase is canceled at the stage of remission induction, improves long-term survival rates.

Introduction . The introduction of chimeric antigen receptor (CAR) T-cell therapy is a promising treatment of patients with relapsed or refractory (R/R) B-cell lymphoproliferative diseases (LPDs). Aim — to present the results of CAR-T-cell therapy of 6 adult patients with B-cell LPDs. Materials and methods . This is a pilot study conducted in adult patients with R/R or persistent minimal residual disease B-cell LPDs treated with CAR-T-cells. The study was approved by a local ethical committee of National Research Center for Hematology. Patients did not have alternative options for effective and safe treatment. All patients signed an informed consent. All patients were lymphodeplated with fl udarabine and cyclophosphamide for 4 days before the introduction of CAR-T-lymphocytes. Cytokine release syndrome (CRS) was prevented by tocilizumab on the day of CAR-T-cell administration. The effi cacy and safety of CAR-T-cell therapy was evaluated. Results . From 01.01.2020 to 01.01.2022, 10 CAR-T-cell infusions were performed for 6 adult patients (age 19–68 years, median — 32 years) with B-cell LPDs: 4 — R/R B-acute lymphoblastic leukemia, 1 — R/R diffuse large B-cell lymphoma, 1 — persistence of MRD in mantle cell lymphoma. In all patients with a R/R, median — 4 (2–5) lines of chemotherapy and/ or immunotherapy were performed before CAR-T-cell therapy. CD19 CAR-T-cells received 3 patients, CD19/CD22 CAR-Tcells — 2 patients, CD19 and CD20 CAR-T-cells received 1 patient. Autologous CAR-T-cells received 4 (66 %) patients, allogeneic CAR-T-cells received 1 patient, and one patient had two CAR-T-cell administrations — 1 autologous and 1 allogeneic. The median number of CAR-T-cells was 0.5 × 10 6 /kg (from 0.1 × 10 6 /kg to 3 × 10 6 /kg). In 7 (87.5 %) of the 8 cases after CAR-T-cell administration, overall response to therapy (complete or partial remission) was achieved, and complete remission was achieved in 6 (75 %) cases. Side effects were noted after 8 of 10 CAR-T-cell transfusions: CRS in 40 % (CRS 1 — 10 %, CRS 2 — 20 %, CRS 3 — 10 %), ICANS in 10 %, tumor lysis syndrome in 20 %, multi-organ dysfunction syndrome in 10 %. There were no lethal complications due to CAR-T-cell administrations. The median follow-up period was 6 (1–16) months. Of the 6 patients, 2 (33 %) died from relapses and progression of LPD. One (17 %) patient died in complete remission from infectious complications. Three (50 %) patients are observed till now. The median time of CAR-T-cell circulation was 33 (6– 60) days. Conclusion . CAR-T-cell therapy is a promising treatment for R/R B-cell LPDs and LPDs with persistence of MRD after cytoreductive therapy. This type of therapy requires a multidisciplinary approach.

Purpose. To evaluate the efficacy of transpupillary thermotherapy (TTT) in the treatment of cavitary retinoblastoma (Rb). Material and methods. In the period from 2014 to 2018, 15 children (16 eyes, 21 tumors) with Rb were treated by pigment inducing TTT. The average age at the time of treatment was 22.8 months. The binocular form of Rb was observed in 9 patients (60%), monocular – in 6 (40%). In 5 cases (33%) TTT was performed in monocular patients. In total, 21 tumors of post-equatorial localization of Rb were treated by pigment inducing TTT, 12 of which (57%) were located in functionally significant areas of the fundus. The mean tumor height was 2.8 mm, the mean basal diameter was 6.5 mm. TTT was performed using a diode laser with the following parameters: wavelength – 810 nm, spot diameter – 1200 microns, power from 300 to 800 MW, with continuous exposure until the whitening of the tumor appearance. Results. Local tumor control after organ-preserving treatment was achieved in 95% of the cases (20 tumors). Complete tumor regression after pigment inducing TTT was achieved in 81% of cases (17 tumors). In 9% of the cases (2 tumors), partial regression of the tumor with stabilization was achieved. In one case (5%), brachytherapy was performed due to the continued tumor growth. 14 eyes (88%) were preserved after organ-preserving treatment. 2 eyes (12%) were enucleated due to tumor progression. Complications after pigment inducing TTT were observed in one case (6%) and were represented by partial vitreous hemorrhage. The mean follow-up period after pigment inducing TTT was 35 months. Conclusion. Pigment inducing TTT is highly effective in the treatment of cavitary Rb. Key words: ophthalmology, retinoblastoma, transpupillary thermotherapy, cavitary retinoblastoma, laser treatment, pediatric oncology.

