In Memory of Professor A.Yu. Zaritskey

16 октября 2021 г. после продолжительной болезни скончался Андрей Юрьевич Зарицкий, один из ведущих ученых России в области гематологии, выдающийся клиницист, доктор медицинских наук, профессор, директор института онкологии и гематологии Национального медицинского исследовательского центра им. В.А. Алмазова.

Андрей Юрьевич Зарицкий родился 11 марта 1950 г. в Ленинграде. В 1973 г. окончил Первый Ленинградский медицинский институт им. акад. И.П. Павлова.

Его профессиональный путь начался на кафедре внутренних болезней этого же института, где он успешно закончил обучение по специальности «Гематология» в 1975 г. в ординатуре и 1978 г. в аспирантуре. Будучи одним из любимых учеников академика РАМН Владимира Андреевича Алмазова, Андрей Юрьевич под его руководством занимался прорывными для своего времени исследованиями микроокружения лейкозных клеток. В аспирантуре он работал над темой «Колониеобразующая способность костного мозга, колониестимулирующая активность лейкоцитов периферической крови и плазмы у гематологически здоровых лиц и больных хроническими лимфопролиферативными заболеваниями». В 1979 г. Андрей Юрьевич Зарицкий успешно защищает диссертацию по данной теме и становится кандидатом медицинских наук. Продолжая изучать биологию лейкозных клеток и их микроокружения, в 1996 г. он заканчивает работу над докторской диссертацией по теме: «Исследование фибробластных клеток костного мозга у больных с заболеваниями системы крови». В 2001 г. ему присвоено ученое звание профессора.

Андрей Юрьевич Зарицкий посвятил гематологии всю свою жизнь, активно занимался научной, лечебной и преподавательской деятельностью в избранной им области. В течение многих лет он был научным руководителем отделения гематологии Городской больницы № 31 г  Санкт-Петербурга, был профессором кафедры факультетской терапии Первого Санкт-Петербургского медицинского университета им. акад. И.П. Павлова. В 2008 г. Андрей Юрьевич организовал гематологическую службу в ФГБУ «НМИЦ им. В.А. Алмазова» Минздрава РФ и возглавил Институт гематологии НМИЦ. В институте проводились и проводятся работы в области фундаментальных, прикладных и трансляционных исследований злокачественных опухолей системы крови.

В Институте гематологии, в настоящее время переименованном в Институт онкологии и гематологии ФГБУ «НМИЦ им. В.А. Алмазова», под руководством проф. А.Ю. Зарицкого появились и успешно развивались научные и практические сферы гематологии. Созданы новые клинические отделения онкогематологии для детей и взрослых, где были внедрены инновационные методы химио- и иммунотерапии онкогематологических заболеваний, а также современные методы диагностики и мониторинга результатов терапии.

Андрей Юрьевич Зарицкий свободно владел английским языком, активно развивал международное сотрудничество с зарубежными коллегами. Он был активным членом рабочей группы по хроническому миелолейкозу и хроническому лимфолейкозу Европейской сети по изучению лейкозов (European LeukemiaNet), был экспертом международного уровня, соавтором рекомендаций European LeukemiaNet 2020 г. по лечению хронического миелоидного лейкоза. Благодаря его организаторским способностям и известности как ученого ему было предложено участие в нескольких международных широкомасштабных исследовательских проектах European LeukemiaNet, а также в научной работе, проводившейся Международным консорциумом в рамках 7-рамочной программы ЕС (SystemAge, WorkPackage 4).

Он принимал активное участие в развитии молекулярной диагностики и мониторинга результатов терапии хронического миелолейкоза в России, в т. ч. в организации международной стандартизации методики количественного определения гена BCR-ABL. Андрей Юрьевич Зарицкий был избран Послом в России крупнейшего онкологического центра США MD Anderson Cancer Centre, был представителем International Chronic Myeloid Leukemia Foundation (Международного фонда по ХМЛ) в России. В рамках программы клинического наставничества фонда iCMLf Андрей Юрьевич делился опытом и знаниями с коллегами из стран СНГ. Он был приглашенным спикером на многих международных конференциях, проводимых не только в России, но и в Украине, Республике Беларусь, Узбекистане, Казахстане.

Проф. А.Ю. Зарицкий вел регулярную просветительскую работу в рамках семинаров, региональных и всероссийских конференций, делился своими научными и клиническими знаниями с коллегами из разных регионов России.

Андрей Юрьевич также вел просветительскую деятельность среди пациентов, проводил школы в рамках программы «Право жить» и при поддержке Всероссийского общества онкогематологии «Содействие», был главным исследователем более чем в 40 клинических исследованиях инновационных лекарственных препаратов для лечения пациентов онкогематологического профиля.

Профессор Андрей Юрьевич Зарицкий был членом редакционной коллегии журналов «Трансляционная медицина», «Вестник гематологии».

За долгие годы работы он воспитал плеяду учеников, которые продолжают лечебную, исследовательскую и педагогическую работу как в НМИЦ им. В.А. Алмазова, так и в ведущих гематологических центрах нашей страны и мира. На его счету более 360 научных публикаций, несколько монографий и патентов. За заслуги в области здравоохранения Андрей Юрьевич Зарицкий награжден нагрудным знаком «Отличник здравоохранения».

Андрей Юрьевич поражал и заражал своей неисчерпаемой энергией, был человеком пытливого и проницательного ума, обширной эрудиции и колоссального трудолюбия. Он был искренним и открытым человеком, при этом очень принципиальным и требовательным как к себе, так и к своим ученикам и коллегам. Умел находить единомышленников, быть настоящим другом. Таким его помнят многочисленные коллеги и друзья.


