Jan Stary1, Martin Zimmermann, Myriam Campbell, Luis Castillo, Eduardo Dibar, Svetlana Donska, Alejandro Gonzalez, Shai Izraeli, Dragana Janic, Janez Jazbec, Josip Konja, Emilia Kaiserova, Jerzy Kowalczyk, Gabor Kovacs, Chi-Kong Li, Edina Magyarosy, Alexander Popa, Batia Stark, Yahia Jabali, Jan Trka, Ondrej Hrusak, Hansjörg Riehm, Giuseppe Masera, Martin Schrappe. 1. Jan Stary, Jan Trka, and Ondrej Hrusak, Charles University and University Hospital Motol, Prague; Yahia Jabali, Regional Hospital, Ceske Budejovice, Czech Republic; Martin Zimmermann and Hansjörg Riehm, Medical School Hannover, Hannover; Martin Schrappe, University Hospital Schleswig-Holstein, Kiel, Germany; Myriam Campbell, Roberto del Rio Hospital, Universidad de Chile, Santiago, Chile; Luis Castillo, Hospital Pereira Rossell, Montevideo, Uruguay; Eduardo Dibar, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; Svetlana Donska, Regional Oncologic Hospital, Kiev, Ukraine; Alejandro Gonzalez, Institute of Hematology and Immunology, La Habana, Cuba; Shai Izraeli, Sheba Medical Center of Israel, Sackler School of Medicine, Tel Aviv University, Tel Hashomer; Batia Stark, Schneider Children's Medical Center of Israel, Sackler School of Medicine, Tel Aviv University, Petah-Tikva, Israel; Dragana Janic, University Children's Hospital, University of Belgrade, Belgrade, Serbia; Janez Jazbec, University Children's Hospital, Ljubljana, Slovenia; Josip Konja, University Hospital Centre Rebro, Zagreb, Croatia; Emilia Kaiserova, University Children's Hospital, Bratislava, Slovakia; Jerzy Kowalczyk, University of Lublin, Lublin, Poland; Gabor Kovacs and Edina Magyarosy, Semmelweis University, Budapest, Hungary; Chi-Kong Li, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region, People's Republic of China; Alexander Popa, N.N. Blokhin Russian Cancer Research Center, Moscow, Russia; and Giuseppe Masera, Ospedale S. Gerardo, University of Milano-Bicocca, Monza, Italy.
Abstract
PURPOSE: From 2002 to 2007, the International Berlin-Frankfurt-Münster Study Group conducted a prospective randomized clinical trial (ALL IC-BFM 2002) for the management of childhood acute lymphoblastic leukemia (ALL) in 15 countries on three continents. The aim of this trial was to explore the impact of differential delayed intensification (DI) on outcome in all risk groups. PATIENTS AND METHODS: For this trial, 5,060 eligible patients were divided into three risk groups according to age, WBC, early treatment response, and unfavorable genetic aberrations. DI was randomized as follows: standard risk (SR), two 4-week intensive elements (protocol III) versus one 7-week protocol II; intermediate risk (IR), protocol III × 3 versus protocol II × 1; high risk (HR), protocol III × 3 versus either protocol II × 2 (Associazione Italiana Ematologia Oncologia Pediatrica [AIEOP] option), or 3 HR blocks plus single protocol II (Berlin-Frankfurt-Münster [BFM] option). RESULTS: At 5 years, the probabilities of event-free survival and survival were 74% (± 1%) and 82% (± 1%) for all 5,060 eligible patients, 81% and 90% for the SR (n = 1,564), 75% and 83% for the IR (n = 2,650), and 55% and 62% for the HR (n = 846) groups, respectively. No improvement was accomplished by more intense and/or prolonged DI. CONCLUSION: The ALL IC-BFM 2002 trial is a good example of international collaboration in pediatric oncology. A wide platform of countries able to run randomized studies in ALL has been established. Although the alternative DI did not improve outcome compared with standard treatment and the overall results are worse than those achieved by longer established leukemia groups, the national results have generally improved.
RCT Entities:
PURPOSE: From 2002 to 2007, the International Berlin-Frankfurt-Münster Study Group conducted a prospective randomized clinical trial (ALL IC-BFM 2002) for the management of childhood acute lymphoblastic leukemia (ALL) in 15 countries on three continents. The aim of this trial was to explore the impact of differential delayed intensification (DI) on outcome in all risk groups. PATIENTS AND METHODS: For this trial, 5,060 eligible patients were divided into three risk groups according to age, WBC, early treatment response, and unfavorable genetic aberrations. DI was randomized as follows: standard risk (SR), two 4-week intensive elements (protocol III) versus one 7-week protocol II; intermediate risk (IR), protocol III × 3 versus protocol II × 1; high risk (HR), protocol III × 3 versus either protocol II × 2 (Associazione Italiana Ematologia Oncologia Pediatrica [AIEOP] option), or 3 HR blocks plus single protocol II (Berlin-Frankfurt-Münster [BFM] option). RESULTS: At 5 years, the probabilities of event-free survival and survival were 74% (± 1%) and 82% (± 1%) for all 5,060 eligible patients, 81% and 90% for the SR (n = 1,564), 75% and 83% for the IR (n = 2,650), and 55% and 62% for the HR (n = 846) groups, respectively. No improvement was accomplished by more intense and/or prolonged DI. CONCLUSION: The ALL IC-BFM 2002 trial is a good example of international collaboration in pediatric oncology. A wide platform of countries able to run randomized studies in ALL has been established. Although the alternative DI did not improve outcome compared with standard treatment and the overall results are worse than those achieved by longer established leukemia groups, the national results have generally improved.
Authors: A Karachunskiy; J Roumiantseva; S Lagoiko; C Bührer; G Tallen; O Aleinikova; O Bydanov; N Korepanova; L Bajdun; T Nasedkina; A von Stackelberg; G Novichkova; A Maschan; D Litvinov; N Myakova; N Ponomareva; K Kondratchik; L Fechina; O Streneva; N Judina; G Scharapova; A Shamardina; I Gerbek; A Shapochnik; A Rumjanzew; G Henze Journal: Leukemia Date: 2015-03-09 Impact factor: 11.528
Authors: Ao-Li Zhang; Xiao-Juan Chen; Yao Zou; Wen-Yu Yang; Ye Guo; Shu-Chun Wang; Li Zhang; Xiao-Ming Liu; Min Ruan; Tian-Feng Liu; Ben-Quan Qi; Xiao-Fan Zhu Journal: Zhongguo Dang Dai Er Ke Za Zhi Date: 2019-08