Introduction. Cryotherapy (CT) is one of the main methods of small retinoblastoma (Rb) treatment and remains the “gold standard” for the treatment of small tumors of pre-equatorial localization, however, the number of studies in the literature on this problem is small, and they are represented only by single studies.Purpose of the study – to evaluate long-term results of CT of Rb.Materials and methods. During the period from 2008 to 2021 CT was performed in 87 children (98 eyes, 169 tumors) with Rb. 49 (56 %) patients were boys, 38 (44 %) were girls. The average age at the time of treatment was 22 months (from 0 to 73 months). Bilateral RB was observed in 70 (80 %) patients, unilateral – in 17 (20 %). In 19 (22 %) cases, CT was performed on a single eye. A total of 169 tumors were treated by CT. Most of the treated tumors (138 foci, 82 %) had pre-equatorial localization (35 tumors – on the mid periphery and 103 tumors – on the far periphery of the fundus). 31 (18 %) tumors located postequatorially. The mean tumor thickness was 1.2 (from 0.4 to 2.9) mm, the mean basal diameter was 2.2 (from 0.9 to 4.9) mm.In the vast majority of cases (n = 78, 87 %), CT was performed with an incision of the conjunctiva and separation of the tenon capsule in the projection of the tumor, then a double application with an exposure of 60 seconds was carried out according to the “classic” technology (“freeze–thaw”). In 13 % of cases (n = 9), CT was performed transconjunctivally without a conjunctival incision. In all cases, carbon dioxide (–78 ºC) was used as a refrigerant.Results. Complete tumor regression after CT was achieved in 63 % of cases (106 tumors), of which in 91 % of cases (96 tumors) – after one CT session, in 8 % (9 tumors) – after 2 sessions, in one (1 %) case– after 4 CT sessions. In 10 % of cases (17 tumors) an incomplete regression was observed and subsequent transpupillary laser thermotherapy was performed. In 27 % of cases (43 tumors), continued tumor growth or recurrence of the tumor was detected, and therefore other methods of local treatment were used (brachytherapy, laser thermotherapy, intra-arterial and intravitreal chemotherapy). As a result of organ-preserving treatment, 90 (92 %) eyes were preserved, 8 (8 %) eyes were enucleated.Complications after CT included vitreous hemorrhage in 3 (3 %) patients, preretinal hemorrhage in 7 (8 %) cases, subretinal hemorrhage in 2 %, local retinal detachment in 2 %, one (1 %) case of retinal tear, and vitreoretinal traction in 2 (2 %) patients. The mean follow-up time after CT was 44 months (from 4 to 121 months).Conclusion. CT still takes an important place in Rb local treatment, especially in the treatment of small tumors of peripheral localization. However, long-term results have shown that one session of CT is often not enough to achieve complete tumor regression and it requires either repeated use of CT or application of other local methods, mostly transpupillary laser thermotherapy. However, the use of CT is especially relevant in the treatment of small tumors of pre-equatorial localization, which are resistant to thermotherapy, especially in cases of a tumor height more than 1 mm and basal diameter more than 2 mm, which are too large and inconvenient for thermotherapy of peripheral Rb.