Из воспоминаний коллег

I first met Professor Andrey Zaritskey during last year of medical school, he was assigned as our teacher in Hematology course. I owe him my choice of Hematology as my future specialty. At that time, we had very limited options for therapy of acute leukemia patients, with limited supportive care options, and I saw how difficult and acutely ill patients with hematologic malignancies are. AYu told me at that time: “These are very sick patients. Someone must treat these patients. And I think this should be you”. With those words, I continue to treat leukemia patients now at MD Anderson Cancer Center, for more than 25 years in my career. AYu was mentoring me in my laboratory research when I started my work at hematology hospital and later in clinic. He had unrelenting passion in science and always asked “out-of-the box” questions that could lead to discoveries. I inherited for life his enthusiasm and curiosity in laboratory and clinical research, that shaped my career, leading me to what I am now, physician-scientist. Professor Zaritskey was that rare hybrid of excellent clinician, thoughtful and forward-looking researcher, outstanding mentor and a wonderful human being. He has helped in many ways his multiple trainees, their relatives and friends, and was highly respected and loved by his colleagues and mentees. Professor Zaritskey was highly regarded nationally and internationally for his efforts in treatment of CML patients in Russia. He was integral part of multiple hematology schools disseminating the knowledge of CML therapy across multiple regions of the country. Dr. Zaritskey attended ASH and other international meetings, visited several times MD Anderson and became an ambassador at SOHO hematology meeting. AYu worked till the very last minute. Even being very ill confined to the hospital bed, he continued consulting responsibilities on his clinical unit, guided laboratory research and chaired international virtual conference. His dedication, passion to science and hematology and his nature of a human being with big heart will be always inspiring me in my life and professional career.

Marina Konopleva, MD, PhD, Professor, Member of the clinical faculty in the Departments of Leukemia and Stem Cell Transplantation of the MD Anderson Cancer Center (Houston, USA)

Я впервые встретила профессора Андрея Юрьевича Зарицкого на последнем курсе медицинского факультета, он был назначен нашим преподавателем гематологии. Именно благодаря ему я выбрала гематологию своей будущей специальностью. В то время у нас были очень ограниченные возможности лечения пациентов с острыми лейкозами, ограниченные варианты поддерживающей терапии, и я видела, насколько тяжелыми бывают пациенты с онкогематологическими заболеваниями. Андрей Юрьевич сказал мне тогда: «Эти пациенты очень больны. Кто-то должен их лечить. И я думаю, что это должны быть Вы». С этими словами я продолжаю лечить пациентов с лейкозом в онкологическом центре им. М.Д. Андерсона (MD Anderson Cancer Center) на протяжении всей своей карьеры, более 25 лет. Андрей Юрьевич был моим наставником в лабораторных исследованиях, когда я начинала работать в гематологической больнице, а затем — в клинике. Он обладал неослабевающей страстью к науке и всегда задавал нестандартные вопросы, которые могли привести к открытиям. Я на всю жизнь унаследовала его энтузиазм и жажду знаний в лабораторных и клинических исследованиях, которые определили мою карьеру и позволили мне стать тем, кем я сейчас являюсь, — врачом-ученым. Профессор Зарицкий сочетал в себе качества прекрасного клинициста, вдумчивого и прогрессивного исследователя, выдающегося наставника и замечательного человека, что встречается так редко. Он во многом помогал своим многочисленным ученикам, их родственникам и друзьям, его очень уважали и любили коллеги и подопечные. Профессор Зарицкий пользовался большим уважением на национальном и международном уровнях за приложенные усилия в области лечения пациентов с хроническим миелоидным лейкозом (ХМЛ) в России. Он был неотъемлемой частью нескольких гематологических школ, обеспечив распространение знаний о терапии ХМЛ во многих регионах страны. Доктор Зарицкий участвовал в конференциях ASH и других международных встречах, несколько раз посетил онкологический центр им. М.Д. Андерсона и стал послом на гематологической конференции SOHO. Андрей Юрьевич работал до последней минуты. Даже будучи очень больным и прикованным к больничной койке, он продолжал консультировать свое клиническое отделение, руководил лабораторными исследованиями и был председателем на Международной виртуальной конференции. Его преданность делу, страсть к науке и гематологии и качества человека с большим сердцем всегда будут вдохновлять меня в моей жизни и профессиональной карьере.

Марина Юрьевна Коноплева, д-р мед. наук, профессор, член клинического факультета отделения лейкоза и трансплантации стволовых клеток онкологического центра им. М.Д. Андерсона (Хьюстон, США)


European LeukemiaNet

Coordinator:

Prof. Dr. Dr. h. c. R. Hehlmann

ELN Foundation

Im Langgewann 45

69469 Weinheim

E-mail: hehlmann.eln@gmail.com

Date: 29.01.2022

The hematologic community lost a leader and international communicator, I lost a friend. Professor Dr. Andrey Zaritskey died in St. Petersburg after fighting a malicious disease for 4 years.

I met Andrey Zaritskey around 2005 when he on behalf of Paul’s University and the Almazov National Research Center joined the European LeukemiaNet (ELN) highlighting his comprehensive research interests and his cooperative spirit. Upon his invitation, I visited St. Petersburg in September 2006 starting 15 years of fruitful cooperation in the field of leukemia, particularly chronic myeloid leukemia (CML).

Promoting international cooperation, Andrey Zaritskey organized participation of young coworkers in international training and research activities around the world such as Dmitry Motorin in Bologna, Marina Konopleva in Houston and others, including attending the Annual ELN Symposia in Heidelberg and Mannheim/Germany and the Annual Workshops of the European Investigators on CML (EI-CML) across Europe. With Anthony Ho from Heidelberg University he embarked on an official Russian-German cooperation project on stem cells, and with Hagop Kantarjian and Elias Jabbour from MD Anderson Cancer Center (MDACC) in Houston on a Russian-American cooperation on clinical CML research. With the help of Natalya Lazorko of his team, he succeeded hosting in St. Petersburg an EI-CML Workshop in 2013, and an international workshop in cooperation with MDACC and ELN in 2017.

For promoting European integration of research in the field of leukemia Andrey Zaritskey was awarded the ELN Merit Award 2010. He was invited by ELN to join the international panel of experts to help develop the ELN recommendations for treating CML published in “Leukemia” in 2020.

An important aspect of Andrey Zaritskey’s promotional activity was familiarizing international cooperators with the scientific landscape and cultural heritage of St. Petersburg and Russia. Because of his scientific standing and outgoing, but always modest, personality he was well respected and invited to lectures and seminars all over Russia. By taking me along to some of these events he made me feel at home in Russia thereby deepening the spirit of cooperation.

