title: Intensive chemotherapy for childhood acute lymphoblastic leukemia: results of the randomized intercontinental trial ALL IC-BFM 2002.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Jan
authors.initials: J
authors.lastname: Stary
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Myriam
authors.initials: M
authors.lastname: Campbell
authors.forename: Luis
authors.initials: L
authors.lastname: Castillo
authors.forename: Eduardo
authors.initials: E
authors.lastname: Dibar
authors.forename: Svetlana
authors.initials: S
authors.lastname: Donska
authors.forename: Alejandro
authors.initials: A
authors.lastname: Gonzalez
authors.forename: Shai
authors.initials: S
authors.lastname: Izraeli
authors.forename: Dragana
authors.initials: D
authors.lastname: Janic
authors.forename: Janez
authors.initials: J
authors.lastname: Jazbec
authors.forename: Josip
authors.initials: J
authors.lastname: Konja
authors.forename: Emilia
authors.initials: E
authors.lastname: Kaiserova
authors.forename: Jerzy
authors.initials: J
authors.lastname: Kowalczyk
authors.forename: Gabor
authors.initials: G
authors.lastname: Kovacs
authors.forename: Chi-Kong
authors.initials: CK
authors.lastname: Li
authors.forename: Edina
authors.initials: E
authors.lastname: Magyarosy
authors.forename: Alexander
authors.initials: A
authors.lastname: Popa
authors.forename: Batia
authors.initials: B
authors.lastname: Stark
authors.forename: Yahia
authors.initials: Y
authors.lastname: Jabali
authors.forename: Jan
authors.initials: J
authors.lastname: Trka
authors.forename: Ondrej
authors.initials: O
authors.lastname: Hrusak
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Riehm
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Masera
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001208:Asia / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005060:Europe / Q000453:epidemiology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007391:International Cooperation; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000601:surgery; D011446:Prospective Studies; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D013020:South America / Q000453:epidemiology; D016896:Treatment Outcome