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

AUTOIMMUNE THROMBOCYTOPENIA ,

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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