Since 2008, Andrey Zaritskey established as director the new Institute of Hematology at the Almazov National Medical Research Center with research facilities and a transplantation unit. During the 13 years of his directorship he developed the institute into a well working institution with a dedicated, future-oriented team of young doctors and researchers and with international visibility.

The institute is well prepared for continuing top-level research and patient care in international cooperation under his successor, his long-term associate Professor Elza Lomaia.

Профессор Рудигер Хельманн, координатор Европейской сети по изучению лейкозов


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Pharmacoeconomic Analysis of CAR-T Cell Therapy in Diffuse Large B-Cell Lymphoma and B-Lineage Acute Lymphoblastic Leukemias

IV Gribkova, AA Zavyalov

Research Institute of Healthcare and Medical Management, 9 Sharikopodshipnikovskaya ul., Moscow, Russian Federation, 115088

For correspondence: Irina Vladimirovna Gribkova, PhD in Biology, 9 Sharikopodshipnikovskaya ul., Moscow, Russian Federation, 115088; Tel.: +7(916)078-73-90; e-mail: igribkova@yandex.ru

For citation: Gribkova IV, Zavyalov AA. Pharmacoeconomic Analysis of CAR-T Cell Therapy in Diffuse Large B-Cell Lymphoma and B-Lineage Acute Lymphoblastic Leukemias. Clinical oncohematology. 2022;15(2):205–12. (In Russ).

DOI: 10.21320/2500-2139-2022-15-2-205-212


ABSTRACT

Genetically modified Т-lymphocytes with chimeric antigen receptors (CAR-T cells) represent a new treatment strategy in relapsed/refractory B-cell malignant neoplasms. In 2017–2018 two CAR-T cell drugs, tisagenlecleucel and axicabtagene ciloleucel, were approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for clinical use in patients with refractory acute lymphoblastic leukemia and relapsed/refractory B-cell lymphomas. Due to its high efficacy, CAR-T cell therapy is increasingly becoming an integral part of clinical practice. However, this method of chemotherapy is very expensive. The mean cost of tisagenlecleucel is $475,000 and that of axicabtagene ciloleucel is $373,000. It is worth noting that these are only the drug prices which exclude other therapy-related costs. In the studies of 2018–2020 groups of researchers attempted to estimate the CAR-T cell therapy-associated costs. The aim of the present review is to analyze these studies and to assess the total treatment cost and expense structure, as well as to discuss the factors underlying the increasing costs and to explore opportunities to improve availability of the CAR-T technology, on the whole. The results showed that the mean cost of tisagenlecleucel therapy in B-cell lymphoma was $515,150 and that of axicabtagene ciloleucel therapy was $503,955. The treatment cost in acute lymphoblastic leukemia was $580,459. The major factors affecting the total therapy cost were CAR-T cell drug prices, severity of adverse events, and high tumor load prior to CAR-T cell drug infusion. It is agreed that the main opportunities to rise affordability of the CAR-T cell therapy lie in reducing the drug prices (for example, by means of medical facility-based production at its own expense), further therapy improvement aimed at less toxicity, and its implementation at earlier stages of tumor disease.

Keywords: B-cell lymphoma, acute lymphoblastic leukemia, CAR-T cell therapy, chimeric antigen receptor, tisagenlecleucel, axicabtagene ciloleucel, costs, review.

Received: October 29, 2021

Accepted: February 15, 2022

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Статистика Plumx английский

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Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Myelodysplastic Syndromes with Trisomy 8 and/or Monosomy 7

MV Latypova, NN Mamaev, TL Gindina, AI Shakirova, OV Paina, AA Osipova, TV Rudakova, EV Morozova, SN Bondarenko, LS Zubarovskaya

RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo ul., Saint Petersburg, Russian Federation, 197022

For correspondence: Prof. Nikolai Nikolaevich Mamaev, MD, PhD, 6/8 L’va Tolstogo ul., Saint Petersburg, Russian Federation, 197022; e-mail: nikmamaev524@gmail.com

For citation: Latypova MV, Mamaev NN, Gindina TL, et al. Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Myelodysplastic Syndromes with Trisomy 8 and/or Monosomy 7. Clinical oncohematology. 2022;15(2):198–204. (In Russ).

DOI: 10.21320/2500-2139-2022-15-2-198-204


ABSTRACT

The study assessed the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 34 patients with cytogenetically verified variants of myelodysplastic syndrome (MDS) with trisomy 8 and/or monosomy 7, who were treated at the RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation from 2013 to 2020. Both adult and pediatric MDS were analyzed without excluding the variants with two additional chromosomal abnormalities or complex karyotype. The study revealed that а) allo-HSCT should be performed in the treatment of both MDS variants; b) the outcomes of trisomy 8 treatment appeared to be better; c) children with monosomy 7 showed a higher rate of toxic complications in allo-HSCT.

Keywords: myelodysplastic syndromes, cytogenetic variants, trisomy 8, monosomy 7, allo-HSCT.

Received: October 2, 2021

Accepted: March 6, 2022

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Статистика Plumx английский

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Current Quality-of-Life Aspects in Patients with Classical Ph-Negative Myeloproliferative Neoplasms in the Russian Federation: Results and Discussion of the National Observational Program MPN-QoL-2020

