title: Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute lymphoblastic leukaemia in first complete remission: comparison by genetic randomisation in an international prospective study.
abstract: BACKGROUND
  The dismal prognosis of very-high-risk childhood acute lymphoblastic leukaemia could be improved by allogeneic haemopoietic cell transplantation. We compared this strategy with intensified chemotherapy protocols, with the aim to improve the outcome of children with very-high-risk acute lymphoblastic leukaemia in first complete remission.
  
  
  METHODS
  A cooperative prospective study was set up in seven countries. Very-high-risk acute lymphoblastic leukaemia in first complete remission was defined by the presence of at least one of the following criteria: (1) failure to achieve complete remission after the first four-drug induction phase; (2) t(9;22) or t(4;11) clonal abnormalities; and (3) poor response to prednisone associated with T immunophenotype, white-blood-cell count of 100x10(9)/L or greater, or both. Children were allocated treatment by genetic chance, according to the availability of a compatible related donor, and assigned chemotherapy or haemopoietic-cell transplantation. The primary outcome was disease-free survival and analysis was by intention to treat.
  
  
  RESULTS
  Between April, 1995, and December, 2000, 357 children entered the study, of whom 280 were assigned chemotherapy and 77 related-donor haemopoietic-cell transplantation. 5-year disease-free survival was 40.6% (SE 3.1) in children allocated chemotherapy and 56.7% (5.7) in those assigned transplantation (hazard ratio 0.67 [95% CI 0.46-0.99]; p=0.02); 5-year survival was 50.1% (3.1) and 56.4% (5.9), respectively (0.73 [0.49-1.09]; p=0.12).
  
  
  CONCLUSIONS
  Children with very-high-risk acute lymphoblastic leukaemia benefit from related-donor haemopoietic-cell transplantation compared with chemotherapy. The gap between the two strategies increases as the risk profile of the patient worsens.
authors.affiliation: Clinica Pediatrica dell'Università degli Studi di Milano Bicocca, Ospedale San Gerardo Via Pergolesi 33, 20052 Monza, Milan, Italy. adriana.balduzzi@pediatriamonza.it
authors.forename: Adriana
authors.initials: A
authors.lastname: Balduzzi
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Valsecchi
authors.forename: Cornelio
authors.initials: C
authors.lastname: Uderzo
authors.forename: Paola
authors.initials: P
authors.lastname: De Lorenzo
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
authors.forename: Christina
authors.initials: C
authors.lastname: Peters
authors.forename: Jan
authors.initials: J
authors.lastname: Stary
authors.forename: Maria S
authors.initials: MS
authors.lastname: Felice
authors.forename: Edina
authors.initials: E
authors.lastname: Magyarosy
authors.forename: Valentino
authors.initials: V
authors.lastname: Conter
authors.forename: Alfred
authors.initials: A
authors.lastname: Reiter
authors.forename: Chiara
authors.initials: C
authors.lastname: Messina
authors.forename: Helmut
authors.initials: H
authors.lastname: Gadner
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D015996:Survival Rate; D014184:Transplantation, Homologous