Treatment results of pediatric acute myeloid leukemia with epigenetic drugs addition

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 %)

Изменения в серотиповом составе Streptococcus pneumoniae, циркулирующих среди детей в Российской Федерации, после внедрения 13-валентной пневмококковой конъюгированной вакцины

During a prospective multicenter non-interventional observational study, a comparative assessment was made of the serotype structure of pneumococci circulating among healthy children under the age of 5 years and children of the same age group with signs of respiratory infections in the periods 2016-2018 and 2020-2022. Data on the serotype structure of pneumococci in the period from 2016-2018 were obtained from our previous works. In 2020-2022 the study included 2066 healthy children and 603 children with respiratory infections. Streptococcus pneumoniae and their DNA were detected in nasopharyngeal swabs by classical culture and molecular methods. Typing was carried out by molecular methods. On the territory of the Russian Federation, pneumococci belonging to the serotypes included in the 13-valent vaccine are being forced out of circulation and replaced by non-vaccine serotypes. Before the introduction of mass antipneumococcal vaccination (until 2015), the 13-valent conjugate vaccine covered from 66.2% to 92% of pneumococci, after the start of mass anti-pneumococcal vaccination in the period 2016-2018, coverage decreased to 57.3%. Between 2020 and 2022, coverage was less than 40%. The main “non-vaccine” serotypes/serogroups circulating in the Russian Federation are 15AF, 11AD, 23A, 9LN and 16F.В ходе проспективного многоцентрового не интервенционного обсервационного исследования была проведена сравнительная оценка серотиповой структуры пневмококков, циркулирующих среди здоровых детей в возрасте до 5 лет и детей этой же возрастной группы с признаками респираторных инфекций в периоды 2016–2018 гг. и 2020–2022 гг. Данные о серотиповой структуры пневмококков в период 2016–2018 гг. были получены из наших предыдущих работ. В 2020–2022 гг. в исследование было включено 2066 здоровых детей и 603 ребенка с респираторными инфекциями. Streptococcus pneumoniae и их ДНК детектировали в назофарингеальных мазках классическими культуральными и молекулярными методами. Типирование проводили молекулярными методами. На территории Российской Федерации происходят процесс вытеснения из циркуляции пневмококков, относящихся к серотипам, входящим в 13-валентную вакцину, и их замещение невакцинными серотипами. Перед внедрением массовой антипневмококковой вакцинации (до 2015 г.) конъюгированная 13-валентная вакцина обеспечивала на тот момент охват от 66,2% до 92% пневмококков, после начала массовой антипневмококковой вакцинации в период 2016–2018 гг. охват снизился до 57,3%. В период с 2020 по 2022 г. охват составил менее 40%. К основным «невакцинным» серотипам/серогруппам, циркулирующим на территории Российской Федерации, относятся 15AF, 11AD, 23A, 9LN, 16F