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

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.

• Timur Teimurazovich Valiev Research Institute of Pediatric Oncology and Hematology, NN Blokhin National Medical Cancer Research Center, 23 Kashirskoye sh., Moscow, Russian Federation, 115478 ; НИИ детской онкологии и гематологии, ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 23, Москва, Российская Федерация, 115478
• M.A. Shervashidze Research Institute of Pediatric Oncology and Hematology, NN Blokhin National Medical Cancer Research Center, 23 Kashirskoye sh., Moscow, Russian Federation, 115478 ; НИИ детской онкологии и гематологии, ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 23, Москва, Российская Федерация, 115478
• I.V. Osipova Pediatric Republican Clinical Hospital of Tatarstan, 140 Orenburgskii trakt, Kazan, Russian Federation, 420138 ; ГАУЗ «Детская республиканская клиническая больница Министерства здравоохранения Республики Татарстан», Оренбургский тракт, д. 140, Казань, Российская Федерация, 420138
• T.I. Burlutskaya Pediatric Regional Clinical Hospital, 44 Gubkina ul., Belgorod, Russian Federation, 308036 ; ОГБУЗ «Детская областная клиническая больница», ул. Губкина, д. 44, Белгород, Российская Федерация, 308036
• N.A. Popova Volgograd Regional Clinical Oncology Dispensary, 78 Zemlyachki ul., Volgograd, Russian Federation, 400138 ; ГБУЗ «Волгоградский областной клинический онкологический диспансер», ул. Землячки, д. 78, Волгоград, Российская Федерация, 400138
• N.S. Osmulskaya Regional Pediatric Clinical Hospital, 77 Kuibysheva ul., Omsk, Russian Federation, 644001 ; БУЗОО «Областная детская клиническая больница», ул. Куйбышева, д. 77, Омск, Российская Федерация, 644001
• G.A. Aleskerova Azerbaijan National Center for Oncology, 79b G. Zardabi ul., Baku, Azerbaijan, AZ1011 ; Национальный центр онкологии Республики Азербайджан, ул. Г. Зардаби, д. 79б, Баку, Республика Азербайджан, AZ1011
• S.L. Sabantsev LI Sokolova Ioshkar-Ola Pediatric Municipal Hospital, 104 Volkova ul., Ioshkar-Ola, Russian Federation, 424004 ; ГБУ РМЭ «Йошкар-Олинская детская городская больница им. Л.И. Соколовой», ул. Волкова, д. 104, Йошкар-Ола, Российская Федерация, 424004
• Z.S. Gordeeva LI Sokolova Ioshkar-Ola Pediatric Municipal Hospital, 104 Volkova ul., Ioshkar-Ola, Russian Federation, 424004 ; ГБУ РМЭ «Йошкар-Олинская детская городская больница им. Л.И. Соколовой», ул. Волкова, д. 104, Йошкар-Ола, Российская Федерация, 424004
• V.Yu. Smirnov Kaluga Regional Clinical Pediatric Hospital, 1 Vishnevskogo ul., Kaluga, Russian Federation, 248007 ; ГБУЗ «Калужская областная клиническая детская больница», ул. Вишневского, д. 1, Калуга, Российская Федерация, 248007
• O.A. Poberezhnaya Kaluga Regional Clinical Pediatric Hospital, 1 Vishnevskogo ul., Kaluga, Russian Federation, 248007 ; ГБУЗ «Калужская областная клиническая детская больница», ул. Вишневского, д. 1, Калуга, Российская Федерация, 248007
• S.N. Yuldasheva VK Gusak Institute of Emergency and Reconstructive surgery, 47 Leninskii pr-t, Donetsk, Donetsk People’s Republic, 83003 ; Институт неотложной и восстановительной хирургии им. В.К. Гусака, Ленинский пр-т, д. 47, Донецк, Донецкая Народная Республика, 83003
• I.A. Babich Regional Pediatric Hospital, 311 Lenina ul., Yuzhno-Sakhalinsk, Russian Federation, 693006 ; ГБУЗ «Областная детская больница», ул. Ленина, д. 311, Южно-Сахалинск, Российская Федерация, 693006
• N.A. Batmanova Research Institute of Pediatric Oncology and Hematology, NN Blokhin National Medical Cancer Research Center, 23 Kashirskoye sh., Moscow, Russian Federation, 115478 ; НИИ детской онкологии и гематологии, ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 23, Москва, Российская Федерация, 115478
• S.R. Varfolomeeva Research Institute of Pediatric Oncology and Hematology, NN Blokhin National Medical Cancer Research Center, 23 Kashirskoye sh., Moscow, Russian Federation, 115478 ; НИИ детской онкологии и гематологии, ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 23, Москва, Российская Федерация, 115478

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