TI Ionova1,2,3,*, EA Andreevskaya4,*, EN Babich5,*, NB Bulieva6,7,*, OYu Vinogradova8,9,10,*, EM Volodicheva11,*, SV Voloshin12,13,14,*, NN Glonina15,*, SK Dubov16,*, NB Esef’eva17,*, AYu Zaritskey18,*, EE Zinina19,*, MO Ivanova20,*, TYu Klitochenko21,*, AV Kopylova22,*, AD Kulagin23,*, GB Kuchma24,25,*, OYu Li26,*, EG Lomaia18,*, AL Melikyan27,*, VYa Melnichenko3,*, SN Menshakova28,*, NV Minaeva29,*, TA Mitina30,*, EV Morozova23,*,TP Nikitina1,2,*, OE Ochirova31,*, AS Polyakov13,*, TI Pospelova32,*, AV Proidakov33,*, OA Rukavitsyn34,*, GSh Safuanova35,36,*, IN Subortseva27,*, MS Fominykh37,*, MV Frolova38,*, TV Shelekhova39,*, DG Sherstnev39,*, TV Shneider40,*, VA Shuvaev12,41,*, ZK Abdulkhalikova23,†, LV Anchukova38,†, IA Apanaskevich15,†, AN Arnautova22,†, MV Barabanshchikova23,†, NV Berlina34,†, AP Bityukov34,†, EA Gilyazitdinova27,†, VI Gilmanshina36,†, EK Egorova27,†, EV Efremova12,†, EB Zhalsanova31,†, EN Kabanova19,†, OB Kalashnikova20,†, AE Kersilova41,†, TI Kolosheinova27,†, PM Kondratovskii16,†, EV Koroleva28,†, AN Kotelnikova34,†, NA Lazareva16,†, NS Lazorko18,†, EV Lyyurova33,†, AS Lyamkina32,†, YuN Maslova20,†, ES Mileeva12,†, NE Mochkin3,†, EK Nekhai16,†, YaA Noskov13,†, ES Osipova29,†, MM Pankrashkina8,†, EV Potanina16,†, OD Rudenko25,†, TYu Rozhenkova36,†, EI Sbityakova18,†, NT Siordiya18,†, AV Talko16,†, EI Usacheva42,†, YuB Chernykh30,†, TV Chitanava18,†, KS Shashkina27,†, DI Shikhbabaeva8,†, KS Yurovskaya23,†

1 Saint Petersburg State University Hospital, 154 Fontanki nab., Saint Petersburg, Russian Federation, 198103

2 Multinational Center for Quality of Life Research, 1 Artilleriiskaya ul., Saint Petersburg, Russian Federation, 191014

3 NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya ul., Moscow, Russian Federation, 105203

4 Krai Clinical Hospital No. 1, 7 Kokhanskogo ul., Chita, Russian Federation, 672038

5 Yugry District Clinical Hospital, 40 Kalinina ul., Khanty-Mansiisk, Russian Federation, 628011

6 I Kant Baltic Federal University, 14 Aleksandra Nevskogo ul., Kaliningrad, Russian Federation, 236041

7 Clinical Hospital of Kaliningrad Region, 74 Klinicheskaya ul., Kaliningrad, Russian Federation, 236016

8 Moscow Municipal Center for Hematology, SP Botkin City Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284

9 NI Pirogov Russian National Research Medical University, 1 Ostrovityanova ul., Moscow, Russian Federation, 117997

10 Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela ul., Moscow, Russian Federation, 117997

11 Tula Regional Clinical Hospital, 1A korp. 1 Yablochkova ul., Tula, Russian Federation, 300053

12 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya ul., Saint Petersburg, Russian Federation, 191024

13 SM Kirov Military Medical Academy, 6 Akademika Lebedeva ul., Saint Petersburg, Russian Federation, 194044

14 II Mechnikov North-Western State Medical University, 47 Piskarevskii pr-t, Saint Petersburg, Russian Federation, 195067

15 SI Sergeev Krai Clinical Hospital No. 1, 9 Krasnodarskaya ul., Khabarovsk, Russian Federation, 680009

16 Krai Center of Hematology, Krai Clinical Hospital No. 2, 55 Russkaya ul., Vladivostok, Russian Federation, 690105

17 Ulyanovsk Regional Clinical Hospital, 7 III Internatsionala ul., Ulyanovsk, Russian Federation, 432017

18 VA Almazov National Medical Research Center, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341

19 Surgut District Clinical Hospital, 14 Energetikov ul., Surgut, Russian Federation, 628408

20 Clinical and Diagnostic Center, IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo ul., Saint Petersburg, Russian Federation, 197022

21 Volgograd Regional Clinical Oncology Dispensary, 78 Zemlyachki ul., Volgograd, Russian Federation, 400138

22 Lipetsk Municipal Hospital No. 3 “Svobodnyi sokol”, 10 Ushinskogo ul., Lipetsk, Russian Federation, 398007

23 RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov University, 12 Rentgena ul., Saint Petersburg, Russian Federation, 197022

24 Orenburg State Medical University, 6 Sovetskaya ul., Orenburg, Russian Federation, 460000

25 Orenburg Regional Clinical Hospital, 23 Aksakova ul., Orenburg, Russian Federation, 460018

26 Sakhalin Regional Clinical Hospital, 430 Mira pr-t, Yuzhno-Sakhalinsk, Russian Federation, 693004

27 National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

28 Regional Clinical Hospital, 105 Peterburgskoe sh., Tver, Russian Federation, 170036

29 Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya ul., Kirov, Russian Federation, 610027

30 MF Vladimirskii Moscow Regional Research Clinical Institute, 61/2 Shchepkina ul., Moscow, Russian Federation, 129110

31 NA Semashko Republican Clinical Hospital, 12 Pavlova ul., Ulan-Ude, Russian Federation, 670031

32 Novosibirsk State Medical University, 52 Krasnyi pr-t, Novosibirsk, Russian Federation, 630091

33 Komi Republican Oncology Dispensary, 46 Nyuvchimskoe sh., Syktyvkar, Republic of Komi, Russian Federation, 167904

34 NN Burdenko Main Military Clinical Hospital, 3 Gospital’naya pl., Moscow, Russian Federation, 105229

35 Bashkir State Medical University, 3 Lenina ul., Ufa, Republic of Bashkortostan, Russian Federation, 450008

36 GG Kuvatov Republican Clinical Hospital, 132 Dostoevskogo ul., Ufa, Republic of Bashkortostan, Russian Federation, 450005

37 Multispecialty Clinic “Skandinaviya”, AVA-PETER, 55A Liteinyi pr-t, Saint Petersburg, Russian Federation, 191014

38 Vologda Regional Clinical Hospital, 17 Lechebnaya ul., Vologda, Russian Federation, 160002

39 VI Razumovskii Saratov State Medical University, 6/9 53rd Strelkovoi Divizii ul., Saratov, Russian Federation, 410028

40 Leningrad Regional Clinical Hospital, 45 korp. 2A Lunacharskogo pr-t, Saint Petersburg, Russian Federation, 194291

41 VV Veresaev Municipal Clinical Hospital, 10 Lobnenskaya ul., Moscow, Russian Federation, 127644

42 SM Clinic, 19 korp. 1 Udarnikov pr-t, Saint Petersburg, Russian Federation, 195279

* Coordinators and members of Expert Panel.