Background. 6-mercaptopurine (6-MP) is a drug that is included in the treatment protocols for children and adults with acute lymphoblastic leukemias/lymphomas (ALL/LBL). It is known that individual differences in 6-MP tolerance can be explained by the TPMT and NUDT15 polymorphisms.Aim. To determine 6-MP toxicity profile in adult patients with Ph-negative ALL/LBL treated by ALL-2016 protocol, depending on the TPMT and NUDT15 polymorphisms.Materials and methods. The study included 54 adult patients with Ph-negative ALL/LBL (40 male and 14 female). The median age was 31 (18-51) years. T-ALL/LBL was diagnosed in 29 patients, B-ALL/LBL - in 22, acute leukemia with a mixed immunophenotype - in 3. All patients received treatment according to the multicenter study ALL-2016 (ClinicalTrials.gov, NCT03462095). polymorphisms in NUDT15 (*2, *3) and TPMT (*2, *3A, *3B, *3C) genes were detected using the allele-specific real-time polymerase chain reaction. Genomic DNA was extracted from patients peripheral blood samples. On the induction and consolidation therapy by the protocol, the received and proper 6-MP doses were calculated for all the patients. Drug toxicity was evaluated based on clinical and laboratory data.Results. TPMT and NUDT15 polymorphisms were detected in 11 (20 %) patients, more often in B-ALL - 7 (32 %) of 22 (p <0.05). A lower dose of 6-MP was received by patients with TPMT, NUDT15 polymorphisms only at consolidation IV (p = 0.01). we didn't find a correlation between the 6-MP toxicity and the polymorphisms in our patients (p >0.05).Conclusion. There were no differences in the received dose of 6-MP and the incidence of toxicity in adult patients between Ph-negative ALL/LBL with or without TPMT and NUDT15 polymorphisms treated according to ALL-2016 protocol (p >0.05). further studies including evaluation of 6-MP metabolites concentrations are required for a more complete understanding of the metabolism of this drug.

Introduction. Over the past 5 years, signifi cant progress has been achieved in the treatment of patients with Ph-negative acute lymphoblastic leukemia (ALL). Treatment results were compared between two protocols of the Russian multicenter studies «ALL-2009» and «ALL-2016», in which multicomponent high-dose consolidation was not used. The principle of continuity of treatment was observed with modifi cation of doses of cytostatic drugs depending on the depth of cytopenia. Aim – to compare the 5-year results of two studies and to determine the factors of unfavorable prognosis in the treatment of patients with ALL. Materials and methods. The studies were performed from April 2009 to April 2016 (ALL-2009) and from April 2016 to September 2021 (ALL-2016), and 596 patients were included: 330 in ALL-2009 and 266 in ALL-2016. The analysis was performed in March 2022. The median age of patients in ALL-2009 was 28 years (15–55), in ALL-2016 – 32.5 years (18–55). Cytogenetic studies were performed in 242 patients in ALL-2009 (73.3 %) and 236 patients in ALL-2016 (88.7 %). Patients in the ALL-2016 protocol underwent a centralized assessment of minimal residual disease (MRD) by fl ow cytometry on protocol +70 day (after completion of two induction phases), +133 and +190 days. Transplantation of allogeneic stem hematopoietic cells was performed in 7 % of patients in ALL-2009 and in 9 % in ALL-2016. Results. Overall, relapse-free survival (OS, RFS) and the probability of relapse for a period of 3 years from the moment of inclusion of patients in a particular study were 59 %, 63 % and 23 % for ALL-2009, and for ALL-2016 – 64 %, 59 % and 22 %, respectively. For patients with B-cell precursor ALL, two cytogenetic risk groups were formed, in which long-term survival rates differed signifi cantly: the standard group (hyperploid set of chromosomes and normal karyotype) – OS 63 %, RFS 70 %, and high cytogenetic risk (any abnormal karyotype, except for hyperploidy) – OS 49 %, RFS 52 % (р = 0.001, р = 0.0014). In T-ALL, cytogenetic markers had no prognostic value, but the immunophenotype of early T-cell precursor turned out to be an important predictor of poor prognosis (the probability of relapse was 52 % compared with 15 % for all other immunophenotypic variants). According to the results of centralized monitoring of MRD, it was determined that for B-cell precursor ALL, the signifi cant negative factors are the high cytogenetic risk group and positive MRD status at +70 day, and for T-cells, the early immunophenotype and positive MRD status at +133 day.

