We compared the efficacy and safety of eltrombopag (ELTR) combined with immunosuppressive therapy (IST) and IST alone in treatment-naïve children with severe (SAA) and very severe (vSAA) aplastic anemia. Ninety-eight pediatric patients were randomized to receive horse antithymocyte globulin and cyclosporin A with (n=49) or without (n=49) ELTR. The primary endpoint was the overall response rate (ORR) at 4 months. After 4 months, nonresponders were crossed over to the alternative group. In all patients, the ORR in ELTR+IST and IST groups was similar (65% vs. 53%, p=0.218); however, the complete response (CR) rate was significantly higher in ELTR+IST group (31% vs. 12%, p=0.027). In severity subgroups, the ORR was 89% vs. 57% (p=0.028) in favor of IST+ELTR in SAA, but it did not differ in patients with vSAA (52% vs. 50%, p=0.902). At 6 months after the crossover, 61% of initial ELTR(-) patients achieved a response compared to 17% of initial ELTR(+) patients (p=0.016). No significant difference in ELTR+IST and IST groups was observed in the 3-year OS (89% vs. 91%, p=0.673) or the 3-year EFS (53% vs. 41%, p=0.326). There was no unexpected toxicity related to ELTR. Adding ELTR to standard IST was well tolerated and increased the CR rate. The greatest benefit from ELTR combined with IST was observed in patients with SAA, but not in those with vSAA. The second course of IST resulted in a high ORR in initial ELTR(-) patients who added ELTR and had limited efficacy among patients who received ELTR upfront. Clinicaltrials.gov #NCT03413306.

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Background. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment method of refractory and recurrent forms of acute leukemia in children, while the question of choosing a conditioning regimen in order to achieve the best treatment results remains debatable. Conditioning based on total body irradiation (TbI) was confirmed to be most effective in some trials, but there are still issues of overcoming early and late toxicity, as well   as difficulties in planning and routing patients.Aim. To share the experience of interdisciplinary patient management during the conditioning period with TbI inclusion in Saint petersburg, to evaluate the feasibility, toxicity and effectiveness of the method.Materials and methods. patients undergoing allo-HSCT for high risk acute lymphoblastic leukemia conditioned either with TbI (n = 12) or chemotherapy (n = 10) were included. Medical data were retrospectively analyzed with an assessment of the following transplant outcomes: HSCT-associated toxicity, the frequency and severity of infectious complications, graft versus host disease, as well as overall and event-free survival rates. we have evaluated radiotherapy plans in order to assess the compliance of radiation exposure with acceptable values for critical organs.Results. All patients with acute lymphoblastic leukemia in both groups received appropriate myeloablative conditioning. According to the study results, despite the lack of significance, we obtained differences in HSCT-associated mortality (8.3 and 30 %; p = 0.151), 2-years overall and event-free survival (66 ± 13.6 and 36 ± 16.1 %; p = 0.122) in group with TbI and HdCT respectively. It should be noted that there was a trend towards a decrease of toxic reactions frequency in case of TbI-containing regimens; however we didn’t reveal any significant differences in the number of infectious complications during post-transplant period. The median follow-up was 24.2 months and there were no signs of delayed toxicity.Conclusion. TbI-based conditioning was well tolerated with a low incidence of early and delayed toxicity, better overall and event-free survival. based on feasibility of TbI in Saint petersburg hospitals it is possible to recommend the method in routine practice, taking into account clinical indications.

Medulloblastoma (MB) is the most common pediatric brain tumor which accounts for about 20% of all pediatric brain tumors and 63% of intracranial embryonal tumors. MB is considered to arise from precursor cell populations present during an early brain development. Most cases (~70%) of MB occur at the age of 1–4 and 5–9, but are also infrequently found in adults. Total annual frequency of pediatric tumors is about 5 cases per 1 million children. WNT-subtype of MB is characterized by a high probability of remission, with a long-term survival rate of about 90%. However, in some rare cases there may be increased metastatic activity, which dramatically reduces the likelihood of a favorable outcome. Here we report two cases of MB with a histological pattern consistent with desmoplastic/nodular (DP) and classic MB, and genetically classified as WNT-MB. Both cases showed putative causal somatic protein truncating mutations identified in microtubule-associated genes: ARID2, TUBB4A, and ANK3.

Brucellosis is highly contagious zoonotic bacterial disease caused by gram-negative genus. It has a wide spectrum of clinical manifestations and due to variety and nonspecificity of clinical signs the diagnostics can be very complicated. We present a clinical case of severe chronic brucellosis in a 5-years old boy with long-term course of disease and multiorgan involvement. A different complication of brucellosis including severe syndrome of inappropriate ADH secretion (SIADH) are discussed. Despite severe course of disease patient achieved significant clinical improvement due to multidisciplinary approach and optimal etiotropic and pathogenetic treatment.