Program participants.

For correspondence: Tatyana Pavlovna Nikitina, MD, PhD, 1 Artilleriiskaya ul., Saint Petersburg, Russian Federation, 191014; e-mail: qolife@mail.ru

For citation: Ionova TI, Andreevskaya EA, Babich EN, et al. Current Quality-of-Life Aspects in Patients with Classical Ph-Negative Myeloproliferative Neoplasms in the Russian Federation: Results and Discussion of the National Observational Program MPN-QoL-2020. Clinical oncohematology. 2022;15(2):176–97. (In Russ).

DOI: 10.21320/2500-2139-2022-15-2-176-197


ABSTRACT

Background. The National Observational Program MPN-QoL-2020 was aimed at collecting the data on QoL (quality of life) characteristics and symptoms as well as patient- and physician-related disease and treatment perceptions in classical Ph-negative myeloproliferative neoplasms (MPN) in the Russian Federation.

Aim. Using new standardized forms, to analyze the quality of life among patients with various MPNs, to characterize ubiquitous symptoms and their effect on quality of life among the myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET) patients as well as to describe the perceptions of disease- and therapy-associated problems as reported by patients and hematologists treating them.

Materials & Methods. The study enrolled 1100 patients with Ph-negative MPNs (355 MF, 408 PV, and 337 ET patients at the mean age of 58 ± 14 years, 61 % women). The study also involved 100 hematologists (mean age of 42 ± 12 years, 85 % women) from 37 health and preventive facilities in 8 Federal districts of the Russian Federation. The patients contributed to the study by one-time completing a special MPN10 form for MPN symptom assessment, a special QoL questionnaire HM-PRO for hematological malignancy patients, as well as a patient checklist. The task of hematologists consisted in one-time filling out of a physician checklist and completing the medical records of all the enrolled MPN patients.

Results. For the first time in the Russian Federation, the real clinical practice yielded the data on the quality of life in Ph-negative MPN patients, symptom profiles in different MPNs, and the extent of their effect on everyday life. QoL impairments mostly relate to physical and emotional functioning of MPN patients and to feeding and drinking regime, but rarely to social functioning. More than 1/3 of patients with Ph-negative MPNs reported on considerable QoL impairments. Absolute majority of patients complain of weakness: 92.6 % in MF, 83.7 % in PV, and 82 % in ET. The profiles of relevant symptoms and their intensity differ in various MPNs. The study identified the symptoms which need most to be corrected, both in the view of patients and physicians. There were established differences between patient- and doctor-reported evaluations of the attitude to the disease and treatment as well as the aspects for improvement in physician-patient relationship.

Conclusion. The National Observational Program MPN-QoL-2020 has resulted in characterization of QoL impairments in MPN patients in Russia. It determined the spectrum of particular disease and treatment challenges specific to these patients. Moreover, their unmet needs were updated. The outcomes of MPN-QoL-2020 can serve as a basis for the guidelines for QoL improvement/maintenance in Ph-negative MPNs and for activities aimed at raising MPN patients’ awareness about the disease and its treatment.

Keywords: classical Ph-negative myeloproliferative neoplasms, polycythemia vera, essential thrombocythemia, primary myelofibrosis, quality of life, MPN10 form.

Received: October 12, 2021

Accepted: February 10, 2022

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Статистика Plumx английский

REFERENCES

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Efficacy and Safety of Midostaurin Combined with Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia with FLT3 Mutation

SN Bondarenko1, AG Smirnova1, BI Ayubova1, EV Karyagina2, OS Uspenskaya3, YuS Neredko4, AP Kochergina5, IA Samorodova6, EA Pashneva7, YuS Chernykh8, YuA Dunaev9, NB Esef’eva10, RK Il’yasov11, TI Brazhkina12, IA Novokreshchenova13, ZK Simavonyan14, EI Kuzub15, VI Bakhtina16, TI Olkhovich17, MV Burundukova18, EV Babenko1, YuD Oleinikova1, IM Barkhatov1, TL Gindina1, IS Moiseev1, AD Kulagin1