Thanks to the treatments that are happening today, the survival rate of patients with retinoblastoma (Rb) has reached 100 %. Despite the positive results of Rb treatment, intraocular complications are observed in observations. Complications that cause visualization of the fundus impede the control of tumor tissue in dynamics, which is associated with enucleation of the eyeball. Despite modern advances in the use of intraocular surgery, a positive and important aspect is the fact that any experience of intraocular infections with a high risk of growth dissemination, which requires an accurate assessment of the state of growth in dynamics and confidence in the stability of remission, which is not always possible with opaque optical environments. In this regard, the question arises of conservative methods of treatment of persistent complications.Given the small age of patients, this makes it difficult to perform conservative treatment in full. Effective are retrobulbar injections, which deliver the drug as close as possible to the posterior pole of the eye. However, for the maximum concentration of the drug, frequent injections are necessary, which is quite traumatic, accompanied by pain, and their frequent implementation contributes to scarring of the retrobulbar tissue. One way to avoid these adverse events is retrobulbar infusion therapy.As a result of retrobulbar infusion therapy, a silicone tube (catheter) is placed in the retrobulbar space for several days, followed by the administration of drugs several times a day.The review contains data on intraocular complications after local treatment of Rb, as well as possible methods for their relief.

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.

This review presents a cosmetic rehabilitation method in children with enucleated eye due to retinoblastoma – primary orbital endoprosthetics. General surgical approaches, implant types, cosmetic outcomes and complications are described within review. Primary orbital endoprosthetics in children with enucleated eye due to retinoblastoma is considered as safe and necessary method of pediatric rehabilitation. Key words: retinoblastoma, primary endoprosthesis replacement of the orbit, implants, chemotherapy, external beam therapy, pediatric rehabilitation.

Brachytherapy (BT) is a method of radiation therapy with radioactive source contacting the tumor. It was proposed by P. Moore and H. Stallard in 1929. Despite those 50 years of experience with the use of BT in ophthalmic oncology, there are only a few studies on the use of Ru-106 BT for retinoblastoma (RB), and no publications on the use of Sr-90 BT have been found. Purpose . To present our own experience with the use of ruthenium and strontium ophthalmic applicators for BT in retinoblastoma. Materials and methods . 120 patients (137 eyes and 194 RB foci) received BT as a local treatment in the period from 2007 to 2020. At the time of treatment the age of the patients varied from 4 to 109 months (mean age 26 months). In 32 % of cases (44 eyes) there were monofocal lesions, and in 68 % of cases (93 eyes) — multifocal. In 36 cases (30 %) BT was performed in the single eye. 79 patients (87 eyes) were treated with the use of ruthenium ophthalmic applicators (OAs), 25 patients (26 eyes) — with the use of strontium OAs, and for the treatment of 16 patients (24 eyes) both ruthenium and strontium OAs were used. Results . Clinically complete tumor regression was achieved in 62 % of cases (120 foci), partial tumor regression — in 31 % of cases (60 foci). In 6 % of cases (12 foci) continuous tumor growth was observed, and tumor recurrence occurred in 1 % of cases (2 foci) within 4 to 6 months after BT. Local tumor control was achieved in 93 % of cases. The single eyes were preserved in 92 % of cases. BT complications of different intensity were reported in 38 % of cases (46 patients — 49 eyes) with the mean follow-up duration of 55 months (3 to 157 months). In 92 % of cases (42 patients — 45 eyes) complications were associated with the use of ruthenium OAs, and only in 8 % of cases (4 patients — 4 eyes) — with the use of strontium OAs. Risk factors for radiation-induced complications were identified: focus size (height more than 2.5 mm [Р = 0.0005], extension more than 7.3 mm [Р < 0,0001]), sclera dose more than 626 Gr (Р = 0,0002), and the central localization of the tumor (Р < 0.0001). Conclusions . Ruthenium-106 and strontium-90 brachytherapy is a highly effective treatment modality for the management of RB.

External beam radiotherapy (EBR) remained for a long time the only method of treatment in children with recurrent and resistant retinoblastoma (RB). This method often leads to serious complications, including the occurrence of secondary malignant tumors. Currently, EBR is used as second-line (salvage) therapy. There is no data in the literature of using Gamma Knife stereotactic radiosurgery (GKRS) in RB treatment. Purpose. To present 5-year experience of using GKRS in patients with RB. Material and methods. 16 children (17 eyes) were treated using GKRS in the period from 2015 to 2019. Mean patient age was 34.7 months (range, 12–114 months). The eyes were classified as group B (n=4), C (n=1), D (n=12). 3 children had the last eye. All patients received systemic and local chemotherapy, all types of local treatment modalities before using GKRS. Recurrent and resistant RB was the indication for GKRS. Marginal 50% mean dose was 22 Gу (range, 20–24 Gу), depending on tumour type and location. Radiation doses were evaluated accounting critical eye structures and the orbit bones. Results. Complete regression was achieved in 11 patients, partial in 2. Four patients underwent enucleation after GKRS. Indications for enucleation were retinoblastoma recurrence (n=2) and vitreous hemorrhage with total retinal detachment (n=2). 13 eyes were salvaged with no signs of keratopathy, uveitis or damage of orbital and surrounding tissues during mean follow-up 30.6 months (range, 7–60 months). Сomplications of different severity occurred in 13 patients, including vitreous hemorrhage in 6 patients, which was successfully treated both conservative (n=3) and using pars plana vitrectomy with simultaneous melphalan irrigation (n=3). Conclusion. The first experience of GKRS as an alternative to enucleation in patients with RB was proved to be reasonable and successful. Key words: retinoblastoma, gamma-knife, stereotactic radiosurgery.

Introduction. Retinoblastoma (RB) is a malignant tumor of the retina, the survival rate for the intraocular form reaches 99 %. According to the researchers, the risk factors for the occurrence of refractory or recurrent forms of RB are the size of the tumor at primary diagnosis (more than 15 mm), the child's age at the onset of the disease (up to one year), bilateral RB, and the presence of subretinal and vitreal screenings. If methods of local destruction of the tumor are not applicable for the successful treatment of intraocular refractory or recurrent RB, then they resort to the second line of polychemotherapy as an alternative to enucleation. New versions of local chemotherapy and radiation therapy (gamma knife) are being developed and applied. Nowadays, researchers have a negative attitude towards traditional radiation therapy (EBRT) as a method of organ-preserving treatment due to serious consequences (asymmetry of the facial skeleton and second radio-induced tumors).Aim of the study — to increase the effectiveness of organ-preserving treatment in patients with refractory or recurrent intraocular RB.Materials and methods. In the period from 10.2018 to 12.2019 at the N.N. Blokhin National Medical Research Centre of Oncology it was received three-component selective intra-arterial chemotherapy (SIAC) in 15 patients (15 eyes) aged 11 to 52 months. Eyes initially affected by RB (n = 15), according to the IIRC (Murphree) classification, had the following groups: group B in 1 case, group C in 3, group D in 7, and group E in 4 eyes. It should be noted that all patients initially received intensive combined conservative therapy: in 11 (73 %) of 15 cases — systemic chemotherapy VEC; in 13 (86 %) of 15 — SIAC with melphalan, in all cases, additionally, two-component SIAC was used in combination with melphalan with topotecan. In some cases, local therapy in the form of intravitreal chemotherapy (IVIC) was added to the treatment of 6 (40 %) of 15 patients in the form of melphalan monotherapy and in one case (6 %) a doublet was used in combination with melphalan and topotecan. Also, in some patients, additional local ophthalmic therapy was used: transpupillary thermotherapy (TTT) in 6 out of 15 patients, including in combination with cryotherapy (CT) in 1 patient and in combination with brachytherapy (BT) in one case. At the same time, incomplete tumor regression (refractory form of the disease) was noted in 7 out of 15, and a recurrent course of the disease — in 8 out of 15 patients. Incomplete tumor regression and recurrent RB were the reasons for the appointment of a three-component SIAC using carboplatin, melphalan and topotecan, in combination with IVIC with pronounced endophytic growth of RB, as an alternative to irradiation and enucleation of the eye.Results. The average number of three-component SIAC courses was 1.46 ± 0.63 (rang 1—3). The combination of SIAHT with IVHT was performed in 3 out of 15 patients. All children (n = 15) are alive with a median period of follow-up of23.92 ± 15.68 (10—64) months. One in 15 patients was lost from observation due to their parents’ desire to be treated abroad. It is known that the child is alive, but there is no data on the condition of his eyes. 9 out of 14 patients needed additional treatment after SIAC intensification. To consolidate the resulting effect as a full regression in 2 cases, the final IVIC courses were conducted (n = 2). In connection with the presence of residual tumor and/or intraocular progression and/or appearance of new lesions in 1 of 9 patients were IVIC and TTT, 2 of 9 — IVIC, SIAC, CT, TTT. In 4 out of 9 cases, enucleation was performed, and in 2 out of 4 — the operation was performed after continuing the attempt of organ-preserving treatment: after CT and TTT (n = 1) and IVIC, CT, TTT and BT (n = 1). No child was given ERBT. There were no cases of stroke after SIAC. We managed to save 10 (71.4 %) of 14 eyes with visual acuity: object vision in 4 (40 %) out of 10, eye fixation in 3 (30 %) out of 10, and light perception in 3 (30 %) out of 10 cases. The average follow-up period from the end of three-component SIAC in 14 patients was 13.57 ± 5.27 (6—22) months.Conclusion. Thus, the three-component SIAC is effective and safe for patients with refractory and recurrent retinoblastoma, as evidenced by a high percentage of retained eyes and the presence of visual functions from light perception to object vision.