1 RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo ul., Saint Petersburg, Russian Federation, 197022

2 Municipal Hospital No. 15, 4 Avangardnaya ul., Saint Petersburg, Russian Federation, 198205

3 Leningrad Regional Clinical Hospital, 45 korp. 2A Lunacharskogo pr-t, Saint Petersburg, Russian Federation, 194291

4 Stavropol Krai Clinical Oncology Dispensary, 182a Oktyabrskaya ul., Stavropol, Russian Federation, 355047

5 Krai Clinical Hospital, 1 Lyapidevskogo ul., Barnaul, Russian Federation, 656024

6 Municipal Clinical Hospital No. 31, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110

7 Volgograd Regional Clinical Oncology Dispensary, 78 Zemlyachki ul., Volgograd, Russian Federation, 400138

8 MF Vladimirskii Moscow Regional Research Clinical Institute, 61/2 Shchepkina ul., Moscow, Russian Federation, 129110

9 Arkhangelsk Regional Clinical Hospital, 292 Lomonosova pr-t, Arkhangelsk, Russian Federation, 163045

10 Ulyanovsk Regional Clinical Hospital, 7 III Internatsionala ul., Ulyanovsk, Russian Federation, 432017

11 VM Efetov Crimea Republican Clinical Oncology Dispensary, 49A Bespalova ul., Simferopol, Russian Federation, 295007

12 Ivanovo Regional Clinical Hospital, 1 Lyubimova ul., Ivanovo, Russian Federation, 153040

13 RZhD-Meditsina Clinical Hospital, 15 1-i Krasnoflotskii per., Smolensk, Russian Federation, 214025

14 AI Burnazyan Federal Medical Biophysical Center, 23 Marshala Novikova ul., Moscow, Russian Federation, 123098

15 Rostov State Medical University Hospital, 29 Nakhichevanskii per., Rostov-on-Don, Russian Federation, 344022

16 Krasnoyarsk Krai Clinical Hospital, 3A Partizana Zheleznyaka ul., Krasnoyarsk, Russian Federation, 660022

17 Krasnoyarsk Interdistrict Clinical Hospital No. 7, 4 Akademika Pavlova ul., Krasnoyarsk, Russian Federation, 660003

18 Municipal Clinical Hospital No. 2, 21 Polzunova ul., Novosibirsk, Russian Federation, 630051

For correspondence: Sergei Nikolaevich Bondarenko, MD, PhD, 6/8 L’va Tolstogo ul., Saint Petersburg, Russian Federation, 197022; Tel.: +7(921)994-35-70; e-mail: dr.sergeybondarenko@gmail.com

For citation: Bondarenko SN, Smirnova AG, Ayubova BI, et al. Efficacy and Safety of Midostaurin Combined with Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia with FLT3 Mutation. Clinical oncohematology. 2022;15(2):167–75. (In Russ).

DOI: 10.21320/2500-2139-2022-15-2-167-175


ABSTRACT

Background. The detection of FLT3-ITD mutation in acute myeloid leukemia (AML) patients is associated with poor prognosis and is an indication for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the first remission. Midostaurin is the first FLT3 inhibitor approved for the treatment of AML patients with FLT3 mutation in the Russian Federation in November 2019. This study deals with the initial experiences of using midostaurin in several centers for hematology in the Russian Federation.

Aim. To analyze the initial experiences of using midostaurin at different AML stages.

Materials & Methods. The study enrolled 42 patients with newly diagnosed AML with FLT3 mutation, who were treated with midostaurin combined with chemotherapy. Allo-HSCT was performed in 11 patients.

Results. The 2-year overall survival (OS) was 51 %, and the 2-year event-free survival (EFS) was 45 %. After achieving remission, the 2-year disease-free survival (DFS) was 58 %. The 1-year DFS of allo-HSCT recipients was 86 % (95% confidence interval [95% CI] 60–100 %) vs. 66 % in patients treated with chemotherapy without allo-HSCT (95% CI 34–98 %), respectively (= 0.5). Hyperleukocytosis at disease onset was associated with high relapse risk. Midostaurin had to be discontinued in 5 % of cases due to atrial fibrillation and QTc prolongation.

Conclusion. The present study demonstrates the safety and importance of including midostaurin in the regimens for treating AML with FLT3 mutation. Midostaurin assignment for maintenance therapy, after allo-HSCT as well as without performing it, can result in considerable improvement of OS and DFS.

Keywords: acute myeloid leukemias, FLT3 mutations, targeted therapy, midostaurin.

Received: December 27, 2021

Accepted: March 20, 2022

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REFERENCES

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Evaluation of Heterozygosity Loss in STR-Loci of Tumor DNA in Multiple Myeloma Patients with Plasmacytoma Based on the Molecular Analysis of Complex Archival Tumor Samples

EE Nikulina1, MV Firsova1, NV Risinskaya1, YaA Kozhevnikova2, MV Solov’ev1, TV Abramova1, TN Obukhova1, AM Kovrigina1, AB Sudarikov1, LP Mendeleeva1

1 National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

2 Faculty of Fundamental Medicine, MV Lomonosov Moscow State University, 27-1 Lomonosovskii pr-t, Moscow, Russian Federation, 119192

For correspondence: Elena Evgen’evna Nikulina, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: lenysh2007@rambler.ru

For citation: Nikulina EE, Firsova MV, Risinskaya NV, et al. Evaluation of Heterozygosity Loss in STR-Loci of Tumor DNA in Multiple Myeloma Patients with Plasmacytoma Based on the Molecular Analysis of Complex Archival Tumor Samples. Clinical oncohematology. 2022;15(2):156–66. (In Russ).

DOI: 10.21320/2500-2139-2022-15-2-156-166


ABSTRACT

Background. Multiple myeloma (MM) is a hematological malignancy with plasma cells as substrate. Sometimes MM is characterized by plasmacytomas, i.e., intra- and extraosseous tumors. A paraffin block containing plasmacytoma substrate provides valuable material to be used for analyzing the molecular biological characteristics of tumor. STR-profiling is a method for simultaneous evaluation of DNA degradation and integral assessment of tumor genome stability.

Aim. To describe STR-profiles of plasmacytoma DNA isolated from archival samples and to assess the integral stability of tumor genome against control DNA of patients.

Materials & Methods. The retrospective study enrolled 10 MM patients with plasmacytoma (7 women and 3 men) aged 34–62 years (median 53.5 years) who were treated at the National Research Center for Hematology from 2013 to 2021. Paired tumor/control DNA samples were obtained from all 10 patients.

Results. The present paper takes the first step in attempting a large-scale molecular genetic study of MM and provides first findings on the loss of heterozygosity (LOH) in plasmacytoma genome. All 10 patients showed LOH variants with different allelic loads having either deletion/quantitatively neutral LOH or duplication of one of the two alleles and involving 1–8 STR-loci. In plasmacytoma substrate the number of loci with LOH tended to be higher in the group with MM relapses compared with plasmacytomas identified at disease onset. According to the data analysis, LOH was frequently (in 4 out of 10 cases) detected on chromosomes 1 (1q42), 6 (6q14), 7 (7q21.11), 13 (13q31.1), and 21 (21q21.1).

Conclusion. The present paper shows the effectiveness of molecular analysis of DNAs being isolated from complex archival material consisting of paraffin blocks with plasmacytomas.

Keywords: multiple myeloma, plasmacytoma, loss of heterozygosity, STR-profiling.