Purpose. To evaluate the spectrum and the occurrence frequency of lesions simulating retinoblastoma in different age groups. Material and methods. A retrospective study of 608 patients (871 eyes) with suspected retinoblastoma was performed in the Ocular Oncology and Radiology Department of the Fyodorov Eye Microsurgery Federal State Institution in the period from 2007 to 2020. The mean patient age at presentation was 21 months (from 1 to 209 months). In 475 patients (78.1%) (715 eyes), the diagnosis of retinoblastoma was confirmed after a comprehensive assessment of the eye. 133 patients (156 eyes) (21.9%) had symptoms mimicking retinoblastoma-pseudoretinoblastomas. All patients with pseudoretinoblastomas were divided into different groups based on the simulating condition and age: from 0 to 1 year, from 1 to 2 years, from 2 to 5 years, older than 5 years. Results. There were 25 conditions simulating retinoblastoma. The most common conditions were Coats' disease (n=17; 12.8%), combined hamartoma of retina and retinal pigment epithelium (n=12. 9%), retinal detachment (n=11; 8.3%), vitreous opacities caused by intrauterine uveitis (n=11; 8.3%), choroidal hemangioma (n=11; 8.3%), vasoproliferative tumor (n=10; 7.5%), retinopathy of prematurity (n=7; 5.3%), morning glory syndrome (n=7; 5.3%). Most patients had unilateral lesions (n=116; 87.2%). Pseudoretinoblastomas differed based on age at presentation, because children 1 year of age or younger were most likely to have vitreous opacities caused by intrauterine uveitis (n=9; 21.4%) and retinopathy of prematurity (n=7; 16.7%); children aged from 1 to 2 years – Coats' disease (n=4; 20%) and choroidal hemangioma (n=3; 15%), from 2 to 5 years – Coats' disease (n=8; 21.6%), older than 5 years – Coats' disease (n=5; 14.7%) and vasoproliferative tumors (n=7; 20.6%). Conclusion. Timely referral of children with suspected retinoblastoma in specialized ocular oncology centers helps to avoid unnecessary treatment for retinoblastoma, enucleation and improve the vital prognosis.

Данный обзор литературы посвящен проблеме брахитерапии у больных ретинобластомой и включает обобщенные данные об истории развития метода и его эффективности, технике операции, видах офтальмоаппликаторов и радиоизотопов, рекомендуемых дозах облучения и возможных осложнениях. Особое внимание в данной статье уделено изотопам рутения (Ru-106) и стронция (Sr-90) ввиду их использования на территории Российской Федерации. Для формирования обзора были использованы отечественные и зарубежные источники литературы, опубликованные в период с 1931 г. по настоящее время.