Received: October 25, 2021

Accepted: January 28, 2022

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Статистика Plumx английский

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ROR-1 Expression in the Diagnosis and Monitoring of Minimal Residual Disease in Chronic Lymphocytic Leukemia

EV Pochtar1, SA Lugovskaya1, EV Naumova1, EA Dmitrieva2, VV Dolgov1

1 Russian Medical Academy of Postgraduate Education, 2/1 Barrikadnaya ul., Moscow, Russian Federation, 125993

2 SP Botkin City Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284

For correspondence: Evgenii Vladimirovich Pochtar, 12 apt. 53 Verkhnyaya Maslovka, Moscow, Russian Federation, 127083; Tel.: +7(917)550-06-38; e-mail: pochtar_ev@mail.ru

For citation: Pochtar EV, Lugovskaya SA, Naumova EV, et al. ROR-1 Expression in the Diagnosis and Monitoring of Minimal Residual Disease in Chronic Lymphocytic Leukemia. Clinical oncohematology. 2022;15(2):148–55. (In Russ).

DOI: 10.21320/2500-2139-2022-15-2-148-155


ABSTRACT

Background. In view of similar morphological and phenotypic characteristics of some B-cell lymphoproliferative diseases and despite the known phenotype of tumor cells, a search is currently underway for new diagnostic markers, the expression of which remains stable during chronic lymphocytic leukemia (CLL) treatment and can be used for both diagnosis and assessment of residual tumor population. One of such markers is ROR-1.

Aim. To assess the expression and feasibility of the ROR-1 marker using В-lymphocytes in minimal residual disease (MRD) dynamics and monitoring in CLL.

Materials & Methods. Hematological and immunophenotypic analyses were performed in 110 CLL patients (50 of them with newly diagnosed disease and 60 on therapy). In addition to that, 20 patients with reactive lymphocytosis and 32 donors were examined. The ROR-1 expression in В-lymphocytes were measured with FACS Canto II flow cytometer using the following monoclonal antibody panel: CD45, CD19, CD20, and ROR-1.

Results. The analysis showed that ROR-1 is essentially not expressed in normal and reactive В-lymphocytes and is detected in 100 % of CLL tumor cells both at disease onset and on therapy. The ROR-1 expression does not change during CLL treatment and can be used not only for CLL diagnosis but also for detection of MRD. Bone marrow aspirates (n = 64) and peripheral blood samples (n = 6) were analysed for MRD assessment by two methods: according to the standardized protocol, recommended by ERIC (European Research Initiative on CLL) in 2007, with FACS Canto II flow cytometer (BD Biosciences) and using DuraClone RE CLB Tube (Beckman Coulter) with Navious flow cytometer (Beckman Coulter).

Conclusion. The comparison of the two methods for MRD assessment, i.e., the standardized (ERIC) one and DuraClone RE CLB (Beckman Coulter) including ROR-1, yielded a high correlation between them (r = 0.9936.)

Keywords: ROR-1, chronic lymphocytic leukemia, minimal residual disease.

Received: December 27, 2021

Accepted: March 18, 2022

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Significance of the Expression of pAKT1 and pSyk Activation Proteins in Diffuse Large B-Cell Lymphoma

EV Vaneeva, VA Rosin, DA Dyakonov, SV Samarina, IV Paramonov

Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya ul., Kirov, Russian Federation, 610027

For correspondence: Elena Viktorovna Vaneeva, 72 Krasnoarmeiskaya ul., Kirov, Russian Federation, 610027; Tel.: +7(922)975-23-34; e-mail: vaneeva.elena.vic@mail.ru

For citation: Vaneeva EV, Rosin VA, Dyakonov DA, et al. Significance of the Expression of pAKT1 and pSyk Activation Proteins in Diffuse Large B-Cell Lymphoma. Clinical oncohematology. 2022;15(2):140–7. (In Russ).

DOI: 10.21320/2500-2139-2022-15-2-140-147


ABSTRACT

Aim. To assess the prognostic value of pAKT1 and рSyk expression in DLBCL.

Materials & Methods. The study enrolled 100 patients with newly diagnosed DLBCL treated with R-CHOP first-line immunochemotherapy. The relative count of pAKT1- and pSyk-expressing tumor cells was determined by immunohistochemical and morphometric methods. The expression cut-off of these proteins was calculated by ROC analysis. The relationship of protein expression with clinical parameters of DLBCL was analyzed by Fisher’s exact two-tailed test. The 5-year overall (OS) and progression-free (PFS) survivals were estimated by Kaplan-Meier method (log-rank test).

Results. High pAKT1 expression was associated with advanced DLBCL stages, International Prognostic Index > 2, serum lactate dehydrogenase concentration above normal, failures of R-CHOP therapy, as well as worse OS and PFS. No correlation between рSyk expression and clinical lymphoma characteristics was found. The worst 5-year OS (27.6 %) was reported in cases of pAKT1 and pSyk co-overexpression (hazard ratio [HR] 5.2; 95% confidence interval [95% CI] 2.49–10.9; < 0.001). A similar trend was observed for PFS (HR = 3.3; 95% CI 1.54–7.30; = 0.002).

Conclusion. Overexpression of pAKT1 is an informative indicator of a poor DLBCL prognosis. Co-overexpression of pAKT1 and рSyk markers is associated with worse OS and PFS compared to their isolated expressions and other co-expression variants.

Keywords: diffuse large B-cell lymphoma, pAKT1 and pSyk expression, overall survival, progression-free survival.

Received: November 17, 2021

Accepted: March 2, 2022

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REFERENCES

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Treatment of Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma: A Systematic Review and Meta-Analysis

AS Luchinin

Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya ul., Kirov, Russian Federation, 610027

For correspondence: Aleksander Sergeevich Luchinin, MD, PhD, 72 Krasnoarmeiskaya ul., Kirov, Russian Federation, 610027; Tel.: +7(919)506-87-86; e-mail: glivec@mail.ru

For citation: Luchinin AS. Treatment of Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma: A Systematic Review and Meta-Analysis. Clinical oncohematology. 2022;15(2):130–9. (In Russ).

DOI: 10.21320/2500-2139-2022-15-2-130-139


ABSTRACT

Background. Up to now, R-CHOP-21 therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) has been a standard option in the treatment of newly diagnosed diffuse large B-cell lymphoma (DLBCL). About 40–50 % of patients, however, show refractoriness to this therapy or develop early relapses.