Introduction. Among main curative substances in acute lymphoblastic leukaemia/lymphoma (ALL/LBL) is 6-mercaptopurine (6-MP). However, the severity of adverse reactions (ADRs) to this drug varies considerably among patients, which is sometimes conditioned by individual single nucleotide polymorphisms in key 6-MP metabolism enzyme genes. Aim - a literature review on the role of TPMT and NUDT15 gene variants in 6-MP metabolism in ALL/LBL. Main findings. The TPMT and NUDT15 genes encode enzymes mediating key steps of the 6-MP metabolism. The metabolites determine the 6-MP therapeutic and toxic properties, with ADRs emerging when their concentrations alter. A number of TPMT and NUDT15 single nucleotide polymorphisms are associated with varied activities of the encoded enzymes, and their allelic combinations condition functional and non-functional phenotypes. Non-functional variant carriers more likely develop toxicity on 6-MP treatment compared to functional phenotypes. Non-functional TPMT/NUDT15 carriers should have the 6-MP dosage reduced to minimise emerging ADRs.

Brachytherapy (BT) is a method of radiation therapy with radioactive source contacting the tumor. It was proposed by P. Moore and H. Stallard in 1929. Despite those 50 years of experience with the use of BT in ophthalmic oncology, there are only a few studies on the use of Ru-106 BT for retinoblastoma (RB), and no publications on the use of Sr-90 BT have been found.Purpose. To present our own experience with the use of ruthenium and strontium ophthalmic applicators for BT in retinoblastoma.Materials and methods. 120 patients (137 eyes and 194 RB foci) received BT as a local treatment in the period from 2007 to 2020. At the time of treatment the age of the patients varied from 4 to 109 months (mean age 26 months). In 32% of cases (44 eyes) there were monofocal lesions, and in 68% of cases (93 eyes) — multifocal. In 36 cases (30%) BT was performed in the single eye. 79 patients (87 eyes) were treated with the use of ruthenium ophthalmic applicators (OAs), 25 patients (26 eyes) — with the use of strontium OAs, and for the treatment of 16 patients (24 eyes) both ruthenium and strontium OAs were used.Results. Clinically complete tumor regression was achieved in 62 % of cases (120 foci), partial tumor regression — in 31% of cases (60 foci). In 6% of cases (12 foci) continuous tumor growth was observed, and tumor recurrence occurred in 1% of cases (2 foci) within 4 to 6 months after BT. Local tumor control was achieved in 93% of cases.The single eyes were preserved in 92% of cases. BT complications of different intensity were reported in 38% of cases (46 patients — 49 eyes) with the mean follow-up duration of 55 months (3 to 157 months). In 92 % of cases (42 patients — 45 eyes) complications were associated with the use of ruthenium OAs, and only in 8% of cases (4 patients — 4 eyes) — with the use of strontium OAs. Risk factors for radiation-induced complications were identified: focus size (height more than 2.5 mm [P =0.0005], extension more than 7.3 mm [P <0,0001]), sclera dose more than 626 Gr (P = 0,0002), and the central localization of the tumor (P <0.0001).Conclusions. Ruthenium-106 and strontium-90 brachytherapy is a highly effective treatment modality for the management of RB.

Purpose. To present results of cataract surgery in children with retinoblastoma. Material and methods. Within the period from 2012 to 2020, cataract surgery was performed in 21 children (22 eyes) with retinoblastoma aged 28 to 155 months (average – 65 months). Tumors of group B occurred in 2 cases, group C – in 4, group D – in 14, group E – in 1. In 8 cases, cataract occurred in a single eye. Posterior capsular cataract was observed in 18 patients, total – in 3. In all cases, the presence of cataract impeded the control of the tumor. Before cataract surgery all children underwent systemic chemotherapy, some of them also underwent intra-arterial and/or intravitreal chemotherapy, external beam radiotherapy, Gamma Knife stereotactic radiosurgery and local treatment modalities (episcleral plaque brachytherapy, thermotherapy, cryotherapy). There were no signs of tumor progression in all cases at the time of cataract surgery. The mean interval between complete tumor regression and cataract surgery was 23 months (range 6–75 months). Results. Full transparency of optical media was achieved in all eyes after surgery. No intraoperative and postoperative complications occurred. The final visual acuity was improved in 12 eyes, in the rest visual acuity could not be determined due to age. There were no signs of tumor recurrence or metastases in mean follow-up after surgery of 29 months (range 3–60). Conclusion. Our experience of cataract surgery in children with complete regression of retinoblastoma was proved to be a safe and effective way to improve visual functions and achieve transparency of optical media. Key words: retinoblastoma, cataract surgery, ophtalmooncology, functional results