Results. The outcomes of 22 clinical trials enrolling 9879 DLBCL patients were analyzed. The efficacies of different R-CHOP-21 therapy regimens were compared, and the progression-free-survivals were estimated. The network meta-analysis showed that, in the total cohort, the most effective first-line regimens were VenR-CHOP (hazard ratio [HR] 0.61; 95% confidence interval [95% CI] 0.37–1.00) and Pola-R-CHP (HR = 0.73; 95% CI 0.47–1.12). For non-GCB (ABC) subtype patients less than 60 years of age, R-ACVBP (HR = 0.31; 95% CI 0.12–0.79) and IR-CHOP (HR = 0.56; 95% CI 0.36–0.86) regimens appeared to be more effective than R-CHOP-21.

Conclusion. Today, the newly diagnosed DLBCL can be treated not only with R-CHOP-21, but also with alternative and more effective regimens. Their assignment, however, needs to be strictly personalized. IR-CHOP and R-ACVBP therapies can be administered in patients with non-GCB (ABC) subtype of DLBCL, if they are under 60 years of age. The list of these regimens can be further extended to include novel drugs, such as polatuzumab vedotin (its efficacy was confirmed by a randomized clinical trial) and venetoclax (its efficacy was confirmed by a non-randomized clinical trial).

Keywords: diffuse large B-cell lymphoma, meta-analysis.

Received: November 24, 2021

Accepted: March 7, 2022

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Статистика Plumx английский

REFERENCES

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Protocol ALL-IC BFM 2002: Outcomes of Pediatric Acute Lymphoblastic Leukemia Treatment under Multi-Center Clinical Trial

TT Valiev1, MA Shervashidze1, IV Osipova2, TI Burlutskaya3, NA Popova4, NS Osmulskaya5, GA Aleskerova6, SL Sabantsev7, ZS Gordeeva7, VYu Smirnov8, OA Poberezhnaya8, SN Yuldasheva9, IA Babich10, NA Batmanova1, SR Varfolomeeva1

1 Research Institute of Pediatric Oncology and Hematology, NN Blokhin National Medical Cancer Research Center, 23 Kashirskoye sh., Moscow, Russian Federation, 115478

2 Pediatric Republican Clinical Hospital of Tatarstan, 140 Orenburgskii trakt, Kazan, Russian Federation, 420138

3 Pediatric Regional Clinical Hospital, 44 Gubkina ul., Belgorod, Russian Federation, 308036

4 Volgograd Regional Clinical Oncology Dispensary, 78 Zemlyachki ul., Volgograd, Russian Federation, 400138

5 Regional Pediatric Clinical Hospital, 77 Kuibysheva ul., Omsk, Russian Federation, 644001

6 Azerbaijan National Center for Oncology, 79b G. Zardabi ul., Baku, Azerbaijan, AZ1011

7 LI Sokolova Ioshkar-Ola Pediatric Municipal Hospital, 104 Volkova ul., Ioshkar-Ola, Russian Federation, 424004

8 Kaluga Regional Clinical Pediatric Hospital, 1 Vishnevskogo ul., Kaluga, Russian Federation, 248007

9 VK Gusak Institute of Emergency and Reconstructive surgery, 47 Leninskii pr-t, Donetsk, Donetsk People’s Republic, 83003

10 Regional Pediatric Hospital, 311 Lenina ul., Yuzhno-Sakhalinsk, Russian Federation, 693006

For correspondence: Prof. Timur Teimurazovich Valiev, MD, PhD, 23 Kashirskoye sh., Moscow, Russian Federation, 115478; e-mail: timurvaliev@mail.ru

For citation: Valiev TT, Shervashidze MA, Osipova IV, et al. Protocol ALL-IC BFM 2002: Outcomes of Pediatric Acute Lymphoblastic Leukemia Treatment under Multi-Center Clinical Trial. Clinical oncohematology. 2022;15(2):119–29. (In Russ).

DOI: 10.21320/2500-2139-2022-15-2-119-129


ABSTRACT

Background. Programs of pediatric acute lymphoblastic leukemia (ALL) treatment, developed by the BFM (Berlin-Frankfurt-Munster) Group in 2002, remain one the most effective in the world. Long-term (10–15 years) overall survival in ALL children is above 90 %. Great progress in ALL treatment provided ground for including the ALL-IC BFM 2002 protocol into the Clinical Guidelines in 2020 (ID: 529).

Aim. To present the outcomes of ALL treatment in children according to ALL-IC BFM 2002 under the multi-center clinical trial.

Materials & Methods. From 01.11.2003 to 12.10.2021 the multi-center retrospective-prospective trial included 433 patients with newly diagnosed ALL, aged between 3 months and 21 years. The patients were aged from 0 to 12 (n = 344), from 12 to 18 (n = 70), and older than 12 years (n = 19). All of them were treated with ALL-IC BFM 2002. Overall (OS), disease-free (DFS), and event-free (EFS) survivals were estimated as of 01.12.2021.

Results. In the vast majority of patients (97.9 %, n = 424) complete clinical hematological remission was reached by Day 33 of the ALL-IC BFM 2002 treatment. The 10-year OS was 91.8 ± 1.5 %, DFS was 87.4 ± 1.8 %, and EFS was 84.1 ± 1.9 %. The 10-year OS in the groups of standard- and intermediate-risk patients was 92.8 ± 1.7 % and 94.6 ± 2.6 %, respectively, whereas in high-risk ALL relapse patients it was 71.1 ± 11.1 %.

Conclusion. The ALL-IC BFM 2002 protocol for treating pediatric ALL is reproducible in federal and regional clinics. The outcomes of the ALL-IC BFM 2002 treatment appeared to be impressive. They are comparable to those achieved in leading European and American clinics. To improve survival of high-risk patients, additional stratifying criteria are required, one of which should be the assessment of minimal residual disease (MRD). MRD detection became a basis for prognostic risk stratification under ALL-IC BFM 2009, the results of which will be presented in 2022–2023.

Keywords: acute lymphoblastic leukemia, treatment, ALL-IC BFM 2002, children.

Received: January 17, 2022

Accepted: March 25, 2022

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Статистика Plumx английский

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